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BIOTECNOVA™
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KEYTRUDA® (pembrolizumab)
KEYTRUDA® (pembrolizumab)
KEYTRUDA® (pembrolizumab)
KEYTRUDA® (pembrolizumab)
KEYTRUDA® (pembrolizumab)
Merck Receives Positive EU CHMP Opinion for KEYTRUDA® (pembrolizumab) as Adjuvant Treatment for Adult and Adolescent (≥12 Years of Age) Patients With Stage IIB or IIC Melanoma Following Complete Resection
May 20, 2022 8:15 am ET
Opinion granted based on positive results from the Phase 3 KEYNOTE-716 trialIf approved, KEYTRUDA would be the first anti-PD-1 immunotherapy treatment option for patients 12 years and older in the EU across stage IIB, IIC and III melanoma following complete resection
RAHWAY, N.J.--(BUSINESS WIRE)-- Merck (NYSE: MRK), known as MSD outside the United States and Canada, today announced that the European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) adopted a positive opinion recommending approval of KEYTRUDA, Merck’s anti-PD-1 therapy, as monotherapy for the adjuvant treatment of adults and adolescents aged 12 years and older with stage IIB or IIC melanoma and who have undergone complete resection. Additionally, the CHMP recommended expanding the indications for KEYTRUDA in advanced (unresectable or metastatic) melanoma and stage III melanoma (as adjuvant treatment following complete resection) to include adolescent patients aged 12 years and older.“Based on the results of the KEYNOTE-716 trial, KEYTRUDA has shown a significant improvement in recurrence-free survival and distant metastasis-free survival for these patients with resected stage IIB or IIC melanoma,” said Dr. Scot Ebbinghaus, vice president, global clinical development, Merck Research Laboratories. “The CHMP’s positive recommendation brings us one step closer to providing patients 12 years and older in the European Union with a new option for resected stage IIB or IIC melanoma that can reduce the risk of their cancer returning.”The positive opinion was granted based on results from the Phase 3 KEYNOTE-716 trial, which demonstrated a statistically significant improvement in recurrence-free survival with KEYTRUDA compared to placebo (HR=0.65 [95% CI, 0.46-0.92]; p=0. 0.00658) in patients 12 years and older with stage IIB and IIC melanoma following complete resection. Earlier this year, Merck reported that KEYNOTE-716 also met its key secondary endpoint of distant metastasis-free survival. These results will be featured in a late-breaking oral presentation at the 2022 American Society of Clinical Oncology (ASCO) Annual Meeting on June 5 (Abstract #LBA9500).The CHMP’s recommendation will now be reviewed by the European Commission for marketing authorization in the European Union, and a final decision is expected in the second or third quarter of 2022.
About Merck’s research in melanoma
Melanoma, the most serious form of skin cancer, is characterized by the uncontrolled growth of pigment-producing cells. The rates of melanoma have been rising over the past few decades, with nearly 325,000 new cases of melanoma diagnosed worldwide in 2020, and melanoma is the leading cause of skin cancer deaths, with more than 57,000 deaths from the disease worldwide in 2020. In Europe, it is estimated there were more than 150,000 new cases of melanoma diagnosed and more than 26,000 deaths from the disease in 2020.The recurrence rates for resected melanoma are estimated to be 32-46% for patients with stage IIB and IIC disease and 39-74% for patients with stage III disease. The five-year survival rates are estimated to be 87% for stage IIB, 82% for stage IIC, 93% for stage IIIA, 83% for stage IIIB, 69% for stage IIIC and 32% for stage IIID.Merck is committed to delivering meaningful advances for patients with melanoma with KEYTRUDA and to continuing research in skin cancers through a broad clinical development program across investigational and approved medicines. KEYTRUDA has been established as an important treatment option for the adjuvant treatment of adult patients with resected stage III melanoma and is approved in over 90 countries based on the results from EORTC1325/KEYNOTE-054. KEYTRUDA is also approved worldwide for the treatment of patients with unresectable or metastatic melanoma.
About KEYTRUDA® (pembrolizumab) injection, 100 mg
KEYTRUDA is an anti-programmed death receptor-1 (PD-1) therapy that works by increasing the ability of the body’s immune system to help detect and fight tumor cells. KEYTRUDA is a humanized monoclonal antibody that blocks the interaction between PD-1 and its ligands, PD-L1 and PD-L2, thereby activating T lymphocytes which may affect both tumor cells and healthy cells.Merck has the industry’s largest immuno-oncology clinical research program. There are currently more than 1,700 trials studying KEYTRUDA across a wide variety of cancers and treatment settings. The KEYTRUDA clinical program seeks to understand the role of KEYTRUDA across cancers and the factors that may predict a patient's likelihood of benefitting from treatment with KEYTRUDA, including exploring several different biomarkers.
Selected KEYTRUDA® (pembrolizumab) Indications in the U.S.
MelanomaKEYTRUDA is indicated for the treatment of patients with unresectable or metastatic melanoma.KEYTRUDA is indicated for the adjuvant treatment of adult and pediatric (12 years and older) patients with stage IIB, IIC, or III melanoma following complete resection.See additional selected KEYTRUDA indications in the U.S. after the Selected Important Safety Information.
Selected Important Safety Information for KEYTRUDASevere and Fatal Immune-Mediated Adverse Reactions
KEYTRUDA is a monoclonal antibody that belongs to a class of drugs that bind to either the PD-1 or the PD-L1, blocking the PD-1/PD-L1 pathway, thereby removing inhibition of the immune response, potentially breaking peripheral tolerance and inducing immune-mediated adverse reactions. Immune-mediated adverse reactions, which may be severe or fatal, can occur in any organ system or tissue, can affect more than one body system simultaneously, and can occur at any time after starting treatment or after discontinuation of treatment. Important immune-mediated adverse reactions listed here may not include all possible severe and fatal immune-mediated adverse reactions.Monitor patients closely for symptoms and signs that may be clinical manifestations of underlying immune-mediated adverse reactions. Early identification and management are essential to ensure safe use of anti–PD-1/PD-L1 treatments. Evaluate liver enzymes, creatinine, and thyroid function at baseline and periodically during treatment. For patients with TNBC treated with KEYTRUDA in the neoadjuvant setting, monitor blood cortisol at baseline, prior to surgery, and as clinically indicated. In cases of suspected immune-mediated adverse reactions, initiate appropriate workup to exclude alternative etiologies, including infection. Institute medical management promptly, including specialty consultation as appropriate.Withhold or permanently discontinue KEYTRUDA depending on severity of the immune-mediated adverse reaction. In general, if KEYTRUDA requires interruption or discontinuation, administer systemic corticosteroid therapy (1 to 2 mg/kg/day prednisone or equivalent) until improvement to Grade 1 or less. Upon improvement to Grade 1 or less, initiate corticosteroid taper and continue to taper over at least 1 month. Consider administration of other systemic immunosuppressants in patients whose adverse reactions are not controlled with corticosteroid therapy.Immune-Mediated PneumonitisKEYTRUDA can cause immune-mediated pneumonitis. The incidence is higher in patients who have received prior thoracic radiation. Immune-mediated pneumonitis occurred in 3.4% (94/2799) of patients receiving KEYTRUDA, including fatal (0.1%), Grade 4 (0.3%), Grade 3 (0.9%), and Grade 2 (1.3%) reactions. Systemic corticosteroids were required in 67% (63/94) of patients. Pneumonitis led to permanent discontinuation of KEYTRUDA in 1.3% (36) and withholding in 0.9% (26) of patients. All patients who were withheld reinitiated KEYTRUDA after symptom improvement; of these, 23% had recurrence. Pneumonitis resolved in 59% of the 94 patients.Pneumonitis occurred in 8% (31/389) of adult patients with cHL receiving KEYTRUDA as a single agent, including Grades 3-4 in 2.3% of patients. Patients received high-dose corticosteroids for a median duration of 10 days (range: 2 days to 53 months). Pneumonitis rates were similar in patients with and without prior thoracic radiation. Pneumonitis led to discontinuation of KEYTRUDA in 5.4% (21) of patients. Of the patients who developed pneumonitis, 42% interrupted KEYTRUDA, 68% discontinued KEYTRUDA, and 77% had resolution.Immune-Mediated ColitisKEYTRUDA can cause immune-mediated colitis, which may present with diarrhea. Cytomegalovirus infection/reactivation has been reported in patients with corticosteroid-refractory immune-mediated colitis. In cases of corticosteroid-refractory colitis, consider repeating infectious workup to exclude alternative etiologies. Immune-mediated colitis occurred in 1.7% (48/2799) of patients receiving KEYTRUDA, including Grade 4 (<0.1%), Grade 3 (1.1%), and Grade 2 (0.4%) reactions. Systemic corticosteroids were required in 69% (33/48); additional immunosuppressant therapy was required in 4.2% of patients. Colitis led to permanent discontinuation of KEYTRUDA in 0.5% (15) and withholding in 0.5% (13) of patients. All patients who were withheld reinitiated KEYTRUDA after symptom improvement; of these, 23% had recurrence. Colitis resolved in 85% of the 48 patients.Hepatotoxicity and Immune-Mediated HepatitisKEYTRUDA as a Single AgentKEYTRUDA can cause immune-mediated hepatitis. Immune-mediated hepatitis occurred in 0.7% (19/2799) of patients receiving KEYTRUDA, including Grade 4 (<0.1%), Grade 3 (0.4%), and Grade 2 (0.1%) reactions. Systemic corticosteroids were required in 68% (13/19) of patients; additional immunosuppressant therapy was required in 11% of patients. Hepatitis led to permanent discontinuation of KEYTRUDA in 0.2% (6) and withholding in 0.3% (9) of patients. All patients who were withheld reinitiated KEYTRUDA after symptom improvement; of these, none had recurrence. Hepatitis resolved in 79% of the 19 patients.KEYTRUDA With AxitinibKEYTRUDA in combination with axitinib can cause hepatic toxicity. Monitor liver enzymes before initiation of and periodically throughout treatment. Consider monitoring more frequently as compared to when the drugs are administered as single agents. For elevated liver enzymes, interrupt KEYTRUDA and axitinib, and consider administering corticosteroids as needed. With the combination of KEYTRUDA and axitinib, Grades 3 and 4 increased alanine aminotransferase (ALT) (20%) and increased aspartate aminotransferase (AST) (13%) were seen at a higher frequency compared to KEYTRUDA alone. Fifty-nine percent of the patients with increased ALT received systemic corticosteroids. In patients with ALT ≥3 times upper limit of normal (ULN) (Grades 2-4, n=116), ALT resolved to Grades 0-1 in 94%. Among the 92 patients who were rechallenged with either KEYTRUDA (n=3) or axitinib (n=34) administered as a single agent or with both (n=55), recurrence of ALT ≥3 times ULN was observed in 1 patient receiving KEYTRUDA, 16 patients receiving axitinib, and 24 patients receiving both. All patients with a recurrence of ALT ≥3 ULN subsequently recovered from the event.Immune-Mediated EndocrinopathiesAdrenal InsufficiencyKEYTRUDA can cause primary or secondary adrenal insufficiency. For Grade 2 or higher, initiate symptomatic treatment, including hormone replacement as clinically indicated. Withhold KEYTRUDA depending on severity. Adrenal insufficiency occurred in 0.8% (22/2799) of patients receiving KEYTRUDA, including Grade 4 (<0.1%), Grade 3 (0.3%), and Grade 2 (0.3%) reactions. Systemic corticosteroids were required in 77% (17/22) of patients; of these, the majority remained on systemic corticosteroids. Adrenal insufficiency led to permanent discontinuation of KEYTRUDA in <0.1% (1) and withholding in 0.3% (8) of patients. All patients who were withheld reinitiated KEYTRUDA after symptom improvement.HypophysitisKEYTRUDA can cause immune-mediated hypophysitis. Hypophysitis can present with acute symptoms associated with mass effect such as headache, photophobia, or visual field defects. Hypophysitis can cause hypopituitarism. Initiate hormone replacement as indicated. Withhold or permanently discontinue KEYTRUDA depending on severity. Hypophysitis occurred in 0.6% (17/2799) of patients receiving KEYTRUDA, including Grade 4 (<0.1%), Grade 3 (0.3%), and Grade 2 (0.2%) reactions. Systemic corticosteroids were required in 94% (16/17) of patients; of these, the majority remained on systemic corticosteroids. Hypophysitis led to permanent discontinuation of KEYTRUDA in 0.1% (4) and withholding in 0.3% (7) of patients. All patients who were withheld reinitiated KEYTRUDA after symptom improvement.Thyroid DisordersKEYTRUDA can cause immune-mediated thyroid disorders. Thyroiditis can present with or without endocrinopathy. Hypothyroidism can follow hyperthyroidism. Initiate hormone replacement for hypothyroidism or institute medical management of hyperthyroidism as clinically indicated. Withhold or permanently discontinue KEYTRUDA depending on severity. Thyroiditis occurred in 0.6% (16/2799) of patients receiving KEYTRUDA, including Grade 2 (0.3%). None discontinued, but KEYTRUDA was withheld in <0.1% (1) of patients.Hyperthyroidism occurred in 3.4% (96/2799) of patients receiving KEYTRUDA, including Grade 3 (0.1%) and Grade 2 (0.8%). It led to permanent discontinuation of KEYTRUDA in <0.1% (2) and withholding in 0.3% (7) of patients. All patients who were withheld reinitiated KEYTRUDA after symptom improvement. Hypothyroidism occurred in 8% (237/2799) of patients receiving KEYTRUDA, including Grade 3 (0.1%) and Grade 2 (6.2%). It led to permanent discontinuation of KEYTRUDA in <0.1% (1) and withholding in 0.5% (14) of patients. All patients who were withheld reinitiated KEYTRUDA after symptom improvement. The majority of patients with hypothyroidism required long-term thyroid hormone replacement. The incidence of new or worsening hypothyroidism was higher in 1185 patients with HNSCC, occurring in 16% of patients receiving KEYTRUDA as a single agent or in combination with platinum and FU, including Grade 3 (0.3%) hypothyroidism. The incidence of new or worsening hypothyroidism was higher in 389 adult patients with cHL (17%) receiving KEYTRUDA as a single agent, including Grade 1 (6.2%) and Grade 2 (10.8%) hypothyroidism.Type 1 Diabetes Mellitus (DM), Which Can Present With Diabetic KetoacidosisMonitor patients for hyperglycemia or other signs and symptoms of diabetes. Initiate treatment with insulin as clinically indicated. Withhold KEYTRUDA depending on severity. Type 1 DM occurred in 0.2% (6/2799) of patients receiving KEYTRUDA. It led to permanent discontinuation in <0.1% (1) and withholding of KEYTRUDA in <0.1% (1) of patients. All patients who were withheld reinitiated KEYTRUDA after symptom improvement.Immune-Mediated Nephritis With Renal DysfunctionKEYTRUDA can cause immune-mediated nephritis. Immune-mediated nephritis occurred in 0.3% (9/2799) of patients receiving KEYTRUDA, including Grade 4 (<0.1%), Grade 3 (0.1%), and Grade 2 (0.1%) reactions. Systemic corticosteroids were required in 89% (8/9) of patients. Nephritis led to permanent discontinuation of KEYTRUDA in 0.1% (3) and withholding in 0.1% (3) of patients. All patients who were withheld reinitiated KEYTRUDA after symptom improvement; of these, none had recurrence. Nephritis resolved in 56% of the 9 patients.Immune-Mediated Dermatologic Adverse ReactionsKEYTRUDA can cause immune-mediated rash or dermatitis. Exfoliative dermatitis, including Stevens-Johnson syndrome, drug rash with eosinophilia and systemic symptoms, and toxic epidermal necrolysis, has occurred with anti–PD-1/PD-L1 treatments. Topical emollients and/or topical corticosteroids may be adequate to treat mild to moderate nonexfoliative rashes. Withhold or permanently discontinue KEYTRUDA depending on severity. Immune-mediated dermatologic adverse reactions occurred in 1.4% (38/2799) of patients receiving KEYTRUDA, including Grade 3 (1%) and Grade 2 (0.1%) reactions. Systemic corticosteroids were required in 40% (15/38) of patients. These reactions led to permanent discontinuation in 0.1% (2) and withholding of KEYTRUDA in 0.6% (16) of patients. All patients who were withheld reinitiated KEYTRUDA after symptom improvement; of these, 6% had recurrence. The reactions resolved in 79% of the 38 patients.Other Immune-Mediated Adverse ReactionsThe following clinically significant immune-mediated adverse reactions occurred at an incidence of <1% (unless otherwise noted) in patients who received KEYTRUDA or were reported with the use of other anti–PD-1/PD-L1 treatments. Severe or fatal cases have been reported for some of these adverse reactions. Cardiac/Vascular: Myocarditis, pericarditis, vasculitis; Nervous System: Meningitis, encephalitis, myelitis and demyelination, myasthenic syndrome/myasthenia gravis (including exacerbation), Guillain-Barré syndrome, nerve paresis, autoimmune neuropathy; Ocular: Uveitis, iritis and other ocular inflammatory toxicities can occur. Some cases can be associated with retinal detachment. Various grades of visual impairment, including blindness, can occur. If uveitis occurs in combination with other immune-mediated adverse reactions, consider a Vogt-Koyanagi-Harada-like syndrome, as this may require treatment with systemic steroids to reduce the risk of permanent vision loss; Gastrointestinal: Pancreatitis, to include increases in serum amylase and lipase levels, gastritis, duodenitis; Musculoskeletal and Connective Tissue: Myositis/polymyositis, rhabdomyolysis (and associated sequelae, including renal failure), arthritis (1.5%), polymyalgia rheumatica; Endocrine: Hypoparathyroidism; Hematologic/Immune: Hemolytic anemia, aplastic anemia, hemophagocytic lymphohistiocytosis, systemic inflammatory response syndrome, histiocytic necrotizing lymphadenitis (Kikuchi lymphadenitis), sarcoidosis, immune thrombocytopenic purpura, solid organ transplant rejection.
https://www.keytruda.com/
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Please see Prescribing Information for KEYTRUDA (pembrolizumab) at http://www.merck.com/product/usa/pi_circulars/k/keytruda/keytruda_pi.pdf and Medication Guide for KEYTRUDA at http://www.merck.com/product/usa/pi_circulars/k/keytruda/keytruda_mg.pdf. Source: Merck & Co., Inc.
Merck's blockbuster Keytruda gets EMA panel nod for expanded use in skin cancer
May 20, 2022 9:20 AM ET
By: Ravikash, SA News Editor A committee of the European Medicines Agency (EMA) recommended the approval for expanded use of Merck's (NYSE:MRK) blockbuster drug Keytruda in certain patients with a type of skin cancer called melanoma
https://seekingalpha.com/symbol/MRK
Farxiga (dapagliflozin)
ENHERTU® (fam-trastuzumab deruxtecan-nxki)
KEYTRUDA® (pembrolizumab)
Farxiga met primary endpoint in DELIVER Phase III trial, reducing risk of cardiovascular death or worsening heart failure in patients with preserved ejection fraction
PUBLISHED5 May 2022
5 May 2022 07:05 BST
Results from the DELIVER and DAPA-HF Phase III trials demonstrate Farxiga’s efficacy in heart failure regardless of ejection fraction
High-level results from the DELIVER Phase III trial showed AstraZeneca’s Farxiga (dapagliflozin) reached a statistically significant and clinically meaningful reduction in the primary composite endpoint of cardiovascular (CV) death or worsening heart failure (HF). The trial was conducted in patients with HF with mildly reduced or preserved ejection fraction (defined as left ventricular ejection fraction [LVEF] greater than 40%).HF is a chronic, long-term condition that worsens over time1. It affects nearly 64 million people globally2 and is associated with substantial morbidity and mortality3. There are several main categories of HF related to ejection fraction (EF), a measurement of the percentage of blood leaving the heart each time it contracts including: HF with reduced EF (HFrEF) (LVEF less than or equal to 40%), HF with mildly reduced EF (HFmrEF) (LVEF 41-49%) and preserved EF (HFpEF) (LVEF greater than or equal to 50%)4. Approximately half of all HF patients have mildly reduced or preserved EF with few therapeutic options available4,5. Farxiga already has approved indications relating to the treatment of type-2 diabetes (T2D), HFrEF and chronic kidney disease (CKD). Dr. Scott Solomon, Professor of Medicine at Harvard Medical School and Brigham and Women’s Hospital and Principal Investigator of the DELIVER Phase III trial, said: “We are delighted to have met the primary endpoint in this patient population which has few treatment options. DELIVER is the largest and broadest trial to date in heart failure with mildly reduced or preserved ejection fraction. The results of DELIVER extend the benefit of dapagliflozin to the full spectrum of patients with heart failure.”Mene Pangalos, Executive Vice President, BioPharmaceuticals R&D, AstraZeneca, said: "Today’s groundbreaking results coupled with those from the DAPA-HF trial show that Farxiga is effective in treating heart failure regardless of ejection fraction. These data build upon our previous studies demonstrating cardiorenal protection across patients with either diabetes, chronic kidney disease or heart failure.”The safety and tolerability profile of Farxiga in the DELIVER Phase III trial were consistent with the well-established safety profile of the medicine.The full DELIVER Phase III trial results will be submitted for presentation at a forthcoming medical meeting and regulatory submissions will be made in the coming months. DELIVERDELIVER was an international, randomised, double-blind, parallel-group, placebo-controlled, event-driven Phase III trial designed to evaluate the efficacy of Farxiga, compared with placebo, in the treatment of HF patients with LVEF greater than 40% with or without T2D. Farxiga was given once daily in addition to background therapy (regional standard of care for all comorbidities, including diabetes and hypertension, with the exception of concomitant use of a sodium-glucose cotransporter 2 [SGLT2] inhibitor)13. DELIVER is the largest clinical trial to date in HF patients with EF above 40%, with 6,263 randomised patients13,14.The primary endpoint was the time to first occurrence of CV death, hospitalisation for HF (hHF) or an urgent HF visit. The secondary endpoint includes the total number of HF events (hHF or urgent HF visit) and CV death, change from baseline in the total symptom score of the Kansas City Cardiomyopathy Questionnaire at eight months, time to the occurrence of CV death and time to the occurrence of death from any cause13.Farxiga Farxiga (dapagliflozin) is a first-in-class, oral, once-daily SGLT2 inhibitor. Research has shown Farxiga’s efficacy in preventing and delaying cardiorenal disease, while also protecting the organs – important findings given the underlying links between the heart, kidneys and pancreas15-17. Damage to one of these organs can cause the other organs to fail, contributing to leading causes of death worldwide, including T2D, HF and CKD2,18-20.In the US, Farxiga is approved as an adjunct to diet and exercise to improve glycaemic control in adults with T2D and in T2D to reduce the risk of hHF or CV death when added to standard of care based on the findings of the DECLARE-TIMI 58 Phase III CV outcomes trial17. Farxiga is also approved for the treatment of HFrEF and the treatment of CKD based on the findings of the DAPA-HF and DAPA-CKD Phase III trials. In the European Union, Forxiga is indicated as both monotherapy (when metformin is appropriate) and as part of combination therapy for the treatment of insufficiently controlled T2D, with the additional benefits of weight loss and blood-pressure reduction, as an adjunct to diet and exercise in adults with T2D. Forxiga is also approved for the treatment of symptomatic chronic HFrEF in adults with and without T2D and for the treatment of CKD in adults with and without T2D.DapaCare is a robust programme of clinical trials to evaluate the potential CV, renal and organ protection benefits of Farxiga. It includes more than 35 completed and ongoing Phase IIb/III trials in more than 35,000 patients, as well as more than 2.5 million patient-years’ experience. Farxiga is currently being tested in the DAPA-MI Phase III trial - a first of its kind, indication-seeking registry-based randomised controlled trial in patients without T2D following an acute myocardial infarction (MI) or heart attack21.https://www.farxiga.com/
Please visit astrazeneca.com and follow the Company on Twitter @AstraZeneca.
AstraZeneca Farxiga cuts risk of death/heart failure in certain patients in late-stage study
May 05, 2022 7:57 AM ETAstraZeneca PLC (AZN)By: Ravikash, SA News Editor AstraZeneca (NASDAQ:AZN) said data from a late-stage study showed that its drug Farxiga helped reduce the risk of death or heart failure (HF) in certain patients.https://seekingalpha.com/news/3833244-astrazeneca-farxiga-cuts-risk-of-deathheart-failure-in-certain-patients-in-late-stage-studyhttps://seekingalpha.com/symbol/AZNhttps://www.astrazeneca.com/https://www.farxiga.com/
ENHERTU® (fam-trastuzumab deruxtecan-nxki)
ENHERTU® (fam-trastuzumab deruxtecan-nxki)
ENHERTU® (fam-trastuzumab deruxtecan-nxki)
Enhertu approved in the US for patients with HER2-positive metastatic breast cancer treated with a prior anti-HER2-based regimen
PUBLISHED5 May 2022
5 May 2022 07:10 BST
Approval broadens indication for AstraZeneca and Daiichi Sankyo’s Enhertu to earlier use in metastatic breast cancer
Based on ground-breaking DESTINY-Breast03 results showing Enhertu reduced the risk of disease progression or death by 72% versus trastuzumab emtansine (T-DM1)
AstraZeneca and Daiichi Sankyo’s Enhertu (trastuzumab deruxtecan) has been approved in the US for the treatment of adult patients with unresectable or metastatic HER2-positive breast cancer who have received a prior anti-HER2-based regimen either in the metastatic setting, or in the neoadjuvant or adjuvant setting and have developed disease recurrence during or within six months of completing therapy.
Enhertu is a specifically engineered HER2-directed antibody drug conjugate (ADC) being jointly developed and commercialised by AstraZeneca and Daiichi Sankyo.
The approval by the Food and Drug Administration (FDA) was based on positive results from the DESTINY-Breast03 Phase III trial that showed Enhertu reduced the risk of disease progression or death by 72% versus trastuzumab emtansine (T-DM1) (hazard ratio [HR] 0.28; 95% confidence interval [CI]: 0.22-0.37; p<0.0001) in patients with HER2-positive unresectable and/or metastatic breast cancer previously treated with trastuzumab and a taxane.
The approval was granted under the FDA’s Real-Time Oncology Review (RTOR) programme and converts the accelerated approval of Enhertu in later line HER2-positive metastatic breast cancer to standard approval, broadening Enhertu’s breast cancer indication in the US to earlier lines of use in patients with HER2-positive metastatic breast cancer.
Erika Hamilton, MD, Director of the Breast Cancer and Gynecological Cancer Research Program for Sarah Cannon Research Institute, Nashville, Tennessee, US, said: “Enhertu has demonstrated significant progression-free survival in the earlier metastatic setting, potentially establishing it as a new standard of care in previously treated patients with HER2-positive metastatic breast cancer. Today’s approval is an important milestone for the clinical community as we will now be able to offer Enhertu to these patients earlier in their treatment.”
Catherine Ormerod, Executive Vice President, Strategy and Mission, Living Beyond Breast Cancer, said: “This is an important day for the breast cancer community. With this approval, Enhertu now provides a new treatment option for patients with HER2-positive metastatic breast cancer which can be used earlier in treatment to potentially delay progression of disease.”
Dave Fredrickson, Executive Vice President, Oncology Business Unit, AstraZeneca, said: “Enhertu is already established in the later-line treatment of patients with HER2-positive metastatic breast cancer, and we are thrilled that with this approval, patients in the US will now be able to access the transformative potential of Enhertu earlier in their treatment. We look forward to bringing this important, potentially paradigm-shifting medicine to even more patients across the globe in an earlier setting as quickly as possible.”
Ken Keller, Global Head, Oncology Business and President and CEO, Daiichi Sankyo, Inc, said: “Today’s FDA approval, which converts the accelerated approval of Enhertu to regular approval, highlights the importance of the FDA’s accelerated pathway that allows for earlier approval of medicines to treat serious medical conditions such as breast cancer. Data from DESTINY-Breast03 not only confirmed the results of DESTINY-Breast01, but also demonstrated the superiority of Enhertu in prolonging progression-free survival compared to T-DM1 in an earlier setting of HER2-positive metastatic breast cancer.”
The DESTINY-Breast03 Phase III trial results were recently published online in The New England Journal of Medicine.1 In the trial, the safety profile of Enhertu was consistent with previous clinical trials, with no new safety concerns identified and no Grade 4 or 5 treatment-related interstitial lung disease events.
Based on the DESTINY-Breast03 data, fam-trastuzumab deruxtecan-nxki (Enhertu) recently was added to the NCCN Clinical Practical Guidelines in Oncology (NCCN Guidelines®) as the Category 1 preferred regimen as second-line therapy for recurrent unresectable (local or regional) or Stage IV HER2-positive disease.2
The US regulatory submission was reviewed under Project Orbis, which provides a framework for concurrent submission and review of oncology medicines among participating international partners. Five national health authorities collaborated with the FDA on this review, including the Australian Therapeutic Goods Administration, the Brazilian Health Regulatory Agency (ANVISA), Health Canada, Israel’s Ministry of Health Pharmaceutical Administration and Switzerland’s Swissmedic.
This approval follows the recent Priority Review and Breakthrough Therapy Designation of Enhertu in the US in this earlier setting.
Regulatory applications for Enhertu are currently under review in Europe, Japan and several other countries for the treatment of adult patients with unresectable or metastatic HER2-positive breast cancer who have received a prior anti-HER2-based regimen based on the results from the DESTINY-Breast03 trial.
DESTINY-Breast03
DESTINY-Breast03 is a global, head-to-head, randomised, open-label, registrational Phase III trial evaluating the efficacy and safety of Enhertu (5.4mg/kg) versus T-DM1 in patients with HER2-positive unresectable and/or metastatic breast cancer previously treated with trastuzumab and a taxane.
The primary efficacy endpoint of DESTINY-Breast03 is progression-free survival (PFS) based on blinded independent central review. Secondary efficacy endpoints include overall survival, objective response rate (ORR), duration of response, PFS based on investigator assessment and safety.
DESTINY-Breast03 enrolled approximately 500 patients at multiple sites in Asia, Europe, North America, Oceania and South America. For more information about the trial, visit ClinicalTrials.gov.
Enhertu
Enhertu is a HER2-directed ADC. Designed using Daiichi Sankyo’s proprietary DXd ADC technology, Enhertu is the lead ADC in the oncology portfolio of Daiichi Sankyo and the most advanced programme in AstraZeneca’s ADC scientific platform. Enhertu consists of a HER2 monoclonal antibody attached to a topoisomerase I inhibitor payload, an exatecan derivative, via a stable tetrapeptide-based cleavable linker.
Enhertu (5.4mg/kg) is approved in the US for the treatment of adult patients with unresectable or metastatic HER2-positive breast cancer who have received a prior anti-HER2-based regimen either in the metastatic setting, or in the neoadjuvant or adjuvant setting and have developed disease recurrence during or within six months of completing therapy, based on results from the DESTINY-Breast03 trial.
Enhertu (5.4mg/kg) is also approved in approximately 40 countries for the treatment of adult patients with unresectable or metastatic HER2-positive breast cancer who have received two or more prior anti-HER2-based regimens based on the results from the DESTINY-Breast01 trial.
Enhertu (6.4mg/kg) is approved in several countries for the treatment of adult patients with locally advanced or metastatic HER2-positive gastric or gastroesophageal junction adenocarcinoma who have received a prior trastuzumab-based regimen based on the results from the DESTINY-Gastric01 trial.
Enhertu development programme
A comprehensive development programme is underway globally, evaluating the efficacy and safety of Enhertu monotherapy across multiple HER2-targetable cancers, including breast, gastric, lung and colorectal cancers. Trials in combination with other anticancer treatments, such as immunotherapy, are also underway.
Regulatory applications for Enhertu are currently under review in Europe, Japan and several other countries for the treatment of adult patients with unresectable or metastatic HER2-positive breast cancer who have received a prior anti-HER2 based regimen based on the results from the DESTINY-Breast03 trial.
Enhertu was granted Breakthrough Therapy Designation in the US for the treatment of adult patients with unresectable or metastatic HER2-low (IHC 1+ or IHC 2+/ISH-negative) breast cancer who have received a prior systemic therapy in the metastatic setting or developed disease recurrence during or within six months of completing adjuvant chemotherapy, based on the results of the DESTINY-Breast04 trial. Patients with hormone receptor (HR) positive breast cancer should additionally have received or be ineligible for endocrine therapy.
Enhertu is also currently under review in the US for the treatment of adult patients with unresectable or metastatic non-small cell lung cancer (NSCLC) whose tumours have a HER2 (ERBB2) mutation and who have received a prior systemic therapy, based on the DESTINY-Lung01 trial, and in Europe for the treatment of adult patients with locally advanced or metastatic HER2-positive gastric or GEJ adenocarcinoma who have received a prior anti-HER2-based regimen based on the DESTINY-Gastric01 and DESTINY-Gastric02 trials.
Daiichi Sankyo collaboration
Daiichi Sankyo Company, Limited (TSE:4568) [referred to as Daiichi Sankyo] and AstraZeneca entered into a global collaboration to jointly develop and commercialise Enhertu (a HER2-directed ADC) in March 2019, and datopotamab deruxtecan (DS-1062; a TROP2-directed ADC) in July 2020, except in Japan where Daiichi Sankyo maintains exclusive rights. Daiichi Sankyo is responsible for manufacturing and supply of Enhertu and datopotamab deruxtecan.
Please visit astrazeneca.com and follow the Company on Twitter @AstraZeneca.
AstraZeneca, Daiichi Sankyo's Enhertu wins FDA approval to treat breast cancer subtype
May 05, 2022 4:48 AM ET
AstraZeneca PLC (AZN), DSNKYDSKYF
By: Ravikash, SA News Editor1 Comment
The U.S. Food and Drug Administration (FDA) approved AstraZeneca (NASDAQ:AZN) and Daiichi Sankyo's (OTCPK:DSKYF) (OTCPK:DSNKY) Enhertu to treat certain patients with breast cancer.
https://seekingalpha.com/symbol/DSKYF
https://seekingalpha.com/symbol/DSNKY
https://seekingalpha.com/symbol/AZN
Imfinzi (durvalumab) plus chemotherapy
ENHERTU® (fam-trastuzumab deruxtecan-nxki)
ENHERTU® (fam-trastuzumab deruxtecan-nxki)
Imfinzi plus chemotherapy granted Priority Review in the US for patients with locally advanced or metastatic biliary tract cancer based on TOPAZ-1 Phase III trial
PUBLISHED4 May 2022
4 May 2022 07:00 BST
First Phase III trial in this setting to show improved overall survival with an immunotherapy added to chemotherapy over standard-of-care chemotherapy alone
AstraZeneca’s supplemental Biologics License Application (sBLA) for Imfinzi (durvalumab), in combination with standard-of-care chemotherapy, has been accepted and granted Priority Review in the US for patients with locally advanced or metastatic biliary tract cancer (BTC).The Food and Drug Administration (FDA) grants Priority Review to applications for medicines that, if approved, would offer significant improvements over available options by demonstrating safety or efficacy improvements, preventing serious conditions, or enhancing patient compliance.1 The Prescription Drug User Fee Act date, the FDA action date for their regulatory decision, is during the third quarter of 2022.BTC is a group of rare and aggressive cancers that occur in the bile ducts and gallbladder. 2,3 Approximately 23,000 people in the US are diagnosed with BTC each year.2 These patients have a poor prognosis, with approximately 5% to 15% of patients with BTC surviving five years.4Susan Galbraith, Executive Vice President, Oncology R&D, AstraZeneca, said: “People with advanced biliary tract cancer have faced poor outcomes and limited treatment options for too long, and today’s news for the TOPAZ-1 trial underscores the urgency to deliver new, effective therapies in this setting. We are working closely with the FDA to bring the first immunotherapy-based option to patients with this devastating cancer and potentially set a new standard of care with Imfinzi plus chemotherapy.”The sBLA was based on results from an interim analysis of the TOPAZ-1 Phase III trial presented during the 2022 American Society of Clinical Oncology Gastrointestinal Cancers (ASCO GI) Symposium. The data showed Imfinzi plus chemotherapy (gemcitabine plus cisplatin) reduced the risk of death by 20% versus chemotherapy alone (based on a hazard ratio [HR] of 0.80; 95% confidence interval [CI], 0.66-0.97; 2-sided p=0.021). An estimated one in four (25%) patients treated with Imfinzi plus chemotherapy were alive at two years compared to one in 10 (10%) treated with chemotherapy alone.Results also showed a statistically significant 25% reduction in the risk of disease progression or death with Imfinzi plus chemotherapy (HR, 0.75; 95% CI, 0.64-0.89; 2-sided p=0.001). The Imfinzi combination was generally well tolerated and did not increase the discontinuation rate due to adverse events compared to chemotherapy alone.In December 2020, Imfinzi was granted Orphan Drug Designation in the US for the treatment of BTC.
TOPAZ-1
TOPAZ-1 is a randomised, double-blind, placebo controlled, multicentre, global Phase III trial of Imfinzi in combination with chemotherapy (gemcitabine plus cisplatin) versus placebo in combination with chemotherapy as a 1st-line treatment in 685 patients with unresectable advanced or metastatic BTC including intrahepatic and extrahepatic cholangiocarcinoma, and gallbladder cancer. Patients with ampullary carcinoma were excluded.The primary endpoint is overall survival and key secondary endpoints included progression-free survival, objective response rate and safety. The trial was conducted in 105 centres across 17 countries including in the US, Europe, South America and several countries in Asia including South Korea, Thailand, Japan and China.
Imfinzi
Imfinzi (durvalumab) is a human monoclonal antibody that binds to the PD-L1 protein and blocks the interaction of PD-L1 with the PD-1 and CD80 proteins, countering the tumour’s immune-evading tactics and releasing the inhibition of immune responses.Imfinzi is the only approved immunotherapy in the curative-intent setting of unresectable, Stage III non-small cell lung cancer (NSCLC) in patients whose disease has not progressed after chemoradiotherapy, and is the global standard of care in this setting based on the PACIFIC Phase III trial.Imfinzi is also approved in the US, EU, Japan, China and many other countries around the world for the treatment of extensive-stage small cell lung cancer (ES-SCLC) based on the CASPIAN Phase III trial. In 2021, updated results from the CASPIAN trial showed Imfinzi plus chemotherapy tripled patient survival at three years versus chemotherapy alone.Imfinzi is also approved for previously treated patients with advanced bladder cancer in several countries.Since the first approval in May 2017, more than 100,000 patients have been treated with Imfinzi.As part of a broad development programme, Imfinzi is being tested as a single treatment and in combinations with other anti-cancer treatments for patients with small cell lung cancer (SCLC), NSCLC, bladder cancer, several GI cancers, ovarian cancer, endometrial cancer, and other solid tumours.In the past year, Imfinzi combinations have demonstrated clinical benefit in multiple additional cancer settings with positive Phase III trials in unresectable advanced liver cancer (HIMALAYA) and metastatic NSCLC (POSEIDON). https://www.imfinzi.com/
Please visit astrazeneca.com and follow the Company on Twitter @AstraZeneca.
AstraZeneca's Imfinzi gets FDA priority review for biliary tract cancer
May 05, 2022 6:08 AM ET
By: Ravikash, SA News Editor
- The U.S. Food and Drug Administration granted priority review to AstraZeneca's (NASDAQ:AZN) Imfinzi, in combination with standard-of-care chemotherapy, to treat patients with locally advanced or metastatic biliary tract cancer (BCT).
- https://seekingalpha.com/news/3833069-astrazenecas-imfinzi-gets-fda-priority-review-for-biliary-tract-cancer
- https://seekingalpha.com/symbol/AZN
- https://www.astrazeneca.com
- https://www.imfinzi.com/
BIOTECNOVA™
KEYTRUDA® (pembrolizumab)
Tremelimumab in combination with Imfinzi (durvalumab)
ENHERTU® (fam-trastuzumab deruxtecan-nxki)
European Commission Approves Merck’s KEYTRUDA® (pembrolizumab) for Patients With Microsatellite Instability-High (MSI-H) or Deficient Mismatch Repair (dMMR) Tumors in Five Different Types of Cancer
April 29, 2022 6:45 am ET
KEYTRUDA is the First Immunotherapy to be Approved for Patients with MSI-H/dMMR Biomarkers in Five Different Types of Cancer in Europe
KENILWORTH, N.J.--(BUSINESS WIRE)-- Merck (NYSE: MRK), known as MSD outside the United States and Canada, today announced that the European Commission has approved KEYTRUDA, Merck’s anti-PD-1 therapy, as monotherapy for the treatment of microsatellite instability-high (MSI-H) or deficient mismatch repair (dMMR) tumors in adults with: unresectable or metastatic colorectal cancer after previous fluoropyrimidine-based combination therapy; advanced or recurrent endometrial carcinoma, who have disease progression on or following prior treatment with a platinum-containing therapy in any setting and who are not candidates for curative surgery or radiation; unresectable or metastatic gastric, small intestine or biliary cancer, who have disease progression on or following at least one prior therapy. This is the second approval for KEYTRUDA in Europe based on the MSI-H/dMMR biomarker. KEYTRUDA is also approved for the first-line treatment of metastatic MSI-H or dMMR colorectal cancer in adults.“Our company has a strong track record of applying precision medicine, through biomarkers like MSI-H and dMMR, to help identify patients most likely to respond to KEYTRUDA based on the genetic makeup of their individual cancer,” said Dr. Scot Ebbinghaus, vice president, global clinical development, Merck Research Laboratories. “For patients with MSI-H/dMMR colorectal cancer, KEYTRUDA monotherapy was approved in Europe as a first-line option in January 2021. Building on that approval, we are pleased that KEYTRUDA is now approved for the treatment of additional MSI-H/dMMR tumors, in certain second- or later-line patients with colorectal, endometrial, gastric, small intestine or biliary cancer.”“In the two studies supporting this approval, KEYTRUDA monotherapy showed strong objective response rates and durability of response in patients with five different types of MSI-H/dMMR cancers,” said Dr. Aurélien Marabelle, Immuno-Oncologist at Gustave Roussy Cancer Center and Professor of Clinical Immunology at the University of Paris Saclay. “The EU approval of KEYTRUDA is an important milestone for patients living with these MSI-H/dMMR cancers who have had few treatment options and face worse outcomes when diagnosed at an advanced stage.”This approval allows marketing of KEYTRUDA monotherapy in all 27 European Union (EU) member states plus Iceland, Lichtenstein, Norway and Northern Ireland.
Data Supporting the European Approval
The approval was based on data from KEYNOTE-164 (NCT02460198) and KEYNOTE-158 (NCT02628067), multicenter, non-randomized, open-label Phase 2 trials evaluating KEYTRUDA in patients with advanced MSI-H or dMMR solid tumors. The KEYNOTE-164 trial enrolled 124 patients with unresectable or metastatic MSI-H or dMMR colorectal cancer that progressed following prior fluoropyrimidine-based therapy in combination with irinotecan and/or oxaliplatin. The KEYNOTE-158 trial enrolled 355 patients with unresectable or metastatic MSI-H or dMMR solid tumors, including endometrial, gastric, small intestine or biliary cancer. Microsatellite instability or MMR tumor status was determined by prospectively using polymerase chain reaction or immunohistochemistry, respectively. Patients received KEYTRUDA 200 mg administered intravenously every three weeks until unacceptable toxicity or disease progression. Clinically stable patients with initial evidence of disease progression were permitted to remain on treatment until disease progression was confirmed. Patients without disease progression were treated for up to 24 months (up to 35 cycles). The primary efficacy outcome measure for the trials was objective response rate (ORR) as assessed by blinded independent central review using RECIST v1.1. The secondary efficacy outcome measures for the trials included duration of response (DOR), progression-free survival and overall survival.Efficacy results from the KEYNOTE-164 and KEYNOTE-158 trials are summarized below. For patients with:
- Colorectal cancer (n=124), the ORR was 34% (95% CI, 25.6-42.9), including a complete response (CR) rate of 10% and a partial response (PR) rate of 24%, at a median follow-up time of 37.3 months (range, 0.1 to 65.2). Median DOR was not reached (range, 4.4 to 58.5+ months), and of responding patients, 92% had responses lasting at least three years.
- Endometrial cancer (n=83), the ORR was 51% (95% CI, 39.4-61.8), including a CR rate of 16% and a PR rate of 35%, at a median follow-up time of 21.9 months (range, 1.5 to 64.0). Median DOR was not reached (range, 2.9 to 60.4+ months), and of responding patients, 85% had responses lasting at least one year, and 60% had responses lasting at least three years.
- Gastric cancer (n=51), the ORR was 37% (95% CI, 24.1-51.9), including a CR rate of 14% and a PR rate of 24%, at a median follow-up time of 13.9 months (range, 1.1 to 66.9). Median DOR was not reached (range, 6.2 to 63.0+ months), and of responding patients, 90% had responses lasting at least one year, and 81% had responses lasting at least three years.
- Small intestine cancer (n=27), the ORR was 56% (95% CI, 35.3-74.5), including a CR rate of 15% and a PR rate of 41%, at a median follow-up time of 29.1 months (range, 4.2 to 67.7). Median DOR was not reached (range, 3.7+ to 57.3+ months), and of responding patients, 93% had responses lasting at least one year, and 73% had responses lasting at least three years.
- Biliary cancer (n=22), the ORR was 41% (95% CI, 20.7-63.6), including a CR rate of 14% and a PR rate of 27%, at a median follow-up time of 19.4 months (range, 1.1 to 60.8). Median DOR was 30.6 months (range, 6.2 to 46.0+), and of responding patients, 89% had responses lasting at least one year, and 42% had responses lasting at least three years.
The safety of KEYTRUDA as monotherapy has been evaluated in 7,148 patients with advanced melanoma, resected stage III melanoma (adjuvant therapy), non-small cell lung cancer, classical Hodgkin lymphoma, urothelial carcinoma, head and neck squamous cell carcinoma, colorectal cancer, endometrial, gastric, small intestine, biliary, pancreatic cancer or adjuvant therapy of renal cell carcinoma across four doses (2 mg/kg bodyweight [bw] every three weeks, 200 mg every three weeks or 10 mg/kg bw every two or three weeks) in clinical studies. In this patient population, the most frequent adverse reactions with KEYTRUDA were fatigue (31%), diarrhea (22%) and nausea (21%). The majority of adverse reactions reported for KEYTRUDA monotherapy were of Grades 1 or 2 severity. The most serious adverse reactions were immune-related adverse reactions and severe infusion-related reactions. The incidences of immune-related adverse reactions were 36.1% for all Grades and 8.9% for Grades 3-5 for KEYTRUDA monotherapy in the adjuvant setting (n=1,480) and 24.2% for all Grades and 6.4% for Grades 3-5 for KEYTRUDA monotherapy in the metastatic setting (n=5,375). No new immune-related adverse reactions were identified in the adjuvant setting.
About Microsatellite Instability-High (MSI-H) and Deficient Mismatch Repair (dMMR)
Microsatellite instability (MSI) and deficient mismatch repair (dMMR) are biomarkers that have been identified in many different types of cancer and that can be hereditary or random. MSI is a change that occurs in the DNA of certain cells, such as cancer cells, in which the number of repeated DNA bases in a microsatellite (which is a short, repeated sequence of DNA) is different from what it was when the microsatellite was inherited. dMMR describes cells that have mutations in certain genes involved in correcting mistakes made when DNA is copied into a cell when dividing. High levels of MSI (MSI-H) and dMMR can occur when a cell is unable to repair mistakes during that division process.
About KEYTRUDA® (pembrolizumab) Injection, 100 mg
KEYTRUDA is an anti-programmed death receptor-1 (PD-1) therapy that works by increasing the ability of the body’s immune system to help detect and fight tumor cells. KEYTRUDA is a humanized monoclonal antibody that blocks the interaction between PD-1 and its ligands, PD-L1 and PD-L2, thereby activating T lymphocytes which may affect both tumor cells and healthy cells.Merck has the industry’s largest immuno-oncology clinical research program. There are currently more than 1,700 trials studying KEYTRUDA across a wide variety of cancers and treatment settings. The KEYTRUDA clinical program seeks to understand the role of KEYTRUDA across cancers and the factors that may predict a patient's likelihood of benefitting from treatment with KEYTRUDA, including exploring several different biomarkers.
Selected KEYTRUDA® (pembrolizumab) Indications in the U.S.
MelanomaKEYTRUDA is indicated for the treatment of patients with unresectable or metastatic melanoma.KEYTRUDA is indicated for the adjuvant treatment of adult and pediatric (12 years and older) patients with stage IIB, IIC, or III melanoma following complete resection.Non-Small Cell Lung CancerKEYTRUDA, in combination with pemetrexed and platinum chemotherapy, is indicated for the first-line treatment of patients with metastatic nonsquamous non-small cell lung cancer (NSCLC), with no EGFR or ALK genomic tumor aberrations.KEYTRUDA, in combination with carboplatin and either paclitaxel or paclitaxel protein-bound, is indicated for the first-line treatment of patients with metastatic squamous NSCLC.KEYTRUDA, as a single agent, is indicated for the first-line treatment of patients with NSCLC expressing PD-L1 [tumor proportion score (TPS) ≥1%] as determined by an FDA-approved test, with no EGFR or ALK genomic tumor aberrations, and is:
- stage III where patients are not candidates for surgical resection or definitive chemoradiation, or
- metastatic.
KEYTRUDA, as a single agent, is indicated for the treatment of patients with metastatic NSCLC whose tumors express PD-L1 (TPS ≥1%) as determined by an FDA-approved test, with disease progression on or after platinum-containing chemotherapy. Patients with EGFR or ALK genomic tumor aberrations should have disease progression on FDA-approved therapy for these aberrations prior to receiving KEYTRUDA.Head and Neck Squamous Cell CancerKEYTRUDA, in combination with platinum and fluorouracil (FU), is indicated for the first-line treatment of patients with metastatic or with unresectable, recurrent head and neck squamous cell carcinoma (HNSCC).KEYTRUDA, as a single agent, is indicated for the first-line treatment of patients with metastatic or with unresectable, recurrent HNSCC whose tumors express PD-L1 [Combined Positive Score (CPS) ≥1] as determined by an FDA-approved test.KEYTRUDA, as a single agent, is indicated for the treatment of patients with recurrent or metastatic HNSCC with disease progression on or after platinum-containing chemotherapy.Classical Hodgkin LymphomaKEYTRUDA is indicated for the treatment of adult patients with relapsed or refractory classical Hodgkin lymphoma (cHL).KEYTRUDA is indicated for the treatment of pediatric patients with refractory cHL, or cHL that has relapsed after 2 or more lines of therapy.Primary Mediastinal Large B-Cell LymphomaKEYTRUDA is indicated for the treatment of adult and pediatric patients with refractory primary mediastinal large B-cell lymphoma (PMBCL), or who have relapsed after 2 or more prior lines of therapy.KEYTRUDA is not recommended for treatment of patients with PMBCL who require urgent cytoreductive therapy.Urothelial CarcinomaKEYTRUDA is indicated for the treatment of patients with locally advanced or metastatic urothelial carcinoma (mUC):
- who are not eligible for any platinum-containing chemotherapy, or
- who have disease progression during or following platinum-containing chemotherapy or within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy.
Non-muscle Invasive Bladder CancerKEYTRUDA is indicated for the treatment of patients with Bacillus Calmette-Guerin-unresponsive, high-risk, non-muscle invasive bladder cancer (NMIBC) with carcinoma in situ with or without papillary tumors who are ineligible for or have elected not to undergo cystectomy.Microsatellite Instability-High or Mismatch Repair Deficient CancerKEYTRUDA is indicated for the treatment of adult and pediatric patients with unresectable or metastatic microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) solid tumors that have progressed following prior treatment and who have no satisfactory alternative treatment options.This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials. The safety and effectiveness of KEYTRUDA in pediatric patients with MSI-H central nervous system cancers have not been established.Microsatellite Instability-High or Mismatch Repair Deficient Colorectal CancerKEYTRUDA is indicated for the treatment of patients with unresectable or metastatic MSI-H or dMMR colorectal cancer (CRC).Gastric CancerKEYTRUDA, in combination with trastuzumab, fluoropyrimidine- and platinum-containing chemotherapy, is indicated for the first-line treatment of patients with locally advanced unresectable or metastatic HER2-positive gastric or gastroesophageal junction (GEJ) adenocarcinoma.This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.Esophageal CancerKEYTRUDA is indicated for the treatment of patients with locally advanced or metastatic esophageal or gastroesophageal junction (GEJ) (tumors with epicenter 1 to 5 centimeters above the GEJ) carcinoma that is not amenable to surgical resection or definitive chemoradiation either:
- in combination with platinum- and fluoropyrimidine-based chemotherapy, or
- as a single agent after one or more prior lines of systemic therapy for patients with tumors of squamous cell histology that express PD-L1 (CPS ≥10) as determined by an FDA-approved test.
Cervical CancerKEYTRUDA, in combination with chemotherapy, with or without bevacizumab, is indicated for the treatment of patients with persistent, recurrent, or metastatic cervical cancer whose tumors express PD-L1 (CPS ≥1) as determined by an FDA-approved test.KEYTRUDA, as a single agent, is indicated for the treatment of patients with recurrent or metastatic cervical cancer with disease progression on or after chemotherapy whose tumors express PD-L1 (CPS ≥1) as determined by an FDA-approved test.Hepatocellular CarcinomaKEYTRUDA is indicated for the treatment of patients with hepatocellular carcinoma (HCC) who have been previously treated with sorafenib. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.Merkel Cell CarcinomaKEYTRUDA is indicated for the treatment of adult and pediatric patients with recurrent locally advanced or metastatic Merkel cell carcinoma (MCC). This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.Renal Cell CarcinomaKEYTRUDA, in combination with axitinib, is indicated for the first-line treatment of adult patients with advanced renal cell carcinoma (RCC).KEYTRUDA is indicated for the adjuvant treatment of patients with RCC at intermediate-high or high risk of recurrence following nephrectomy, or following nephrectomy and resection of metastatic lesions.Endometrial CarcinomaKEYTRUDA, as a single agent, is indicated for the treatment of patients with advanced endometrial carcinoma that is MSI-H or dMMR, as determined by an FDA-approved test, who have disease progression following prior systemic therapy in any setting and are not candidates for curative surgery or radiation.Tumor Mutational Burden-High CancerKEYTRUDA is indicated for the treatment of adult and pediatric patients with unresectable or metastatic tumor mutational burden-high (TMB-H) [≥10 mutations/megabase] solid tumors, as determined by an FDA-approved test, that have progressed following prior treatment and who have no satisfactory alternative treatment options. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials. The safety and effectiveness of KEYTRUDA in pediatric patients with TMB-H central nervous system cancers have not been established.Cutaneous Squamous Cell CarcinomaKEYTRUDA is indicated for the treatment of patients with recurrent or metastatic cutaneous squamous cell carcinoma (cSCC) or locally advanced cSCC that is not curable by surgery or radiation.Triple-Negative Breast CancerKEYTRUDA is indicated for the treatment of patients with high-risk early-stage triple-negative breast cancer (TNBC) in combination with chemotherapy as neoadjuvant treatment, and then continued as a single agent as adjuvant treatment after surgery.KEYTRUDA, in combination with chemotherapy, is indicated for the treatment of patients with locally recurrent unresectable or metastatic TNBC whose tumors express PD-L1 (CPS ≥10) as determined by an FDA-approved test.https://www.keytruda.com/ For more information, visit www.merck.com and connect with us on Twitter, Facebook, Instagram, YouTube and LinkedIn.
Please see Prescribing Information for KEYTRUDA (pembrolizumab) at http://www.merck.com/product/usa/pi_circulars/k/keytruda/keytruda_pi.pdf and Medication Guide for KEYTRUDA at http://www.merck.com/product/usa/pi_circulars/k/keytruda/keytruda_mg.pdf .
Source: Merck & Co., Inc.
Merck wins European approval to market Keytruda for more cancer indications
Apr. 29, 2022 7:09 AM ET
By: Dulan Lokuwithana, SA News Editor
- Merck (NYSE:MRK) announced on Friday that the European Commission approved its anti-PD-1 therapy, Keytruda for a few more indications in cancer.
- https://seekingalpha.com/news/3829276-merck-wins-european-approval-to-market-keytruda-for-more-cancer-indications
- https://seekingalpha.com/symbol/MRK
- https://www.keytruda.com/
- https://www.merck.com/
ENHERTU® (fam-trastuzumab deruxtecan-nxki)
Tremelimumab in combination with Imfinzi (durvalumab)
ENHERTU® (fam-trastuzumab deruxtecan-nxki)
Enhertu granted Breakthrough Therapy Designation in the US for patients with HER2-low metastatic breast cancer
PUBLISHED27 April 2022
27 April 2022 07:00 BST
Based on DESTINY-Breast04 results where AstraZeneca and Daiichi Sankyo’s Enhertu demonstrated a significant improvement in both progression-free survival and overall survival Enhertu has now been granted five Breakthrough Therapy Designations, including three in breast cancer and one in both lung and gastric cancers
AstraZeneca and Daiichi Sankyo’s Enhertu (trastuzumab deruxtecan) has been granted Breakthrough Therapy Designation (BTD) in the US for the treatment of adult patients with unresectable or metastatic HER2-low (IHC 1+ or IHC 2+/ISH-negative) breast cancer who have received a prior systemic therapy in the metastatic setting or developed disease recurrence during or within six months of completing adjuvant chemotherapy. Patients with hormone receptor (HR) positive breast cancer should additionally have received or be ineligible for endocrine therapy.Enhertu is a specifically engineered HER2-directed antibody drug conjugate (ADC) being jointly developed and commercialised by AstraZeneca and Daiichi Sankyo.The Food and Drug Administration’s (FDA) BTD is designed to accelerate the development and regulatory review of potential new medicines that are intended to treat a serious condition and address a significant unmet medical need. The new medicine needs to have shown encouraging preliminary clinical results that demonstrate substantial improvement on a clinically significant endpoint over available medicines.Up to half of all patients with breast cancer have tumours with a HER2 immunohistochemistry (IHC) score of 1+, or 2+ in combination with a negative in-situ hybridisation (ISH) test, a level of HER2 expression not currently eligible for HER2-targeted therapy.1-4 Low HER2 expression occurs in both HR-positive and HR-negative disease.5HER2 testing is routinely used to determine appropriate treatment options for patients with metastatic breast cancer. Targeting the lower range of expression in the HER2 spectrum may offer another approach to delay disease progression and extend survival in patients with metastatic breast cancer.6 Currently chemotherapy remains the only treatment option for patients with HR-positive tumours following progression on endocrine (hormone) therapy.7 Few targeted options are available for those who are HR-negative.8Susan Galbraith, Executive Vice President, Oncology R&D, AstraZeneca said: “Today’s news is a significant validation of the potential we see for the historic DESTINY-Breast04 trial to enable a paradigm shift in how breast cancer is classified by targeting the full spectrum of HER2 expression. Enhertu continues to show transformative potential, and this milestone represents an important advance for patients with HER2-low metastatic breast cancer who are in urgent need of new treatment options and better outcomes.”Ken Takeshita, Global Head, R&D, Daiichi Sankyo said: “Historically, only patients with HER2-positive metastatic breast cancer were shown to benefit from HER2-directed therapy. DESTINY-Breast04, in which Enhertu showed a clinically meaningful survival benefit in patients with HER2-low metastatic breast cancer, is the first trial to demonstrate that selecting patients for treatment based on low expression of HER2 has the potential to change the diagnostic and treatment paradigms for these patients. This Breakthrough Therapy Designation acknowledges the potential of Enhertu to fulfil an unmet medical need and we look forward to working closely with the FDA to bring the first HER2-directed therapy to patients with metastatic breast cancer whose tumours have lower levels of HER2 expression.”The FDA granted the BTD based on data from the pivotal DESTINY-Breast04 Phase III trial which reported positive high-level results in February 2022. In the trial, Enhertu demonstrated a statistically significant and clinically meaningful improvement in both progression-free survival (PFS) and overall survival (OS) in patients with HER2-low unresectable and/or metastatic breast cancer in all randomised patients with HR-positive and HR-negative disease versus physician’s choice of chemotherapy, which is the current standard of care. The safety profile of Enhertu was consistent with previous clinical trials with no new safety concerns identified. The data will be presented at an upcoming medical meeting.This is the third BTD for Enhertu in breast cancer. Enhertu previously received BTD’s for the treatment of second-line HER2-positive metastatic breast cancer in 2021 and later-line HER2-positive metastatic breast cancer in 2017. Two additional BTD’s for Enhertu were granted in 2020 for HER2-mutant metastatic non-small cell lung cancer (NSCLC) and HER2-positive metastatic gastric cancer.
DESTINY-Breast04
DESTINY-Breast04 is a global, randomised, open-label, registrational Phase III trial evaluating the efficacy and safety of Enhertu (5.4mg/kg) versus physician’s choice of chemotherapy (capecitabine, eribulin, gemcitabine, paclitaxel or nab-paclitaxel) in patients with HR-positive (n=480) or HR-negative (n=60) HER2-low unresectable and/or metastatic breast cancer previously treated with one or two prior lines of chemotherapy. Patients were randomised 2:1 to receive either Enhertu or chemotherapy.The primary endpoint of DESTINY-Breast04 is PFS in patients with HR-positive disease based on blinded independent central review (BICR). Key secondary endpoints include PFS based on BICR in all randomised patients (HR-positive and HR-negative disease), OS in patients with HR-positive disease and OS in all randomised patients (HR-positive and HR-negative disease). Other secondary endpoints include PFS based on BICR and investigator assessment, duration of response based on BICR and safety.DESTINY-Breast04 enrolled approximately 540 patients at multiple sites in Asia, Europe and North America. For more information about the trial, visit ClinicalTrials.gov.
Enhertu
Enhertu is a HER2-directed ADC. Designed using Daiichi Sankyo’s proprietary DXd ADC technology, Enhertu is the lead ADC in the oncology portfolio of Daiichi Sankyo and the most advanced programme in AstraZeneca’s ADC scientific platform. Enhertu consists of a HER2 monoclonal antibody attached to a topoisomerase I inhibitor payload, an exatecan derivative, via a stable tetrapeptide-based cleavable linker.Enhertu (5.4mg/kg) is approved in more than 40 countries for the treatment of adult patients with unresectable or metastatic HER2-positive breast cancer who have received two or more prior anti-HER2-based regimens based on the results from the DESTINY-Breast01 trial.Enhertu (6.4mg/kg) is approved in several countries for the treatment of adult patients with locally advanced or metastatic HER2-positive gastric or gastroesophageal junction (GEJ) adenocarcinoma who have received a prior trastuzumab-based regimen based on the results from the DESTINY-Gastric01 trial.https://www.enhertu.com/en/
Daiichi Sankyo collaboration
Daiichi Sankyo Company, Limited (TSE: 4568) [referred to as Daiichi Sankyo] and AstraZeneca entered into a global collaboration to jointly develop and commercialise Enhertu (a HER2-directed ADC) in March 2019, and datopotamab deruxtecan (DS-1062; a TROP2-directed ADC) in July 2020, except in Japan where Daiichi Sankyo maintains exclusive rights. Daiichi Sankyo is responsible for manufacturing and supply of Enhertu and datopotamab deruxtecan.
Please visit astrazeneca.com and follow the Company on Twitter @AstraZeneca.
AstraZeneca, Daiichi Sankyo's Enhertu gets FDA breakthrough therapy tag for breast cancer subtype
Apr. 27, 2022 6:20 AM ET
Daiichi Sankyo Company, Limited (DSNKY), AZN DSKYF
By: Ravikash, SA News Editor1 Comment
- The Food and Drug Administration (FDA) granted breakthrough therapy designation to AstraZeneca (NASDAQ:AZN) and Daiichi Sankyo's (OTCPK:DSKYF) (OTCPK:DSNKY) Enhertu to treat certain patients with breast cancer.
- https://seekingalpha.com/news/3827402-astrazeneca-daiichi-sankyos-enhertu-gets-fda-breakthrough-therapy-tag-for-breast-cancer-subtype
- https://seekingalpha.com/symbol/DSKYF
- https://seekingalpha.com/symbol/DSNKY
- https://seekingalpha.com/symbol/AZN
- https://www.enhertu.com/en/
- https://www.astrazeneca.com/
Tremelimumab in combination with Imfinzi (durvalumab)
Tremelimumab in combination with Imfinzi (durvalumab)
Tremelimumab in combination with Imfinzi (durvalumab)
Tremelimumab accepted under Priority Review in the US for patients with unresectable liver cancer in combination with Imfinzi
PUBLISHED25 April 2022
25 April 2022 07:00 BST
STRIDE regimen of a single priming dose of tremelimumab added to Imfinzi is the first dual immune checkpoint blockade regimen to improve overall survival in a Phase III trial in this setting
AstraZeneca’s Biologics License Application (BLA) for tremelimumab has been accepted for Priority Review in the US, supporting the indication of a single priming dose of the anti-CTLA4 antibody added to Imfinzi (durvalumab) for the treatment of patients with unresectable hepatocellular carcinoma (HCC). A supplemental BLA (sBLA) has also been submitted for Imfinzi in this indication. This novel dose and schedule of the combination is called the STRIDE regimen (Single Tremelimumab Regular Interval Durvalumab).
The Prescription Drug User Fee Act date, the Food and Drug Administration (FDA) action date for their regulatory decision, is during the fourth quarter of 2022 following the use of a priority review voucher.
Liver cancer, of which HCC is the most common type, is the third-leading cause of cancer death and the sixth most commonly diagnosed cancer worldwide.1,2 Approximately 26,000 people in the US present with advanced, unresectable HCC each year.3
Susan Galbraith, Executive Vice President, Oncology R&D, AstraZeneca, said: “The HIMALAYA Phase III trial showed an unprecedented three-year overall survival in this setting with a single priming dose of tremelimumab added to Imfinzi, highlighting the potential for this regimen to improve longer-term survival outcomes. Patients with advanced liver cancer are in great need of new treatment options, and we are working closely with the FDA to bring this novel approach to patients in the US as soon as possible.”
The BLA for tremelimumab and sBLA for Imfinzi are based on final results from the HIMALAYA Phase III trial presented at the 2022 American Society of Clinical Oncology Gastrointestinal Cancers Symposium.
In this trial, patients treated with the STRIDE regimen experienced a 22% reduction in the risk of death versus sorafenib (based on a hazard ratio [HR] of 0.78, 96.02% confidence interval [CI] 0.65-0.93; p=0.0035).4 Nearly one in three (31%) patients were still alive at three years versus one in five (20%) for sorafenib.4
The safety profiles of the STRIDE regimen and for Imfinzi alone were consistent with the known profiles of each medicine, and no new safety signals were identified.
Imfinzi and tremelimumab were granted Orphan Drug Designation in the US for the treatment of HCC in January 2020.
As part of its extensive clinical development programme in gastrointestinal (GI) cancers, AstraZeneca is further assessing Imfinzi across multiple liver cancer settings, including locoregional HCC (EMERALD-1, EMERALD-3) and adjuvant HCC (EMERALD-2).
HIMALAYA
HIMALAYA was a randomised, open-label, multicentre, global Phase III trial of Imfinzi monotherapy and the STRIDE regimen, comprising a single priming dose of tremelimumab 300mg added to Imfinzi 1500mg followed by Imfinzi every four weeks versus sorafenib, a standard-of-care multi-kinase inhibitor.
The trial included a total of 1,324 patients with unresectable, advanced HCC who had not been treated with prior systemic therapy and were not eligible for locoregional therapy (treatment localised to the liver and surrounding tissue).
The trial was conducted in 181 centres across 16 countries, including in the US, Canada, Europe, South America and Asia. The primary endpoint is overall survival (OS) for STRIDE versus sorafenib and key secondary endpoints included OS for Imfinzi versus sorafenib, objective response rate and progression-free survival (PFS) for STRIDE and for Imfinzi alone.
Imfinzi
Imfinzi (durvalumab) is a human monoclonal antibody that binds to the PD-L1 protein and blocks the interaction of PD-L1 with the PD-1 and CD80 proteins, countering the tumour’s immune-evading tactics and releasing the inhibition of immune responses.
Imfinzi is the only approved immunotherapy in the curative-intent setting of unresectable, Stage III non-small cell lung cancer (NSCLC) in patients whose disease has not progressed after chemoradiotherapy, and is the global standard of care in this setting based on the PACIFIC Phase III trial.
Imfinzi is also approved in the US, EU, Japan, China and many other countries around the world for the treatment of extensive-stage small cell lung cancer (ES-SCLC) based on the CASPIAN Phase III trial. In 2021, updated results from the CASPIAN trial showed Imfinzi plus chemotherapy tripled patient survival at three years versus chemotherapy alone.
In the past year, Imfinzi has demonstrated clinical benefit in multiple additional cancer settings with positive Phase III trials in advanced biliary tract cancer (TOPAZ-1), unresectable advanced liver cancer (HIMALAYA) and metastatic NSCLC (POSEIDON).
As part of a broad development programme, Imfinzi is being tested as a single treatment and in combinations with other anti-cancer treatments for patients with small cell lung cancer, NSCLC, bladder cancer, several gastrointestinal cancers, ovarian cancer, endometrial cancer, and other solid tumours.
Tremelimumab
Tremelimumab is a human monoclonal antibody and potential new medicine that targets the activity of cytotoxic T-lymphocyte-associated protein 4 (CTLA-4). Tremelimumab blocks the activity of CTLA-4, contributing to T-cell activation, priming the immune response to cancer and fostering cancer cell death.
Beyond HIMALAYA, tremelimumab is being tested in combination with Imfinzi across multiple tumour types including locoregional HCC (EMERALD-3), SCLC (ADRIATIC) and bladder cancer (VOLGA and NILE).
Tremelimumab is also under review by global regulatory authorities in combination with Imfinzi and chemotherapy in 1st-line metastatic NSCLC based on the results of the POSEIDON Phase III trial, which showed the addition of a short course of tremelimumab to Imfinzi plus chemotherapy improved both overall and progression-free survival compared to chemotherapy alone.
Please visit astrazeneca.com and follow the Company on Twitter @AstraZeneca.
AstraZeneca gets FDA priority review for new dosing regimen of tremelimumab/Imfinzi in liver cancer
Apr. 25, 2022 5:42 AM ET
AstraZeneca PLC (AZN) BAYZF, BAYRY
By: Ravikash, SA News Editor1 Comment
The Food and Drug Administration (FDA) granted priority review to AstraZeneca's (NASDAQ:AZN) application for a single priming dose of tremelimumab added to Imfinzi (durvalumab) to treat patients with unresectable hepatocellular carcinoma, a type of liver cancer.
https://seekingalpha.com/symbol/AZN
Veklury® (Remdesivir)
ENHERTU® (fam-trastuzumab deruxtecan-nxki)
Tremelimumab in combination with Imfinzi (durvalumab)
April 24, 2022
Several New Studies Presented at ECCMIC 2022 Confirm Veklury® (Remdesivir) Activity in Treating COVID-19
-- Real-World Evidence from More than 850,000 Hospitalized Patients Provides Clinical Insights on the Use of Veklury (Remdesivir) as Stand of Care COVID-19 Treatment ---- New Post-hoc Analysis of Non-Hospitalized COVID-19 Patients in the Phase 3 PINETREE Study Demonstrates Veklury Treatment Initiated Within 5 Days of Symptoms Reduced Risk for Hospitalization by 90% --FOSTER CITY, Calif.--(BUSINESS WIRE)-- Gilead Sciences, Inc. (Nasdaq: GILD) today announced findings from two studies, which provide further insights on the use of Veklury® (remdesivir) for the treatment of hospitalized and non-hospitalized patients with COVID-19. The first study is a retrospective observational analysis of the real-world treatment data from the Premier Healthcare Database consisting of 853,219 patients hospitalized with COVID-19 across the United States. This analysis found that more than 50% of hospitalized COVID-19 patients received Veklury, predominantly in combination with other therapies. An oral presentation of this real-world data analysis will be given on April 25 at 11 a.m. Western European Summer Time in Hall P at the European Congress of Clinical Microbiology & Infectious Diseases (ECCMID 2022). A separate study, which is a new post-hoc analysis of data from the Phase 3 PINETREE study, demonstrated that use of Veklury within five days of symptom onset or between 5 to 7 days of symptom onset reduced hospitalizations in patients at high risk for severe COVID-19 disease. This post-hoc analysis was presented as a poster (#L0447) at ECCMID.The observational analysis of real-world data also found that as the pandemic progressed, initiation of Veklury within two days of hospitalization increased from 41% to 91% between May 2020 and December 2021. During this period, as new variants arose and disease severity fluctuated, median hospital length of stay (LOS) decreased from seven to six days with the greatest benefit in invasive mechanical ventilation/ ECMO patients (15 to 11 days). While ICU use decreased from 34% to 27%, with the greatest benefit in high-flow oxygen/non-invasive ventilation (66% to 52%), overall ICU LOS remained the same. Overall mortality rates remained stable at 16%, with the greatest decline over time in patients on low-flow supplemental oxygen (15% to 12%). These results confirm Veklury’s position as a foundational treatment for hospitalized patients with COVID-19 and signify the need to treat patients early before they become more severely ill with COVID-19.“In a pandemic, real world analysis has a particularly important role in helping us understand how treatment choices are evolving over time as we work to discover the most effective treatment options for patients. We've long understood that antivirals work optimally for respiratory viruses when they are given as early as possible, without delay. This data confirms that antiviral treatment is now initiated sooner in hospitalizations and that throughout the pandemic, remdesivir has remained the foundation for hospitalized patients with COVID-19,” said Robert L. Gottlieb, MD, PhD, Baylor University Medical Center and Baylor Scott & White Research Institute. “Additionally, as healthcare providers' experience and confidence in COVID-19 therapeutic options has increased, so too has the use of therapeutic combinations, reflecting the incremental incorporation of evidence-based therapies.”The new post-hoc analysis from a Phase 3 double-blind, placebo-controlled trial (PINETREE) demonstrating that a three-day course of Veklury treatment significantly reduced the risk of hospitalization was also presented at ECCMID. The analysis assessed the variability of treatment effect with Veklury by time of symptom onset and number of baseline risk factors. The study concluded that Veklury reduced hospitalizations in patients at high risk for severe COVID-19 disease when initiated anytime within a 7-day window from symptom onset. As expected with antiviral therapy, the benefit was modestly greater the sooner Veklury was administered. Patients treated with Veklury within five days of symptom onset had a 90% reduced risk for hospitalization. Additionally, patients who received Veklury after five 5 days of symptom onset experienced an 81% reduction in risk of hospitalization. This new analysis builds on the previously presented primary endpoint analysis, in which Veklury demonstrated a statistically significant 87% reduction in risk for the composite primary endpoint of COVID-19 related hospitalization or all-cause death by Day 28 (0.7% [2/279]) compared with placebo (5.3% [15/283]) p=0.008); no deaths occurred in either arm of the study through the primary endpoint.“The data presented at ECCMID, not only underscore Veklury as the antiviral standard of care for COVID-19 treatment in hospitalized patients, but they also further emphasize that patients can benefit from Veklury when it’s given up to seven days after the onset of symptoms and that the benefit is greater the sooner it is administered,” said Frank Duff, Senior Vice President, Virology Therapeutic Head, Gilead Sciences. “As the pandemic has progressed and the utility of other treatments against new variants has shifted, we are proud that Veklury has remained the foundation for patients hospitalized with COVID-19.”Gilead presented two additional studies from the company’s COVID-19 clinical and real-world evidence programs at the conference.
- Data from the CARAVAN study evaluated safety, pharmacokinetic, virologic, and clinical outcomes of Veklury treatment in pediatric patients who were 28 days of age and older. The interim analysis of Veklury in pediatric patients hospitalized with COVID-19 with ages ranging from 28 days to less than 18 years demonstrated that Veklury was generally well tolerated, with a high proportion of participants showing clinical improvement and recovery. Overall, no new safety findings for Veklury were noted. In the study, 75% and 85% showed clinical improvement (≥2 point increase on the ordinal scale) at Day 10 and last assessment, respectively, while 60% and 83% were discharged by Day 10 and Day 30, respectively. Overall, 38 patients (72%) experienced AEs, with 11 patients (21%) experiencing serious adverse events (SAEs) that were determined not to be study-drug related, including 3 participant deaths which were consistent with the patients’ underlying medical condition prior to study entry or with COVID-19 disease during hospitalization.
- A real-world evidence analysis evaluated data from 2,310 patients hospitalized with COVID-19 who had previously undergone kidney transplantation. The analysis found that in this patient population, overall mortality was comparable to the general population hospitalized with COVID-19, but markedly increased for those with diminished renal function, comorbidities, and higher oxygen requirements upon admission. Insights from this study help inform clinical decision-making in the context of management of kidney transplant patients and other solid-organ transplant recipients, alike.
About Veklury
Veklury (remdesivir) is a nucleotide analog invented by Gilead, building on more than a decade of the company’s antiviral research. Veklury is a foundation for the treatment of hospitalized patients with COVID-19 and is a recommended treatment for reducing disease progression in non-hospitalized patients at high risk of disease progression. Veklury has an established safety profile and minimal drug interactions in diverse populations. At this time, more than half of patients hospitalized with COVID-19 in the United States are treated with Veklury. It can help reduce disease progression across a spectrum of disease severity and enable patients to recover faster, freeing up limited hospital resources and saving healthcare systems money.Veklury was approved by the FDA in October 2020, for adults and pediatric patients 12 years of age and older and weighing at least 40 kg for the treatment of COVID-19 requiring hospitalization. In January 2022, the FDA approved a supplemental NDA to expand the indication to non-hospitalized adult and adolescent patients who are at high risk of progression to severe COVID-19, including hospitalization or death. This allows for Veklury to be administered in qualified outpatient settings that can administer daily intravenous (IV) infusions over three consecutive days. Veklury also has an Emergency Use Authorization (EUA) for non-hospitalized pediatric patients weighing at least 3.5 kg who are younger than 12 years of age or weighing less than 40 kg who are at high risk of disease progression, in addition to those with COVID-19 requiring hospitalization. Veklury is contraindicated in patients who are allergic to Veklury or any of its components; please see below for additional Important Safety Information for Veklury.Veklury continues to demonstrate durable activity against SARS-CoV2 as it evolves. Veklury is a nucleotide analog that directly inhibits viral replication inside of the cell by targeting the SARS-CoV-2 viral RNA polymerase. In vitro laboratory testing in multiple independent studies shows that Veklury continues to demonstrate durable activity against SARS-CoV2 as it evolves, including the Omicron variant and its subvariants BA.1 and BA.2. As new SARS-CoV-2 variants of concern emerge around the world, Gilead continuously evaluates the effectiveness of Veklury against viral variants.Veklury is approved or authorized for temporary use in approximately 50 countries worldwide. To date, Veklury and generic remdesivir have been made available to more than 11 million patients around the world, including more than 7 million people in 127 middle- and low-income countries through Gilead’s voluntary licensing program. These licenses currently remain royalty-free, reflecting Gilead’s existing commitment to enabling broad patient access to remdesivir.
U.S. Indication for Veklury
Veklury® (remdesivir 100 mg for injection) is indicated for the treatment of COVID-19 in adults and pediatric patients (12 years of age and older and weighing at least 40 kg) with positive results of direct SARS-CoV-2 viral testing, who are:
- Hospitalized, or
- Not hospitalized and have mild-to-moderate COVID-19 and are at high risk for progression to severe COVID-19, including hospitalization or death.
Veklury should only be administered in settings in which health care providers have immediate access to medications to treat a severe infusion or hypersensitivity reaction, such as anaphylaxis, and the ability to activate the emergency medical system (EMS), as necessary. Veklury must be administered by intravenous infusion. Veklury is contraindicated in patients who are allergic to Veklury or any of its components. For more information, please see the U.S. full Prescribing Information available at www.gilead.com.https://www.vekluryhcp.com/ U.S. full Prescribing Information for Veklury is available at www.gilead.com.Veklury, Gilead and the Gilead logo are registered trademarks of Gilead Sciences, Inc., or its related companies.For more information about Gilead, please visit the company’s website at www.gilead.com , follow Gilead on Twitter (@Gilead Sciences) or call Gilead Public Affairs at 1-800-GILEAD-5 or 1-650-574-3000.View source version on businesswire.com: https://www.businesswire.com/news/home/20220424005046/en/ Source: Gilead Sciences, Inc.
Gilead data shows COVID drug Veklury shows benefit if given early, cuts hospitalization risk
Apr. 25, 2022 6:27 AM ET
By: Ravikash, SA News Editor2 Comments Gilead Sciences (NASDAQ:GILD) reported data showing activity of its COVID-19 therapy Veklury (remdesivir) based on real-world results from over 850K patients, and a post-hoc analysis of a phase 3 trial.https://seekingalpha.com/news/3826055-gilead-data-shows-covid-drug-veklury-shows-benefit-if-given-early-cuts-hospitalization-risk
https://seekingalpha.com/symbol/GILD
https://www.vekluryhcp.com/https://www.gilead.com/
ENHERTU® (fam-trastuzumab deruxtecan-nxki)
ENHERTU® (fam-trastuzumab deruxtecan-nxki)
ENHERTU® (fam-trastuzumab deruxtecan-nxki)
Enhertu granted Priority Review in the US for patients with previously treated HER2-mutant metastatic non-small cell lung cancer
PUBLISHED19 April 2022 19 April 2022 07:00 BST
Based on pivotal DESTINY-Lung01 results showing AstraZeneca and Daiichi Sankyo’s Enhertu demonstrated a 54.9% tumour response rate If approved, Enhertu to provide patients with a much-needed targeted therapy option
AstraZeneca and Daiichi Sankyo have received notification of acceptance of the supplemental Biologics License Application (sBLA) of Enhertu (trastuzumab deruxtecan) for the treatment of adult patients in the US with unresectable or metastatic non-small cell lung cancer (NSCLC) whose tumours have a HER2 (ERBB2) mutation and who have received a prior systemic therapy. The application has also been granted Priority Review.Enhertu is a HER2-directed antibody drug conjugate (ADC) being jointly developed by AstraZeneca and Daiichi Sankyo.The Food and Drug Administration (FDA) grants Priority Review to applications for medicines that, if approved, would offer significant improvements over available options by demonstrating safety or efficacy improvements, preventing serious conditions, or enhancing patient compliance.1 The Prescription Drug User Fee Act (PDUFA) date, the FDA action date for their regulatory decision, is during the third quarter of 2022. The Priority Review follows Breakthrough Therapy Designation granted by the FDA for Enhertu in this cancer type in May 2020.Lung cancer is the second most common form of cancer globally, with more than two million new cases diagnosed in 2020.2 For patients with metastatic NSCLC, prognosis is particularly poor, as only approximately 8% will live beyond five years after diagnosis.3 There are currently no HER2-directed therapies approved specifically for the treatment of HER2-mutant NSCLC,4 which occurs in approximately 2-4% of patients with non-squamous NSCLC.4,5Susan Galbraith, Executive Vice President, Oncology R&D, AstraZeneca, said: “The DESTINY-Lung01 trial confirmed the HER2 mutation as an actionable biomarker in non-small cell lung cancer. If approved, Enhertu has the potential to become a new standard treatment in this patient population, offering a much-needed option for patients with HER2-mutant metastatic non-small cell lung cancer who currently have no targeted treatment options.”Ken Takeshita, MD, Global Head, R&D, Daiichi Sankyo, said: “The results of DESTINY-Lung01 showed that Enhertu is the first HER2-directed therapy to demonstrate a strong and robust tumour response in more than half of patients with previously treated HER2-mutant metastatic non-small cell lung cancer. Seeking approval in the US for a third tumour type in three years further demonstrates the significant potential of Enhertu in treating multiple HER2-targetable cancers.”The sBLA is based on data from the registrational DESTINY-Lung01 Phase II trial published in The New England Journal of Medicine, and is supported by the Phase I trial (DS8201-A-J101) published in Cancer Discovery.Primary results from previously-treated patients with HER2-mutations (cohort 2) of DESTINY-Lung01 demonstrated a confirmed objective response rate (ORR) of 54.9% (95% confidence interval [CI]: 44.2-65.4) in patients treated with Enhertu (6.4mg/kg) as assessed by independent central review (ICR). One (1.1%) complete response (CR) and 49 (53.8%) partial responses (PR) were observed.A confirmed disease control rate (DCR) of 92.3% was seen with a reduction in tumour size observed in most patients. After a median follow-up of 13.1 months, the median duration of response (DoR) for Enhertu was 9.3 months. The median progression-free survival (PFS) was 8.2 months and the median overall survival (OS) was 17.8 months.The safety profile of the most common adverse events with Enhertu in DESTINY-Lung01 was consistent with previous clinical trials with no new safety concerns identified.Enhertu is being further assessed in a comprehensive clinical development programme evaluating efficacy and safety across multiple HER2-targetable cancers, including breast, gastric, lung and colorectal cancers.
DESTINY-Lung01
DESTINY-Lung01 is a global Phase II, open-label, two-cohort trial evaluating the safety and efficacy of Enhertu in patients with HER2-mutant (6.4mg/kg) or HER2-overexpressing (defined as IHC3+ or IHC2+) [6.4mg/kg and 5.4mg/kg] unresectable and/or metastatic non-squamous NSCLC who had progressed after one or more systemic therapies. The primary endpoint is confirmed ORR by ICR. Key secondary endpoints include DoR, DCR, PFS, OS and safety. DESTINY-Lung01 enrolled approximately 180 patients at multiple sites, including Asia, Europe and North America. For more information about the trial, visit ClinicalTrials.gov.
Enhertu
Enhertu is a HER2-directed ADC. Designed using Daiichi Sankyo’s proprietary DXd ADC technology, Enhertu is the lead ADC in the oncology portfolio of Daiichi Sankyo and the most advanced programme in AstraZeneca’s ADC scientific platform. Enhertu consists of a HER2 monoclonal antibody attached to a topoisomerase I inhibitor payload, an exatecan derivative, via a stable tetrapeptide-based cleavable linker.Enhertu (5.4mg/kg) is approved in more than 40 countries for the treatment of adult patients with unresectable or metastatic HER2-positive breast cancer who have received two or more prior anti-HER2-based regimens based on the results from the DESTINY-Breast01 trial.Enhertu (6.4mg/kg) is approved in several countries for the treatment of adult patients with locally advanced or metastatic HER2-positive gastric or gastroesophageal junction (GEJ) adenocarcinoma who have received a prior trastuzumab-based regimen based on the results from the DESTINY-Gastric01 trial.https://www.enhertu.com/en/
Daiichi Sankyo collaboration
Daiichi Sankyo Company, Limited (TSE: 4568) [referred to as Daiichi Sankyo] and AstraZeneca entered into a global collaboration to jointly develop and commercialise Enhertu (a HER2-directed ADC) in March 2019, and datopotamab deruxtecan (DS-1062; a TROP2-directed ADC) in July 2020, except in Japan where Daiichi Sankyo maintains exclusive rights. Daiichi Sankyo is responsible for the manufacturing and supply of Enhertu and datopotamab deruxtecan.
Please visit astrazeneca.com and follow the Company on Twitter @AstraZeneca.
AstraZeneca, Daiichi Sankyo's Enhertu gets FDA priority review in lung cancer subtype
Apr. 19, 2022 4:36 AM ET
AstraZeneca PLC (AZN), DSNKYDSKYF
By: Ravikash, SA News Editor
- The U.S. Food and Drug Administration (FDA) granted priority review to AstraZeneca (NASDAQ:AZN) and Daiichi Sankyo's (OTCPK:DSKYF) (OTCPK:DSNKY) Enhertu to treat adult patients with unresectable or metastatic non-small cell lung cancer (NSCLC) whose tumors have a HER2 (ERBB2) mutation and who have received a prior systemic therapy.
- https://seekingalpha.com/news/3824153-astrazeneca-daiichi-sankyos-enhertu-gets-fda-priority-review-in-lung-cancer-subtype
- https://seekingalpha.com/symbol/DSNKY
- https://seekingalpha.com/symbol/DSKYF
- https://seekingalpha.com/symbol/AZN
- https://www.enhertu.com/en/
- https://www.astrazeneca.com/
Opdivo (nivolumab) with Chemotherapy
ENHERTU® (fam-trastuzumab deruxtecan-nxki)
ENHERTU® (fam-trastuzumab deruxtecan-nxki)
Neoadjuvant Opdivo (nivolumab) with Chemotherapy Significantly Improves Event-Free Survival in Patients with Resectable Non-Small Cell Lung Cancer in Phase 3 CheckMate -816 Trial
04/11/2022CATEGORY:
When administered before surgery, three cycles of Opdivo in combination with chemotherapy reduced the risk of disease recurrence, progression or death by 37% and showed an encouraging early trend in overall survivalCheckMate -816 is the first positive Phase 3 trial with an immunotherapy-based combination in the neoadjuvant setting of non-small cell lung cancer and fourth Opdivo trial to demonstrate benefit in earlier stages of cancerData featured as an oral presentation during a Clinical Trials Plenary Session at the American Association for Cancer Research Annual Meeting 2022 and simultaneously published in The New England Journal of MedicineBased on the CheckMate -816 data, Opdivo in combination with chemotherapy received U.S. Food and Drug Administration approval for the neoadjuvant treatment of certain patients with resectable non-small cell lung cancerPRINCETON, N.J.--(BUSINESS WIRE)-- Bristol Myers Squibb (NYSE: BMY) today announced results from the Phase 3 CheckMate -816 trial, which showed that neoadjuvant treatment with three cycles of Opdivo (nivolumab) in combination with chemotherapy significantly improved event-free survival (EFS), a primary endpoint, compared to chemotherapy alone in patients with resectable non-small cell lung cancer (NSCLC). With a minimum follow-up of 21.0 months, Opdivo with chemotherapy reduced the risk of disease recurrence, progression or death by 37% (Hazard Ratio [HR] 0.63; 97.38% Confidence Interval [CI]: 0.43 to 0.91; p=0.0052) across randomized patients when administered before surgery. In patients receiving the combination, median EFS was 31.6 months, compared to 20.8 months for patients treated with chemotherapy alone.Additionally, while the data are still immature and the analysis did not reach statistical significance, favorable early overall survival (OS) results were observed with Opdivo in combination with chemotherapy (HR 0.57; 99.67% CI: 0.30 to 1.07). At two years, 83% of patients treated with neoadjuvant Opdivo and chemotherapy were alive, compared to 71% with chemotherapy alone. OS will continue to be followed for upcoming analyses.CheckMate -816 represents the first Phase 3 study with an immunotherapy-based combination to show a significant improvement in EFS, as well as in the other primary endpoint of pathologic complete response (pCR), in the neoadjuvant setting of NSCLC. The EFS data are being presented for the first time during the Neoadjuvant and Perioperative Immunotherapy Clinical Trials Plenary Session (Abstract #CT012) at the American Association for Cancer Research (AACR) Annual Meeting 2022 on Monday, April 11, 2022, from 10:15 a.m. to 12:15 p.m. CT and simultaneously published in The New England Journal of Medicine.“While resectable non-small cell lung cancer may be curable in some cases, patients face a high probability of recurrence after surgery, so we need effective systemic treatment options to interrupt this trajectory,” said Nicolas Girard, M.D., Ph.D., CheckMate -816 investigator and professor and head of the Thorax Institute Curie-Montsouris. “The results from CheckMate -816 represent the first demonstration of clear and significant benefits with neoadjuvant immunotherapy-based treatment over chemotherapy alone for these patients, initially seen with increased pathologic complete response and now with improved event-free survival and a positive trend in overall survival. As we work toward the ultimate goal of curing these patients, these data suggest the potential for better long-term outcomes with nivolumab in combination with chemotherapy.”In the study, the safety profile of the neoadjuvant Opdivo-chemotherapy combination was consistent with previous reports, and no new safety signals were observed at the time of the EFS analysis. Rates of Grade 3-4 treatment-related adverse events were similar with the Opdivo-chemotherapycombination versus chemotherapy alone (34% vs. 37%), as were all causality surgery-related Grade 3-4 adverse events (11% with the combination vs. 15% with chemotherapy). With Opdivo in combination with chemotherapy, 83% of patients went on to receive surgery, compared to 75% with chemotherapy.“Surgery is still the cornerstone of cure for patients with non-small cell lung cancer,” said Jonathan Spicer M.D., Ph.D., CheckMate -816 investigator; associate professor of surgery, McGill University; and attending surgeon, division of thoracic and upper gastrointestinal surgery, Montreal General Hospital, McGill University Health Centre. “The fact that neoadjuvant nivolumab with chemotherapy enabled shorter, less invasive and less extensive operations without increasing complications or adverse events is of tremendous importance to thoracic surgeons and their patients. These findings, combined with the improved survival outcomes, have the potential to completely change the way surgeons and oncologists collaborate in treating patients with resectable non-small cell lung cancer.”“Immunotherapy has ushered in a new era of treatment in metastatic cancers, changing survival expectations for patients with lung cancer and many other tumor types. More recently, our understanding of the biology of the immune system and cancer has led us to explore the role of immunotherapy in the neoadjuvant, adjuvant and peri-operative settings,” said Abderrahim Oukessou, M.D., vice president, thoracic cancers development lead, Bristol Myers Squibb. “The data from CheckMate -816, including the positive early overall survival results, reinforce the importance of researching immunotherapy in earlier stages of disease, and we look forward to continuing to see this science translate into tangible benefits for patients and their families.”Based on the EFS and pCR results from CheckMate -816,the U.S. Food and Drug Administration approved Opdivo in combination with platinum-doublet chemotherapy every three weeks for three cycles for adult patients with resectable (tumors ≥4 cm or node positive) NSCLC in the neoadjuvant setting in March 2022, and further applications are under review with health authorities globally.In non-metastatic NSCLC, Bristol Myers Squibb and collaborators are exploring the use of immunotherapy in the neoadjuvant, adjuvant and peri-operative settings, as well as in association with chemoradiation. The scientific rationale for using immunotherapy in the neoadjuvant setting is twofold: the presence of a tumor during immunotherapy treatment may enable a stronger immune response, potentially making the treatment more effective against a primary tumor, while offering an early opportunity to target covert micro-metastasis. To date, Opdivo-based treatments have shown improved efficacy in the neoadjuvant or adjuvant treatment of four tumor types: lung cancer, bladder cancer, esophageal/gastroesophageal junction cancer and melanoma.Bristol Myers Squibb thanks the patients and investigators involved in the CheckMate -816 clinical trial.
About CheckMate -816
CheckMate -816 is a Phase 3 randomized, open label, multi-center trial evaluating Opdivo in combination with chemotherapy compared to chemotherapy alone as neoadjuvant treatment in patients with resectable stage IB to IIIA non-small cell lung cancer (per the 7th edition American Joint Committee on Cancer/Union for International Cancer Control staging criteria), regardless of PD-L1 expression. For the primary analysis, 358 patients were randomized to receive either Opdivo 360 mg with histology-based platinum doublet chemotherapy every three weeks for three cycles, or platinum doublet chemotherapy every three weeks for three cycles, followed by surgery. The primary endpoints of the trial are event-free survival and pathologic complete response. Secondary endpoints include overall survival, major pathologic response, and time to death or distant metastases.
About Opdivo
Opdivo is a programmed death-1 (PD-1) immune checkpoint inhibitor that is designed to uniquely harness the body’s own immune system to help restore anti-tumor immune response. By harnessing the body’s own immune system to fight cancer, Opdivo has become an important treatment option across multiple cancers.Opdivo’s leading global development program is based on Bristol Myers Squibb’s scientific expertise in the field of Immuno-Oncology, and includes a broad range of clinical trials across all phases, including Phase 3, in a variety of tumor types. To date, the Opdivo clinical development program has treated more than 35,000 patients. The Opdivo trials have contributed to gaining a deeper understanding of the potential role of biomarkers in patient care, particularly regarding how patients may benefit from Opdivo across the continuum of PD-L1 expression.In July 2014, Opdivo was the first PD-1 immune checkpoint inhibitor to receive regulatory approval anywhere in the world. Opdivo is currently approved in more than 65 countries, including the United States, the European Union, Japan and China. In October 2015, the Company’s Opdivo and Yervoy combination regimen was the first Immuno-Oncology to receive regulatory approval for the treatment of metastatic melanoma and is currently approved in more than 50 countries, including the United States and the European Union.
INDICATIONS
OPDIVO® (nivolumab), as a single agent, is indicated for the treatment of adult patients with unresectable or metastatic melanoma.OPDIVO® (nivolumab), in combination with YERVOY® (ipilimumab), is indicated for the treatment of adult patients with unresectable or metastatic melanoma.OPDIVO® (nivolumab) is indicated for the adjuvant treatment of adult patients with melanoma with involvement of lymph nodes or metastatic disease who have undergone complete resection.OPDIVO® (nivolumab), in combination with platinum-doublet chemotherapy, is indicated as neoadjuvant treatment of adult patients with resectable (tumors ≥4 cm or node positive) non-small cell lung cancer (NSCLC).OPDIVO® (nivolumab), in combination with YERVOY® (ipilimumab), is indicated for the first-line treatment of adult patients with metastatic non-small cell lung cancer (NSCLC) whose tumors express PD-L1 (≥1%) as determined by an FDA-approved test, with no EGFR or ALK genomic tumor aberrations.OPDIVO® (nivolumab), in combination with YERVOY® (ipilimumab) and 2 cycles of platinum-doublet chemotherapy, is indicated for the first-line treatment of adult patients with metastatic or recurrent non-small cell lung cancer (NSCLC), with no EGFR or ALK genomic tumor aberrations.OPDIVO® (nivolumab) is indicated for the treatment of adult patients with metastatic non-small cell lung cancer (NSCLC) with progression on or after platinum-based chemotherapy. Patients with EGFR or ALK genomic tumor aberrations should have disease progression on FDA-approved therapy for these aberrations prior to receiving OPDIVO.OPDIVO® (nivolumab), in combination with YERVOY® (ipilimumab), is indicated for the first-line treatment of adult patients with unresectable malignant pleural mesothelioma (MPM).OPDIVO® (nivolumab), in combination with YERVOY® (ipilimumab), is indicated for the first-line treatment of adult patients with intermediate or poor risk advanced renal cell carcinoma (RCC).OPDIVO® (nivolumab), in combination with cabozantinib, is indicated for the first-line treatment of adult patients with advanced renal cell carcinoma (RCC).OPDIVO® (nivolumab) is indicated for the treatment of adult patients with advanced renal cell carcinoma (RCC) who have received prior anti-angiogenic therapy.OPDIVO® (nivolumab) is indicated for the treatment of adult patients with classical Hodgkin lymphoma (cHL) that has relapsed or progressed after autologous hematopoietic stem cell transplantation (HSCT) and brentuximab vedotin or after 3 or more lines of systemic therapy that includes autologous HSCT. This indication is approved under accelerated approval based on overall response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.OPDIVO® (nivolumab) is indicated for the treatment of adult patients with recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN) with disease progression on or after platinum-based therapy.OPDIVO® (nivolumab) is indicated for the treatment of adult patients with locally advanced or metastatic urothelial carcinoma who have disease progression during or following platinum-containing chemotherapy or have disease progression within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy.OPDIVO® (nivolumab), as a single agent, is indicated for the adjuvant treatment of adult patients with urothelial carcinoma (UC) who are at high risk of recurrence after undergoing radical resection of UC.OPDIVO® (nivolumab), as a single agent, is indicated for the treatment of adult and pediatric (12 years and older) patients with microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) metastatic colorectal cancer (CRC) that has progressed following treatment with a fluoropyrimidine, oxaliplatin, and irinotecan. This indication is approved under accelerated approval based on overall response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.OPDIVO® (nivolumab), in combination with YERVOY® (ipilimumab), is indicated for the treatment of adults and pediatric patients 12 years and older with microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) metastatic colorectal cancer (CRC) that has progressed following treatment with a fluoropyrimidine, oxaliplatin, and irinotecan. This indication is approved under accelerated approval based on overall response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.OPDIVO® (nivolumab), in combination with YERVOY® (ipilimumab), is indicated for the treatment of adult patients with hepatocellular carcinoma (HCC) who have been previously treated with sorafenib. This indication is approved under accelerated approval based on overall response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.OPDIVO® (nivolumab) is indicated for the treatment of adult patients with unresectable advanced, recurrent or metastatic esophageal squamous cell carcinoma (ESCC) after prior fluoropyrimidine- and platinum-based chemotherapy.OPDIVO® (nivolumab) is indicated for the adjuvant treatment of completely resected esophageal or gastroesophageal junction cancer with residual pathologic disease in adult patients who have received neoadjuvant chemoradiotherapy (CRT).OPDIVO® (nivolumab), in combination with fluoropyrimidine- and platinum- containing chemotherapy, is indicated for the treatment of adult patients with advanced or metastatic gastric cancer, gastroesophageal junction cancer, and esophageal adenocarcinoma.
https://www.opdivo.com/
Please see US Full Prescribing Information for OPDIVO and YERVOY.
Source: Bristol Myers Squibb
Bristol Myers highlights potential of Opdivo when used before surgery in lung cancer
Apr. 11, 2022 12:34 PM ET
Bristol-Myers Squibb Company (BMY)
By: Dulan Lokuwithana, SA News Editor Announcing Phase 3 data from its CheckMate -816 trial, Bristol Myers Squibb (NYSE:BMY) announced on Monday that its immune checkpoint inhibitor, Opdivo, “significantly improved” event-free survival (EFS) in lung cancer when administered with chemotherapy before surgery. https://seekingalpha.com/news/3822396-bristol-myers-says-opdivo-was-effective-when-used-before-surgery-in-lung-cancer
https://seekingalpha.com/symbol/BMY
https://www.opdivo.com/https://www.bms.com/
DUPIXENT® (DUPILUMAB)
DUPIXENT® (DUPILUMAB)
DUPIXENT® (DUPILUMAB)
April 7, 2022 at 12:59 AM EDT Back
DUPIXENT® (DUPILUMAB) APPROVED BY EUROPEAN COMMISSION FOR CHILDREN AGED 6 TO 11 YEARS WITH SEVERE ASTHMA WITH TYPE 2 INFLAMMATION
Approval based on Phase 3 data showing Dupixent significantly reduced severe asthma attacks and also improved lung function and health-related quality of life for childrenData reinforce well-established safety profile of Dupixent
TARRYTOWN, N.Y. and PARIS, April 7, 2022 /PRNewswire/ -- Regeneron Pharmaceuticals, Inc. (NASDAQ: REGN) and Sanofi today announced that the European Commission (EC) has expanded the marketing authorization for Dupixent® (dupilumab) in the European Union. Dupixent is now also approved in children aged 6 to 11 years as an add-on maintenance treatment for severe asthma with type 2 inflammation characterized by raised blood eosinophils and/or raised fractional exhaled nitric oxide (FeNO), who are inadequately controlled with medium to high dose inhaled corticosteroids (ICS) plus another medicinal product for maintenance treatment."Today's approval in Europe recognizes the benefits of Dupixent in helping children living with the profound effects of severe asthma, including unpredictable asthma attacks, routine disruption to daily activities and the use of systemic steroids that can impede children's growth," said George D. Yancopoulos, M.D., Ph.D., President and Chief Scientific Officer at Regeneron. "Dupixent is the only treatment available that specifically blocks two key drivers of type 2 inflammation, IL-4 and IL-13, which our trials show plays a major role in childhood asthma, as well as in related conditions such as chronic rhinosinusitis with nasal polyposis and the often co-morbid condition, atopic dermatitis. In clinical trials, Dupixent significantly reduced asthma attacks, helped children breathe better and improved their health-related quality of life. We also remain committed to investigating Dupixent in other conditions where type 2 inflammation may significantly impact patients' lives, including eosinophilic esophagitis, prurigo nodularis and chronic spontaneous urticaria."Asthma is one of the most common chronic diseases in children. Up to 85% of children with asthma may have type 2 inflammation and are more likely to have higher disease burden. Despite treatment with current standard-of-care ICS and bronchodilators, these children may continue to experience serious symptoms such as coughing, wheezing and difficulty breathing. Severe asthma may impact children's developing airways and cause potentially life-threatening exacerbations. Children with severe asthma also may require the use of multiple courses of systemic corticosteroids that carry significant risks. Uncontrolled severe asthma can interfere with day-to-day activities, like sleeping, attending school and playing sports.Dupixent, which was invented using Regeneron's proprietary VelocImmune® technology, is a fully human monoclonal antibody that inhibits the signaling of the interleukin-4 (IL-4) and interleukin-13 (IL-13) pathways and is not an immunosuppressant. By demonstrating significant clinical benefit together with a decrease in type 2 inflammation following IL-4 and IL-13 blockade with Dupixent, the Dupixent Phase 3 clinical program has established that IL-4 and IL-13 are key drivers of the type 2 inflammation that plays a major role in multiple related and often co-morbid diseases for which Dupixent is approved including asthma, atopic dermatitis and chronic rhinosinusitis with nasal polyposis (CRSwNP), as well as investigational diseases such as eosinophilic esophagitis and prurigo nodularis, which have been studied in Phase 3 trials."We are excited to bring the well-established safety and efficacy profile of Dupixent to even younger patients living with uncontrolled severe asthma in Europe. In addition to greatly reducing severe asthma attacks and improving lung function, patients in our clinical trials also reduced their oral corticosteroid use. This is particularly meaningful as these are medicines that can carry significant safety risks if used long term," said Naimish Patel, M.D. Head of Global Development, Immunology and Inflammation at Sanofi. "This approval underscores our continued commitment to bringing Dupixent to as many patients as possible suffering from the negative effects of severe asthma with the hope of improving their quality of life." The EC decision is based on pivotal data from the Phase 3 VOYAGE trial evaluating the efficacy and safety of Dupixent combined with standard-of-care asthma therapy in 408 children with uncontrolled moderate-to-severe asthma.Two pre-specified populations with evidence of type 2 inflammation were evaluated for the primary analysis: 1) patients with baseline blood eosinophils (EOS) ≥300 cells/μl (n=259) and 2) patients with either baseline FeNO ≥20 parts per billion (ppb) or baseline blood EOS ≥150 cells/μl (n=350). Patients who added Dupixent to standard-of-care in these two groups, respectively, experienced:
- Substantially reduced rates of severe asthma attacks, with a 65% and 59% average reduction over one year compared to placebo (0.24 and 0.31 events per year for Dupixent vs. 0.67 and 0.75 for placebo, respectively).
- Improved lung function observed as early as two weeks and sustained for up to 52 weeks, measured by percent predicted FEV1 (FEV1pp).
- At 12 weeks, patients taking Dupixent improved their lung function by 5.32 and 5.21 percentage points compared to placebo, respectively.
- Improved asthma control, with 81% and 79% of patients reporting a clinically meaningful improvement at 24 weeks, based on disease symptoms and impact compared to 64% and 69% of placebo patients, respectively.
- Improved health-related quality of life, with 73% and 73% of patients reporting a clinically meaningful improvement at 24 weeks, compared to 63% and 65% of placebo patients, respectively.
- Reduced systemic corticosteroid use by an average of 66% and 59% over one year compared to placebo (0.27 and 0.35 courses per year for Dupixent vs. 0.81 and 0.86 for placebo, respectively).
The safety results from the trial were generally consistent with the known safety profile of Dupixent in patients aged 12 years and older with uncontrolled moderate-to-severe asthma. The overall rates of adverse events were 83% for Dupixent and 80% for placebo. Adverse events that were more commonly observed with Dupixent compared to placebo included injection site reactions (18% Dupixent, 13% placebo), viral upper respiratory tract infections (12% Dupixent, 10% placebo) and eosinophilia (7% Dupixent, 1% placebo). Helminth infections were also more commonly observed with Dupixent in patients aged 6 to 11 years and were reported in 2% of Dupixent patients and 0% of placebo patients.
About the LIBERTY ASTHMA VOYAGE Trial
The Phase 3 randomized, double-blind, placebo-controlled trial evaluated the efficacy and safety of Dupixent (100 mg or 200 mg every two weeks, based on weight tier) combined with standard-of-care asthma therapy in 408 children aged 6 to 11 years with uncontrolled moderate-to-severe asthma. More than 90% of children in the trial had at least one concurrent atopic medical condition such as allergic rhinitis and atopic dermatitis.The primary endpoint was the annualized rate of severe asthma exacerbations over one year, and the key secondary endpoint was the change from baseline in percentage of predicted pre-bronchodilator FEV1 (FEV1pp) at week 12. The FEV1pp seeks to evaluate a patient's change in lung function compared to their predicted lung function based on age, height, sex and ethnicity to account for children's growing lung capacity at different stages of development. Additional secondary endpoints included responder rates for asthma control as measured by a ≥0.5 improvement on the Asthma Control Questionnaire-7 Interviewer Administered (ACQ-7-IA; 7-point scale) and health-related quality of life as measured by a ≥0.5 improvement on the Pediatric Asthma Quality of Life Questionnaire with Standardized Activities-Interviewer Administered (PAQLQ(S)-IA; 7-point scale).
About Dupixent
Dupixent is also approved in Europe, U.S., Japan and other countries around the world for use in certain patients with asthma, specific patients with moderate-to-severe atopic dermatitis as well as CRSwNP in different age populations. Dupixent is also approved in one or more of these indications in more than 60 countries around the world, and more than 400,000 patients have been treated globally.Dupixent is an injection under the skin (subcutaneous injection) at different injection sites. In the EU for pediatric patients aged 6 to 11 years, Dupixent dosing is based on weight tier (100 mg every two weeks or 300 mg every four weeks for children ≥15 to <30 kg, 200 mg every two weeks or 300 mg every four weeks for children ≥30 to <60 kg and 200 mg every two weeks for children ≥60 kg) and is supplied as a pre-filled syringe. It is also available as a pre-filled pen for adolescents (12 to 17 years) and adults at 200 and 300 mg doses. Dupixent is intended for use under the guidance of a healthcare professional and can be given in a clinic or at home by self-administration after training by a healthcare professional. In children younger than 12 years of age, Dupixent should be administered by a caregiver if given at home.https://www.dupixent.com/
U.S. Indications
DUPIXENT is a prescription medicine used:
- to treat adults and children 6 years of age and older with moderate-to-severe atopic dermatitis (eczema) that is not well controlled with prescription therapies used on the skin (topical), or who cannot use topical therapies. DUPIXENT can be used with or without topical corticosteroids. It is not known if DUPIXENT is safe and effective in children with atopic dermatitis under 6 years of age.
- with other asthma medicines for the maintenance treatment of moderate-to-severe eosinophilic or oral steroid dependent asthma in adults and children 6 years of age and older whose asthma is not controlled with their current asthma medicines. DUPIXENT helps prevent severe asthma attacks (exacerbations) and can improve your breathing. DUPIXENT may also help reduce the amount of oral corticosteroids you need while preventing severe asthma attacks and improving your breathing. DUPIXENT is not used to treat sudden breathing problems. It is not known if DUPIXENT is safe and effective in children with asthma under 6 years of age.
- with other medicines for the maintenance treatment of chronic rhinosinusitis with nasal polyposis (CRSwNP) in adults whose disease is not controlled. It is not known if DUPIXENT is safe and effective in children with chronic rhinosinusitis with nasal polyposis under 18 years of age.
Please see accompanying full Prescribing Information including Patient Information.
For additional information about the company, please visit www.regeneron.com or follow @Regeneron on Twitter. View original content:https://www.prnewswire.com/news-releases/dupixent-dupilumab-approved-by-european-commission-for-children-aged-6-to-11-years-with-severe-asthma-with-type-2-inflammation-301519649.htmlSOURCE Regeneron Pharmaceuticals, Inc.
Regeneron, Sanofi win EU approval for Dupixent in younger children with asthma
Apr. 07, 2022 9:27 AM ET
Regeneron Pharmaceuticals, Inc. (REGN), SNY
By: Dulan Lokuwithana, SA News Editor
- The European Union (EU) has expanded the approval of Dupixent, allowing its use as an add-on maintenance treatment for severe asthma in certain patients aged 6 to 11 years, the developers, Regeneron (NASDAQ:REGN) and Sanofi (NASDAQ:SNY) announced on Thursday.
- https://seekingalpha.com/news/3821670-regeneron-sanofi-win-eu-nod-for-dupixent-in-younger-children-with-asthma
- https://seekingalpha.com/symbol/SNY
- https://seekingalpha.com/symbol/REGN
- https://www.regeneron.com/
- https://www.dupixent.com/
Opdivo (nivolumab)
DUPIXENT® (DUPILUMAB)
DUPIXENT® (DUPILUMAB)
Bristol Myers Squibb Receives European Commission Approval for Opdivo (nivolumab) as Adjuvant Treatment for Patients with Radically Resected, High-Risk Muscle-Invasive Urothelial Carcinoma with Tumor Cell PD-L1 Expression ≥1%
04/05/2022
CATEGORY: Corporate/Financial News
Approval based on Phase 3 CheckMate -274 trial results showing that adjuvant treatment with Opdivo significantly reduced patients’ risk of disease recurrence or death compared to placeboOpdivo is now the first and only adjuvant immunotherapy option approved in this setting in the European UnionDecision marks the third approval for Opdivo in earlier stages of cancer in the European Union, following melanoma and esophageal/gastroesophageal junction cancer
PRINCETON, N.J.--(BUSINESS WIRE)-- Bristol Myers Squibb (NYSE: BMY) today announced that the European Commission (EC) has approved Opdivo (nivolumab) for the adjuvant treatment of adults with muscle-invasive urothelial carcinoma with tumor cell PD-L1 expression ≥1% who are at a high risk of recurrence after undergoing radical resection.
With this EC decision, Opdivo becomes the first adjuvant immunotherapy option approved for patients in the European Union (EU) in this setting.
In the Phase 3 CheckMate -274 trial, Opdivo demonstrated a statistically significant and clinically meaningful improvement in disease-free survival (DFS) compared to placebo in both all-randomized patients and in patients whose tumor cells express PD-L1 ≥1%. The EC decision is based on the results in patients with tumor cell PD-L1 expression ≥1%, which showed a 47% reduction in the risk of disease recurrence or death with Opdivo vs. placebo (Hazard Ratio [HR] 0.53; 95% Confidence Interval [CI]: 0.38 to 0.75; p=0.0005), with median DFS not reached with Opdivo compared to 8.41 months with placebo. Opdivo was generally well tolerated, with a safety profile that was consistent with previously reported Opdivo studies in patients with solid tumors.“For years, patients with muscle-invasive urothelial carcinoma have lived with the unfortunate reality that, despite being diagnosed early enough to have their cancer removed, around half will face disease recurrence, with few safe and effective treatment options available to help prevent this cycle,” said Fred Witjes, M.D., professor of oncological urology, Radboud Institute for Molecular Life Sciences. “With the approval of nivolumab, clinicians will now have an immunotherapy treatment option to offer certain patients after surgery that, in the CheckMate -274 clinical trial, significantly reduced the risk of disease recurrence or death. This approval has the potential to transform the way we treat muscle-invasive urothelial carcinoma for appropriate patients in the European Union.”The EC approval allows for the use of Opdivo for the adjuvant treatment of adults with radically resected, high-risk muscle-invasive urothelial carcinoma whose tumor cells express PD-L1 ≥1%inthe 27 member states of the EU, as well as Iceland, Liechtenstein and Norway. In addition to the EU, Opdivo has received approvals based on the CheckMate -274 trial in seven countries, including indications regardless of PD-L1 expression levels in the United States and Japan, and further applications are under review with health authorities globally. Results from CheckMate -274 were first presented at the American Society of Clinical Oncology (ASCO) Genitourinary Symposium in February 2021 and published in the New England Journal of Medicine in June 2021.“We are driven by the goal of advancing new treatment options that can help change the outlook for patients with cancer, whether they are diagnosed at an earlier stage or with metastatic disease,” said Dana Walker, M.D., M.S.C.E., vice president, development program lead, genitourinary cancers, Bristol Myers Squibb. “This approval for Opdivo gives us the opportunity to introduce a new post-surgery standard of care for certain patients with urothelial cancer, building on our legacy as the first company to bring immune checkpoint inhibitors to patients in the European Union in the adjuvant settings of melanoma and esophageal cancers. We look forward to working with European stakeholders to make Opdivo available to eligible patients as soon as possible.”“With the second highest incidence of bladder cancer globally, Europe has had a pressing need for new treatment options for patients after surgery, who are managing the physical and mental impacts of surgery combined with the fear of their cancer returning,” said Alex Filicevas, executive director, World Bladder Cancer Patient Coalition. “We are pleased to see the approval of a new adjuvant treatment that has the potential to help reduce the risk of recurrence for patients. Additionally, undergoing surgical removal of the bladder for muscle-invasive bladder cancer is life-altering, making it all the more important that published data show nivolumab maintained quality of life compared to placebo. This positive decision may have the potential to give people with muscle-invasive urothelial carcinoma more good quality time with their loved ones.”Opdivo has now been approved for the adjuvant treatment of three different carcinoma types in the EU: urothelial carcinoma, melanoma and esophageal/gastroesophageal junction cancer. In addition, the company has a broad development program in earlier stages of cancer that currently spans eight different tumor types across the neoadjuvant, adjuvant and peri-operative settings.
About CheckMate -274
CheckMate -274 is a Phase 3 randomized, double-blind, multi-center study evaluating Opdivo compared to placebo in patients with muscle-invasive urothelial carcinoma at a high risk of recurrence after radical resection. A total of 709 patients were randomized 1:1 to receive Opdivo 240 mg or placebo every two weeks for up to one year. The primary endpoints of the trial are disease-free survival (DFS) in all randomized patients (i.e., the intention-to-treat population) and in the subset of patients whose tumor cells express PD-L1 ≥1%. Key secondary endpoints include overall survival (OS), non-urothelial tract recurrence-free survival (NUTRFS) and disease-specific survival (DSS).
About Opdivo
Opdivo is a programmed death-1 (PD-1) immune checkpoint inhibitor that is designed to uniquely harness the body’s own immune system to help restore anti-tumor immune response. By harnessing the body’s own immune system to fight cancer, Opdivo has become an important treatment option across multiple cancers.Opdivo’s leading global development program is based on Bristol Myers Squibb’s scientific expertise in the field of Immuno-Oncology, and includes a broad range of clinical trials across all phases, including Phase 3, in a variety of tumor types. To date, the Opdivo clinical development program has treated more than 35,000 patients. The Opdivo trials have contributed to gaining a deeper understanding of the potential role of biomarkers in patient care, particularly regarding how patients may benefit from Opdivo across the continuum of PD-L1 expression.In July 2014, Opdivo was the first PD-1 immune checkpoint inhibitor to receive regulatory approval anywhere in the world. Opdivo is currently approved in more than 65 countries, including the United States, the European Union, Japan and China. In October 2015, the Company’s Opdivo and Yervoy combination regimen was the first Immuno-Oncology to receive regulatory approval for the treatment of metastatic melanoma and is currently approved in more than 50 countries, including the United States and the European Union.
U.S. FDA-Approved Indications
OPDIVO® (nivolumab), as a single agent, is indicated for the treatment of adult patients with unresectable or metastatic melanoma.OPDIVO® (nivolumab), in combination with YERVOY® (ipilimumab), is indicated for the treatment of adult patients with unresectable or metastatic melanoma.OPDIVO® (nivolumab) is indicated for the adjuvant treatment of adult patients with melanoma with involvement of lymph nodes or metastatic disease who have undergone complete resection.OPDIVO® (nivolumab), in combination with platinum-doublet chemotherapy, is indicated as neoadjuvant treatment of adult patients with resectable (tumors ≥4 cm or node positive) non-small cell lung cancer (NSCLC).OPDIVO® (nivolumab), in combination with YERVOY® (ipilimumab), is indicated for the first-line treatment of adult patients with metastatic non-small cell lung cancer (NSCLC) whose tumors express PD-L1 (≥1%) as determined by an FDA-approved test, with no EGFR or ALK genomic tumor aberrations.OPDIVO® (nivolumab), in combination with YERVOY® (ipilimumab) and 2 cycles of platinum-doublet chemotherapy, is indicated for the first-line treatment of adult patients with metastatic or recurrent non-small cell lung cancer (NSCLC), with no EGFR or ALK genomic tumor aberrations.OPDIVO® (nivolumab) is indicated for the treatment of adult patients with metastatic non-small cell lung cancer (NSCLC) with progression on or after platinum-based chemotherapy. Patients with EGFR or ALK genomic tumor aberrations should have disease progression on FDA-approved therapy for these aberrations prior to receiving OPDIVO.OPDIVO® (nivolumab), in combination with YERVOY® (ipilimumab), is indicated for the first-line treatment of adult patients with unresectable malignant pleural mesothelioma (MPM).OPDIVO® (nivolumab), in combination with YERVOY® (ipilimumab), is indicated for the first-line treatment of adult patients with intermediate or poor risk advanced renal cell carcinoma (RCC).OPDIVO® (nivolumab), in combination with cabozantinib, is indicated for the first-line treatment of adult patients with advanced renal cell carcinoma (RCC).OPDIVO® (nivolumab) is indicated for the treatment of adult patients with advanced renal cell carcinoma (RCC) who have received prior anti-angiogenic therapy.OPDIVO® (nivolumab) is indicated for the treatment of adult patients with classical Hodgkin lymphoma (cHL) that has relapsed or progressed after autologous hematopoietic stem cell transplantation (HSCT) and brentuximab vedotin or after 3 or more lines of systemic therapy that includes autologous HSCT. This indication is approved under accelerated approval based on overall response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.OPDIVO® (nivolumab) is indicated for the treatment of adult patients with recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN) with disease progression on or after platinum-based therapy.OPDIVO® (nivolumab) is indicated for the treatment of adult patients with locally advanced or metastatic urothelial carcinoma who have disease progression during or following platinum-containing chemotherapy or have disease progression within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy.OPDIVO® (nivolumab), as a single agent, is indicated for the adjuvant treatment of adult patients with urothelial carcinoma (UC) who are at high risk of recurrence after undergoing radical resection of UC.OPDIVO® (nivolumab), as a single agent, is indicated for the treatment of adult and pediatric (12 years and older) patients with microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) metastatic colorectal cancer (CRC) that has progressed following treatment with a fluoropyrimidine, oxaliplatin, and irinotecan. This indication is approved under accelerated approval based on overall response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.OPDIVO® (nivolumab), in combination with YERVOY® (ipilimumab), is indicated for the treatment of adults and pediatric patients 12 years and older with microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) metastatic colorectal cancer (CRC) that has progressed following treatment with a fluoropyrimidine, oxaliplatin, and irinotecan. This indication is approved under accelerated approval based on overall response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.OPDIVO® (nivolumab), in combination with YERVOY® (ipilimumab), is indicated for the treatment of adult patients with hepatocellular carcinoma (HCC) who have been previously treated with sorafenib. This indication is approved under accelerated approval based on overall response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.OPDIVO® (nivolumab) is indicated for the treatment of adult patients with unresectable advanced, recurrent or metastatic esophageal squamous cell carcinoma (ESCC) after prior fluoropyrimidine- and platinum-based chemotherapy.OPDIVO® (nivolumab) is indicated for the adjuvant treatment of completely resected esophageal or gastroesophageal junction cancer with residual pathologic disease in adult patients who have received neoadjuvant chemoradiotherapy (CRT).OPDIVO® (nivolumab), in combination with fluoropyrimidine- and platinum- containing chemotherapy, is indicated for the treatment of adult patients with advanced or metastatic gastric cancer, gastroesophageal junction cancer, and esophageal adenocarcinoma.https://www.opdivo.com/
For more information about Bristol Myers Squibb, visit us at BMS.com or follow us on LinkedIn, Twitter, YouTube, Facebook and Instagram.
Bristol Myers Squibb Receives European Commission Approval for Opdivo (nivolumab) with Chemotherapy as First-Line Treatment for Patients with...
04/05/2022
CATEGORY:
Opdivo with chemotherapy demonstrated statistically significant and clinically meaningful improvement in overall survival compared to chemotherapy alone in this patient population; approval based on Phase 3 results from the CheckMate -648 trialOpdivo plus Yervoy also received EC approval for the same indicationPRINCETON, N.J.--(BUSINESS WIRE)-- Bristol Myers Squibb Receives European Commission Approval for Opdivo (nivolumab) with Chemotherapy as First-Line Treatment for Patients with Unresectable Advanced, Recurrent or Metastatic Esophageal Squamous Cell Carcinoma with Tumor Cell PD-L1 Expression ≥ 1%
Bristol Myers Squibb (NYSE: BMY) today announced that the European Commission (EC) has approved Opdivo (nivolumab) in combination with fluoropyrimidine- and platinum-based chemotherapy for the first-line treatment of adult patients with unresectable advanced, recurrent or metastatic esophageal squamous cell carcinoma (ESCC) with tumor cell PD-L1 expression ≥ 1%. The EC’s decision is based on results from the Phase 3 CheckMate -648 trial, in which Opdivo with chemotherapy demonstrated a statistically significant and clinically meaningful overall survival (OS) benefit compared to chemotherapy alone at the pre-specified interim analysis. The safety profile of Opdivo with chemotherapy was consistent with previously reported studies. Results from CheckMate -648 were presented at the American Society of Clinical Oncology (ASCO) Annual Meeting in June 2021.“This approval is an important advancement for patients in the EU, especially given the highly aggressive nature of advanced ESCC,” said Ian M. Waxman, M.D., development lead, gastrointestinal cancers, Bristol Myers Squibb. “Opdivo with chemotherapy is now one of two newly approved Opdivo-based combinations to show superior overall survival benefit compared to chemotherapy alone, offering higher hopes for patients with unresectable advanced, recurrent or metastatic ESCC with tumor cell PD-L1 expression ≥ 1%. We are eager to introduce this new treatment option to patients in the European Union and potentially improve their survival outcomes.”The EC has also approved Opdivo in combination with Yervoy (ipilimumab) for the first-line treatment of adult patients with unresectable advanced, recurrent or metastatic esophageal squamous cell carcinoma (ESCC) with tumor cell PD-L1 expression ≥ 1%.The EC approval allows for the use of Opdivo with fluoropyrimidine- and platinum-based combination chemotherapy for the first-line treatment of adults with unresectable advanced, recurrent or metastatic ESCC with tumor cell PD-L1 expression ≥ 1% in the 27 member states of the European Union, as well as Iceland, Liechtenstein and Norway.
CheckMate -648 Efficacy and Safety Results
Results from CheckMate -648 include:
- OS in participants with tumor cell PD-L1 expression ≥ 1%. (primary endpoint): Median OS was 15.44 months (95% Confidence Interval [CI]: 11.93, 19.52) for nivolumab with chemotherapy vs. 9.07 months (95% CI: 7.69, 9.95) for chemotherapy (Hazard Ratio [HR] = 0.54; 95% CI: 0.37, 0.80; p= <0.0001).
- PFS in participants with tumor cell PD-L1 expression ≥ 1%. (primary endpoint): Median PFS was 6.93 months (95% CI: 5.68, 8.34) for nivolumab with chemotherapy vs. 4.44 months (95% CI: 2.89, 5.82) for chemotherapy (HR = 0.65; 95% CI: 0.46, 0.92; p=0.0023)
- ORR (secondary endpoint): The ORR was 53.2% (95% CI: 45.1, 61.1) for nivolumab with chemotherapy vs. 19.7% (95% CI: 13.8, 26.8) for chemotherapy.
- Safety (based on pooled data across tumor types): Incidence of Grade 3-5 adverse reactions was 76% for nivolumab with chemotherapy and 62% for chemotherapy alone, with 1.4% fatal adverse reactions attributed to nivolumab in combination with chemotherapy including pneumonia, febrile neutropenia, thrombosis, pneumonitis, diarrhea, and renal failure. Median duration of therapy was 6.44 months (95% CI: 5.95, 6.80) for nivolumab with chemotherapy and 4.34 months (95% CI: 4.04, 4.70) for chemotherapy.
About CheckMate -648
CheckMate -648 is a randomized Phase 3 study evaluating Opdivo plus Yervoy (N=325) or Opdivo with fluorouracil and cisplatin (N=321) against fluorouracil plus cisplatin alone (N=324) in patients with previously untreated, unresectable advanced, recurrent or metastatic esophageal squamous cell carcinoma.The primary endpoints of the trial are overall survival (OS) and progression-free survival (PFS) by blinded independent central review (BICR) in patients with tumor cell PD-L1 expression ≥1% for both Opdivo-based combinations versus chemotherapy. Secondary endpoints of the trial include OS and PFS by BICR in the all-randomized population.In the Opdivo with chemotherapy arm, patients received treatment with Opdivo 240 mg on Day 1 and Day 15, fluorouracil 800 mg/m²/day on Day 1 through Day 5 (for 5 days), and cisplatin 80 mg/m² on Day 1 of four-week cycle. Patients received Opdivo for up to 24 months or until disease progression, unacceptable toxicity or withdrawal of consent, and chemotherapy until disease progression, unacceptable toxicity or withdrawal of consent.In the Opdivo plus Yervoy arm, patients received treatment with Opdivo 3 mg/kg every 2 weeks and Yervoy 1 mg/kg every 6 weeks up to 24 months or until disease progression, unacceptable toxicity or withdrawal of consent.https://news.bms.com/news/corporate-financial/2022/Bristol-Myers-Squibb-Receives-European-Commission-Approval-for-Opdivo-nivolumab-with-Chemotherapy-as-First-Line-Treatment-for-Patients-with/default.aspx
Source: Bristol Myers Squibb
Bristol Myers's Opdivo gets approval for 2 cancer types in EU
Apr. 05, 2022 7:16 AM ET
Bristol-Myers Squibb Company (BMY)
By: Ravikash, SA News Editor2 Comments
The European Commission (EC) approved Bristol Myers Squibb's (NYSE:BMY) drug Opdivo for a type of bladder cancer and a form of esophageal cancer.The EC approved Opdivo (nivolumab) for the adjuvant treatment of adults with muscle-invasive urothelial carcinoma with tumor cell PD-L1 expression ≥1% who are at a high risk of recurrence after undergoing radical resection. https://seekingalpha.com/news/3820670-bristol-myerss-opdivo-gets-approval-for-2-cancer-types-in-eu
https://seekingalpha.com/symbol/BMY
Rubraca® (Rucaparib)
DUPIXENT® (DUPILUMAB)
DUPIXENT® (DUPILUMAB)
Clovis Oncology’s Rubraca® (Rucaparib) Significantly Improves Progression-Free Survival In First-Line Maintenance Treatment In Women With Ovarian Cancer Regardless Of Their Biomarker Status In Phase 3 ATHENA-MONO Trial
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- ATHENA study evaluating Rubraca monotherapy versus placebo (ATHENA-MONO) successfully achieved the primary endpoint of improved PFS in both populations in the primary efficacy analyses: HRD-positive and all patients randomized (ITT)
- Median PFS of 20.2 months for Rubraca vs 9.2 months for placebo in the ITT population
- The exploratory PFS endpoints were also achieved in both HRD-negative and BRCA mutant subgroups of patients
- Safety of Rubraca observed in ATHENA-MONO was consistent with both the current US and European labels
- ATHENA-MONO results will serve as the basis of a supplemental NDA for US label expansion to be submitted during Q2 2022; European submission to follow during Q3 2022
- These data, including additional analyses, have been submitted for presentation at the American Society of Clinical Oncology Annual Meeting in June 2022
BOULDER, Colo.--(BUSINESS WIRE)-- Clovis Oncology, Inc. (NASDAQ: CLVS) today announced positive top-line data from the monotherapy arm of the ATHENA (GOG 3020/ENGOT-ov45) trial (ATHENA-MONO) demonstrating that Rubraca as maintenance treatment successfully achieved the primary endpoint of significantly improved investigator-assessed progression-free survival (PFS) compared with placebo. Benefit was observed in both primary efficacy analyses of newly-diagnosed patients with advanced ovarian cancer following successful treatment with platinum-based chemotherapy: those who had homologous recombination deficiency (HRD-positive)1, including deleterious BRCA mutations, as well as all patients randomized in the trial (overall intent-to-treat population (ITT)). Benefit in PFS was also seen in the exploratory subgroups of patients with HRD-negative2 and BRCA mutant (BRCAm) tumors. The safety of Rubraca observed in the ATHENA-MONO study was consistent with both the US and European labels.Based on these results, the Company plans to submit a supplemental New Drug Application (sNDA) to the US FDA during the second quarter of 2022 followed by a Type II Variation to the EMA during the third quarter of 2022 for a first-line maintenance treatment indication for women with advanced ovarian cancer regardless of biomarker status who have responded to first-line platinum-based chemotherapy.“The results from the ATHENA-MONO study of Rubraca in first-line maintenance treatment ovarian cancer exceeded our expectations in terms of significant improvement in PFS versus placebo in each of the primary efficacy populations, including the all-comers or intent-to-treat population,” said Patrick J. Mahaffy, President and CEO of Clovis Oncology. “We believe that the positive results from ATHENA-MONO demonstrate that Rubraca will provide an important new treatment option for women with advanced ovarian cancer in the first-line maintenance setting, and we look forward to submitting these data to the regulatory authorities in the US and Europe during Q2 and Q3 2022, respectively. Most importantly, I would like to thank the patients, physicians, and our colleagues whose commitment to this trial made these results possible, which now offer the potential to make a difference in the lives of many women with advanced ovarian cancer. We would also like to thank GOG and ENGOT for their partnership in conducting this large and very important trial.”“While PARP inhibitors have shown efficacy as first-line maintenance treatment for patients with advanced ovarian cancer, questions still remain about the patient population that may benefit from their use. The results of ATHENA-MONO address many of these unanswered questions and expands the opportunity for rucaparib in all patients regardless of biomarker status,” said Bradley J. Monk, MD, FACOG, FACS, at GOG Foundation, HonorHealth Research Institute, University of Arizona College of Medicine, Creighton University School of Medicine, Phoenix, AZ and global primary investigator of the ATHENA trial.“I believe the significant improvement in PFS demonstrated in the ATHENA-MONO trial underscores the importance of first-line maintenance therapy and the benefit that rucaparib can provide to women with advanced ovarian cancer irrespective of HRD status,” said Rebecca S. Kristeleit, MD, PhD, of Guy’s and St Thomas’ NHS Foundation Trust in London and lead ENGOT/NCRI National Cancer Research Institute (https://www.ncri.org.uk/) investigator of the ATHENA trial. “Ovarian cancer remains a leading cause of cancer-related death among women, which highlights the continued need for new treatment options and strategies for women with newly-diagnosed disease. The ATHENA-MONO study demonstrates the role of rucaparib monotherapy in the first-line maintenance treatment setting for advanced ovarian cancer.”ATHENA is a double-blind, placebo-controlled, Phase 3 trial of rucaparib in first-line ovarian cancer maintenance treatment. It has two parts which are statistically independent. The top-line results reported today are from the ATHENA-MONO part (rucaparib vs placebo) with results from the ATHENA-COMBO part (rucaparib+nivolumab vs rucaparib) now expected in Q1 2023 based on a slower than expected event count.ATHENA-MONO enrolled 538 women with high-grade ovarian, fallopian tube, or primary peritoneal cancer. The primary efficacy analysis evaluated two prospectively defined molecular sub-groups in a step-down manner: 1) HRD-positive (inclusive of BRCAm tumors), and 2) all patients randomized (ITT) in ATHENA-MONO.Following is a summary of the primary efficacy analyses by investigator review, the primary analysis of ATHENA-MONO.
Significant Improvement in PFS in the HRD-positive Patient Population
By investigator review, the rucaparib arm (n=185) successfully achieved statistical significance over the placebo arm (n=49) for the primary endpoint of PFS with a hazard ratio of 0.47 (95% CI: 0.31-0.72). The median PFS for the HRD-positive patient population treated with rucaparib was 28.7 months vs 11.3 months among those who received placebo (p=0.0004).
Significant Improvement in PFS in All Patients Studied (ITT or all comers)
Rucaparib also showed statistical significance in all 538 patients randomized in the ATHENA-MONO comparison. By investigator review, the rucaparib arm (n=427) successfully achieved statistical significance over the placebo arm (n=111) for the primary endpoint of PFS with a hazard ratio of 0.52 (95% CI: 0.40-0.68). The median PFS for all patients enrolled in ATHENA-MONO and treated with rucaparib was 20.2 months vs 9.2 months among those who received placebo (p<0.0001).
Treatment Benefit in PFS Endpoint for Exploratory HRD-negative Subgroup
By investigator review, the PFS endpoint in the exploratory subgroup of HRD-negative demonstrated a hazard ratio of 0.65 (95% CI: 0.45-0.95). The median PFS for these patients treated with rucaparib (n=189) was 12.1 months vs. 9.1 months for those who received placebo (n=49) (p=0.0284).
Treatment Benefit in PFS Endpoint for Exploratory BRCAm Subgroup
By investigator review, the PFS endpoint in the exploratory subgroup of BRCAm demonstrated a hazard ratio of 0.40 (95% CI: 0.21-0.75). The median PFS for these patients treated with rucaparib (n=91) was Not Reached vs 14.7 months for those who received placebo (n=24) (p=0.0041).Results were consistent for the germline BRCA (n=68) and somatic BRCA (n=33) and unknown (n=14) populations.
Summary of ATHENA-MONO Safety
The safety of Rubraca observed in ATHENA-MONO was consistent with both the current US and European labels. The most common (≥5%) treatment-emergent grade 3/4 adverse events (TEAEs) among all patients treated with rucaparib in the monotherapy portion of the ATHENA study were anemia/decreased hemoglobin (28.7%), neutropenia (14.6%), ALT/AST increase (10.6%), and thrombocytopenia (7.1%). The discontinuation rate for TEAEs was 11.8% for rucaparib-treated patients and 5.5% for the placebo arm. The rate of treatment-emergent myelodysplastic syndrome (MDS)/acute myeloid leukemia (AML) in the rucaparib arm was 0.2%, and no patients on the placebo arm experienced treatment-emergent MDS/AML.Clovis Oncology plans to provide an expanded description of the ATHENA-MONO results in a scientific session at a medical meeting later this year; these data have been submitted for presentation at the American Society of Clinical Oncology Annual Meeting in June 2022.Rubraca is not currently approved in the first-line ovarian cancer maintenance setting. Clovis intends to provide these data to US and European regulatory authorities and is on track to submit filings during the second and third quarters of 2022, respectively, in those geographies.
About the ATHENA Clinical Trial
ATHENA (GOG 3020/ENGOT-ov45) (NCT03522246) is an international, randomized, double-blind, phase III trial consisting of two separate and fully independently powered study comparisons evaluating Rubraca monotherapy (ATHENA-MONO) and Rubraca in combination with nivolumab (ATHENA-COMBO) as maintenance treatment for patients with newly diagnosed advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer. ATHENA enrolled approximately 1000 patients across 24 countries, all women with newly diagnosed ovarian cancer who responded to their first-line chemotherapy. The trial completed accrual in 2020 and was conducted in association with the Gynecologic Oncology Group (GOG) in the US and the European Network of Gynaecological Oncological Trial groups (ENGOT) in Europe. GOG and ENGOT are the two largest cooperative groups in the US and Europe dedicated to the treatment of gynecological cancers.ATHENA-MONO is evaluating the benefit of Rubraca monotherapy versus placebo in 538 women in this patient population. The primary efficacy analysis evaluated two prospectively defined molecular sub-groups in a step-down manner: 1) HRD-positive (inclusive of BRCA mutant) tumors, and 2) the intent-to-treat population, or all patients treated in ATHENA-MONO.The ATHENA-COMBO portion of the trial, anticipated to readout in Q1 2023, is evaluating the magnitude of benefit of adding Opdivo (nivolumab) to Rubraca monotherapy in the ovarian cancer first-line maintenance treatment setting. ATHENA-COMBO is anticipated to be the first Phase 3 dataset to readout evaluating the combination of a PARP inhibitor and an immune checkpoint inhibitor as maintenance treatment following completion and response to front-line chemotherapy.
About Rubraca (rucaparib)
Rucaparib is an oral, small molecule inhibitor of PARP1, PARP2 and PARP3 being developed in multiple tumor types, including ovarian and metastatic castration-resistant prostate cancers, as monotherapy, and in combination with other anti-cancer agents. Exploratory studies in other tumor types are also underway.Rubraca is an unlicensed medical product outside of the US and Europe.
Rubraca Ovarian Cancer US FDA Approved Indications
Rubraca is indicated for the maintenance treatment of adult women with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in a complete or partial response to platinum-based chemotherapy.Rubraca is indicated for the treatment of adult women with a deleterious BRCA mutation (germline and/or somatic)-associated epithelial ovarian, fallopian tube, or primary peritoneal cancer who have been treated with two or more chemotherapies. Select patients for therapy based on an FDA-approved companion diagnostic for Rubraca.https://www.rubraca.com/
Clovis Oncology is headquartered in Boulder, Colorado, with additional office locations in the US and Europe. Please visit www.clovisoncology.com for more information.
Source: Clovis Oncology, Inc. View source version on businesswire.com: https://www.businesswire.com/news/home/20220331005384/en/
Clovis Oncology extends two-day rally after trial win for ovarian cancer therapy
Apr. 04, 2022 3:59 PM ET
By: Dulan Lokuwithana, SA News Editor
- The commercial-stage biotech Clovis Oncology (CLVS +9.0%) continues to trade higher on Monday extending the recent rally to third consecutive session following the positive late-stage results announced by the company last week for Rubraca in ovarian cancer.
- The announcement that the monotherapy arm of the Phase 3 ATHENA trial met the primary endpoint for Rubraca as maintenance treatment propelled beaten-down Clovis (NASDAQ:CLVS) shares last week.
- https://seekingalpha.com/news/3820519-clovis-oncology-extends-two-day-rally-after-trial-win-for-ovarian-cancer-therapy
- https://seekingalpha.com/symbol/CLVS
- https://www.rubraca.com/
DUPIXENT® (DUPILUMAB)
Yescarta® (axicabtagene ciloleucel)
DUPIXENT® (DUPILUMAB)
FDA ACCEPTS DUPIXENT® (DUPILUMAB) FOR PRIORITY REVIEW IN PATIENTS AGED 12 YEARS AND OLDER WITH EOSINOPHILIC ESOPHAGITIS
If approved, Dupixent would be the first medicine available in the U.S. indicated to treat eosinophilic esophagitisThere are approximately 160,000 patients in the U.S. living with eosinophilic esophagitis who are currently treated, of whom approximately 48,000 have failed multiple treatments
TARRYTOWN, N.Y. and PARIS, April 4, 2022 /PRNewswire/ -- Regeneron Pharmaceuticals, Inc. (NASDAQ: REGN) and Sanofi today announced the U.S. Food and Drug Administration (FDA) has accepted for Priority Review the supplemental Biologics License Application (sBLA) for Dupixent® (dupilumab) 300 mg weekly to treat adult and pediatric patients aged 12 years and older with eosinophilic esophagitis (EoE), a chronic and progressive type 2 inflammatory disease that damages the esophagus and impairs the ability to swallow. The target action date for the FDA decision on this investigational use is August 3, 2022.The sBLA is supported by data from two Phase 3 trials evaluating the efficacy and safety of Dupixent 300 mg weekly in patients aged 12 years and older with EoE (Part A and Part B), and data from an active long-term extension trial. Dupixent 300 mg weekly significantly improved the signs and symptoms of EoE at 24 weeks compared to placebo, including the ability to swallow and reduction in eosinophil count in the esophagus. The safety results of these trials were generally consistent with the known safety profile of Dupixent in its approved indications. The most common adverse event observed with Dupixent, in Part A and Part B, was injection site reactions.In September 2020, the U.S. FDA granted Breakthrough Therapy designation to Dupixent for the treatment of patients aged 12 years and older with EoE. Dupixent was also granted Orphan Drug designation for the potential treatment of EoE in 2017. Priority review is granted to therapies that have the potential to provide significant improvements in the treatment, diagnosis or prevention of serious conditions. Regulatory filings around the world are also planned in 2022. The potential use of Dupixent in EoE is currently under clinical development, and the safety and efficacy have not been fully evaluated by any regulatory authority.
About Eosinophilic Esophagitis (EoE)
EoE is a chronic, progressive type 2 inflammatory disease that damages the esophagus and prevents it from working properly. For people with EoE, swallowing the smallest amount of food can be a painful and worrisome choking experience. Those with EoE live with anxiety and frustration from having a constantly evolving list of foods to avoid. This disease can also cause narrowing of the esophagus and dilation (physical expansion) of the esophagus may be needed, which is often painful. In severe cases, a feeding tube is the only option to ensure proper caloric intake and adequate nutrition. People with EoE may have poor quality of life and are more likely to experience depression than people without EoE. There are approximately 160,000 patients in the U.S. living with EoE who are currently treated, of whom approximately 48,000 have failed multiple treatments.
About Dupixent
Dupixent, which was invented using Regeneron's proprietary VelocImmune® technology, is a fully human monoclonal antibody that inhibits the signaling of the interleukin-4 (IL-4) and interleukin-13 (IL-13) pathways and is not an immunosuppressant. By demonstrating significant clinical benefit together with a decrease in type 2 inflammation following IL-4 and IL-13 blockade with Dupixent, the Dupixent Phase 3 clinical program has established that IL-4 and IL-13 are key drivers of the type 2 inflammation that plays a major role in multiple related and often co-morbid diseases for which Dupixent is approved including atopic dermatitis, asthma and chronic rhinosinusitis with nasal polyposis (CRSwNP), as well as investigational diseases such as EoE and prurigo nodularis, which have been studied in Phase 3 trials.In the U.S., Dupixent is approved in patients aged 6 years and older with uncontrolled moderate-to-severe atopic dermatitis; as an add-on maintenance treatment of patients aged 6 years and older with moderate-to-severe asthma characterized by an eosinophilic phenotype or with oral corticosteroid-dependent asthma; and for use with other medicines for the maintenance treatment of chronic rhinosinusitis with nasal polyposis (CRSwNP) in adults whose disease is not controlled.Dupixent is also approved in Europe, Japan and other countries around the world for use in specific patients with moderate-to-severe atopic dermatitis and certain patients with asthma or CRSwNP in different age populations. Dupixent is approved in one or more of these indications in more than 60 countries around the world, and more than 400,000 patients have been treated globally.https://www.dupixent.com/
U.S. IndicationsDUPIXENT is a prescription medicine used:
- to treat adults and children 6 years of age and older with moderate-to-severe atopic dermatitis (eczema) that is not well controlled with prescription therapies used on the skin (topical), or who cannot use topical therapies. DUPIXENT can be used with or without topical corticosteroids. It is not known if DUPIXENT is safe and effective in children with atopic dermatitis under 6 years of age.
- with other asthma medicines for the maintenance treatment of moderate-to-severe eosinophilic or oral steroid dependent asthma in adults and children 6 years of age and older whose asthma is not controlled with their current asthma medicines. DUPIXENT helps prevent severe asthma attacks (exacerbations) and can improve your breathing. DUPIXENT may also help reduce the amount of oral corticosteroids you need while preventing severe asthma attacks and improving your breathing. DUPIXENT is not used to treat sudden breathing problems. It is not known if DUPIXENT is safe and effective in children with asthma under 6 years of age.
- with other medicines for the maintenance treatment of chronic rhinosinusitis with nasal polyposis (CRSwNP) in adults whose disease is not controlled. It is not known if DUPIXENT is safe and effective in children with chronic rhinosinusitis with nasal polyposis under 18 years of age.
Please see accompanying full Prescribing Information including Patient Information.
For additional information about the company, please visit www.regeneron.com or follow @Regeneron on Twitter.
Sanofi is listed on EURONEXT: SAN and NASDAQ: SNY. View original content:https://www.prnewswire.com/news-releases/fda-accepts-dupixent-dupilumab-for-priority-review-in-patients-aged-12-years-and-older-with-eosinophilic-esophagitis-301516398.htmlSOURCE Regeneron Pharmaceuticals, Inc.
Sanofi, Regeneron's Dupixent gets FDA priority review for eosinophilic esophagitis
Apr. 04, 2022 6:01 AM ET
By: Ravikash, SA News Editor
- Regeneron Pharmaceuticals (NASDAQ:REGN) and Sanofi (NASDAQ:SNY) said the U.S. Food and Drug Administration (FDA) granted priority review to Dupixent to treat patients aged 12 years and older with eosinophilic esophagitis (EoE).
- https://seekingalpha.com/news/3820235-sanofi-regenerons-dupixent-gets-fda-priority-review-for-eosinophilic-esophagitis
- https://seekingalpha.com/symbol/SNY
- https://seekingalpha.com/symbol/REGN
- https://www.dupixent.com/
- https://www.regeneron.com/
Yescarta® (axicabtagene ciloleucel)
Yescarta® (axicabtagene ciloleucel)
Yescarta® (axicabtagene ciloleucel)
April 01, 2022
Yescarta® Receives U.S. FDA Approval as First CAR T-cell Therapy for Initial Treatment of Relapsed or Refractory Large B-cell Lymphoma (LBCL)
-- First LBCL Treatment to Improve Upon Standard of Care in Nearly 30 Years ---- Landmark ZUMA-7 Study Demonstrated Patients on Yescarta Were 2.5 Times More Likely to Be Alive at Two Years Without Cancer Progression or Need for Additional Cancer Treatment ---- Yescarta is First CAR T-cell Therapy to Receive NCCN Treatment Guideline Category 1 Recommendation -
-SANTA MONICA, Calif.--(BUSINESS WIRE)-- Kite, a Gilead Company (Nasdaq: GILD), today announced the U.S. Food and Drug Administration (FDA) has approved Yescarta® (axicabtagene ciloleucel) CAR T-cell therapy for adult patients with large B-cell lymphoma that is refractory to first-line chemoimmunotherapy or that relapses within 12 months of first-line chemoimmunotherapy. Yescarta demonstrated a clinically meaningful and statistically significant improvement in event-free survival (EFS; hazard ratio 0.398; P< 0.0001) over the current standard of care (SOC) that has been in place for decades. EFS was determined by blinded central review and defined as the time from randomization to the earliest date of disease progression, commencement of new lymphoma therapy, or death from any cause. Additionally, 2.5 times more patients receiving Yescarta (40.5%) were alive at two years without disease progression or need for additional cancer treatment, after their one-time infusion of Yescarta vs. SOC (16.3%), and the median EFS was four-fold greater (8.3 months vs. 2.0 months) with Yescarta vs. SOC. Yescarta is also being reviewed by global regulatory authorities for additional indications inclusive of the ZUMA-7 patient population. ZUMA-7 is considered a landmark trial for being the first and largest trial of its kind, with the longest follow-up.This press release features multimedia. View the full release here: https://www.businesswire.com/news/home/20220401005519/en/Earlier this month, the National Comprehensive Cancer Network (NCCN) updated its Clinical Practice Guidelines in Oncology for B-cell Lymphomas to include Yescarta for “Relapsed disease <12 mo or Primary Refractory disease” under Diffuse Large B-cell Lymphoma (DLBCL) as a Category 1 recommendation. Yescarta is the first CAR T-cell therapy to receive a NCCN Category 1 recommendation. NCCN defines Category 1 as recommendations based upon high-level evidence with uniform NCCN consensus that the intervention is appropriate.
About ZUMA-7 Study
The FDA approval of Yescarta CAR T-cell therapy for adult patients with large B-cell lymphoma (LBCL) that is refractory to first-line chemoimmunotherapy or that relapses within 12 months of first-line chemoimmunotherapy is based on results from the ZUMA-7 study. Patients had not yet received treatment for relapsed or refractory lymphoma and were potential candidates for autologous stem cell transplant (ASCT). Results were presented in a Plenary session at the American Society of Hematology’s (ASH) Annual Meeting & Exposition in December 2021 and simultaneously published in the NewEngland Journal of Medicine (NEJM).ZUMA-7 is a randomized, open-label, global, multicenter, Phase 3 study evaluating the safety and efficacy of Yescarta versus current standard of care (SOC) for second-line therapy (platinum-based salvage combination chemoimmunotherapy regimen followed by high-dose therapy [HDT] and ASCT in those who respond to salvage chemotherapy) in adult patients with relapsed or refractory LBCL within 12 months of first-line therapy. In the study, 359 patients in 77 centers around the world were randomized (1:1) to receive a single infusion of Yescarta or current SOC second-line therapy. The primary endpoint is event-free survival (EFS) as determined by blinded central review and defined as the time from randomization to the earliest date of disease progression per Lugano Classification, commencement of new lymphoma therapy, or death from any cause. Key secondary endpoints include objective response rate (ORR) and overall survival (OS). Additional secondary endpoints include patient reported outcomes (PROs) and safety.Yescarta demonstrated a 2.5-fold increase in patients who were alive at two years and did not experience cancer progression or require the need for additional cancer treatment (40.5% vs. 16.3%) and a four-fold greater median EFS (8.3 mo. vs. 2.0 mo.) compared to SOC (hazard ratio 0.398; 95% CI: 0.308-0.514, P<0.0001). In addition to being the largest and longest study of its kind, ZUMA-7 study participants on the Yescarta arm did not receive additional bridging chemotherapy that could have potentially confounded results.Nearly three times as many patients randomized to Yescarta ultimately received the definitive CAR T-cell therapy treatment (94%) versus those randomized to SOC (35%) who received on-protocol HDT+ASCT. More patients responded to Yescarta (ORR: 83% vs. 50%, odds ratio: 5.31 [95% CI: 3.1-8.9; P<0.0001) and achieved a complete response (CR) with Yescarta (CR rate: 65% vs. 32%) than with SOC. At a pre-specified interim analysis at the time of the primary EFS analysis, OS has not met the criteria for statistical significance, but favored Yescarta.Fifty-five percent of patients in the SOC arm subsequently received CD19-directed CAR T-cell therapy off study.In the study, Yescarta had a safety profile that was consistent with previous studies. Among the 168 Yescarta-treated patients evaluable for safety, Grade ≥3 cytokine release syndrome (CRS) and neurologic events were observed in 7% and 25% of patients, respectively. In the SOC arm, 83% of patients had high grade events, mostly cytopenias (low blood counts).The Yescarta U.S. Prescribing Information has a BOXED WARNING for the risks of CRS and neurologic toxicities, and Yescarta is approved with a Risk Evaluation and Mitigation Strategy (REMS) due to these risks; see below for Important Safety Information.
About LBCL
Globally, LBCL is the most common type of non-Hodgkin lymphoma (NHL). In the United States, more than 18,000 people are diagnosed with LBCL each year. About 30-40% of patients with LBCL will need second-line treatment, as their cancer will either relapse (return) or become refractory (not respond) to initial treatment.
About Yescarta
Please see full Prescribing Information, including BOXED WARNING and Medication Guide.YESCARTA is a CD19-directed genetically modified autologous T cell immunotherapy indicated for the treatment of:
- Adult patients with large B-cell lymphoma that is refractory to first-line chemoimmunotherapy or that relapses within 12 months of first-line chemoimmunotherapy.
- Adult patients with relapsed or refractory large B-cell lymphoma after two or more lines of systemic therapy, including diffuse large B-cell lymphoma (DLBCL) not otherwise specified, primary mediastinal large B-cell lymphoma, high grade B-cell lymphoma, and DLBCL arising from follicular lymphoma.
Limitations of Use: YESCARTA is not indicated for the treatment of patients with primary central nervous system lymphoma.
- Adult patients with relapsed or refractory follicular lymphoma (FL) after two or more lines of systemic therapy. This indication is approved under accelerated approval based on response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trial(s).
- https://www.yescarta.com/
Further information is available at www.YescartaTecartusREMS.com or 1-844-454-KITE (5483).
For more information on Kite, please visit www.kitepharma.com.
U.S. Prescribing Information for Yescarta including BOXED WARNING, is available at www.kitepharma.com and www.gilead.com.Kite, the Kite logo, Yescarta, Tecartus, XLP and GILEAD are trademarks of Gilead Sciences, Inc. or its related companies.For more information on Kite, please visit the company’s website at www.kitepharma.com. Follow Kite on social media on Twitter (@KitePharma) and LinkedIn.View source version on businesswire.com: https://www.businesswire.com/news/home/20220401005519/en/ Source: Gilead Sciences, Inc.
Gilead granted FDA label expansion for Yescarta in B-cell lymphoma
Apr. 01, 2022 6:30 PM ET
By: Dulan Lokuwithana, SA News Editor7 Comments
- The U.S. Food and Drug Administration (FDA) has approved the CAR T-cell therapy Yescarta as an initial treatment for adult patients with relapsed or refractory large B-cell lymphoma (LBCL), Kite, a unit of Gilead (NASDAQ:GILD) announced on Friday.
- https://seekingalpha.com/news/3820134-gilead-granted-fda-label-expansion-for-yescarta-in-b-cell-lymphoma
- https://seekingalpha.com/symbol/GILD
- https://www.gilead.com/
Retevmo® (selpercatinib)
Yescarta® (axicabtagene ciloleucel)
Yescarta® (axicabtagene ciloleucel)
Lilly Presents Updated Data on Retevmo® (selpercatinib) in Advanced RET Fusion-Positive Non-Small-Cell Lung Cancer (NSCLC) at the 2022 European Lung Cancer Congress
April 1, 2022Download PDFINDIANAPOLIS, April 1, 2022 /PRNewswire/ -- Eli Lilly and Company (NYSE: LLY) today announced updated data from the Phase 1/2 LIBRETTO-001 trial of Retevmo® (selpercatinib 40 mg & 80 mg capsules) in patients with RET fusion-positive non-small cell lung cancer (NSCLC). Retevmo (marketed as Retsevmo® outside of the U.S.) is a selective and potent RET kinase inhibitor that is approved in multiple countries including the United States for treatment of adult patients with metastatic rearranged during transfection (RET) fusion-positive NSCLC, and the treatment of adult and pediatric patients 12 years of age and older with advanced or metastatic RET-mutant medullary thyroid cancer (MTC) who require systemic therapy, or advanced or metastatic RET fusion-positive thyroid cancer who require systemic therapy and who are radioactive iodine-refractory (if radioactive iodine is appropriate). These data were presented at the European Lung Cancer (ELCC) 2022 (poster 27p)."The LIBRETTO trial provides the largest set of clinical data for a RET inhibitor and these results continue to demonstrate evidence of meaningful clinical outcomes for patients with metastatic RET fusion-positive NSCLC treated with Retevmo, including those with difficult-to-treat brain metastases," said David Hyman, M.D. chief medical officer, oncology at Lilly. "We are continuing to build on the robust body of evidence supporting Retevmo, including through an ongoing randomized Phase 3 confirmatory study, with a planned readout in 2023."The updated analysis utilized a June 15, 2021, data cut-off and included 355 patients who were eligible for efficacy analysis, 247 of which were previously treated with at least one line of platinum chemotherapy and 69 of which were treatment-naïve. Patients who were previously treated with at least one line of platinum chemotherapy received a median of two prior treatment regimens (range: 1-15), with 58% having received anti-PD-1 or anti-PD-L1 therapy. Responses are based on independent review committee (IRC) assessment.Among 247 patients previously treated with platinum chemotherapy, the confirmed objective response rate (ORR) was 61.1% (95% CI: 54.7-67.2%) and among 69 treatment-naïve patients, the confirmed ORR was 84.1% (95% CI: 73.3-91.8%). Twenty-six patients had measurable central nervous system (CNS) metastases at baseline and treatment with Retevmo resulted in a CNS ORR of 84.6%, with 22 patients having a confirmed best response of complete response or partial response. At a median follow-up of approximately two years in both the treatment-naïve and platinum-chemotherapy pretreated populations, median duration of response (DoR) is estimated at 20.2 (55.2% censoring rate; 20.3 months median duration of follow-up) and 28.6 (60.9% censoring rate; 21.2 months median duration of follow-up) months, respectively and median progression free survival (PFS) is estimated at 22.0 (53.6% censoring rate; 21.9 months median duration of follow-up) and 24.9 (55.9% censoring rate; 24.7 months median duration of follow-up) months, respectively. Of the 26 patients with measurable CNS disease, Retevmo treatment resulted in a median intracranial PFS of 19.4 months. These median estimates remain immature.Safety among patients in this cohort was consistent with the known safety profile of Retevmo. In the safety population (all NSCLC patients that received at least one dose of Retevmo, N=356), the most common adverse events (AEs in ≥25% of patients) were dry mouth, diarrhea, hypertension, increased ALT/AST, peripheral edema, constipation, rash, headache, and fatigue. Thirty-four patients discontinued due to an adverse event (10%), eleven (3%) of which were deemed related to Retevmo.A global, randomized, Phase 3 trial is currently recruiting and will compare treatment with Retevmo to the current standard of care in the first-line treatment of advanced or metastatic RET fusion-positive NSCLC.Retevmo was the first RET inhibitor to receive Accelerated Approval from the U.S. Food and Drug Administration (FDA) in May 2020 and was the first approved by the European Commission in February 2021. Retevmo was approved under the FDA's Accelerated Approval regulations based on the LIBRETTO-001 Phase 1/2 trial's endpoints of objective response rate and duration of response. Continued approval for these indications may be contingent upon verification and description of clinical benefit in confirmatory trials.
About LIBRETTO-001The Phase 1/2 LIBRETTO-001 trial is the largest clinical trial of patients with RET-driven cancers treated with a RET inhibitor. The trial, which spans 16 countries and 89 sites, included a dose escalation phase (Phase 1) and a dose expansion phase (Phase 2). The primary objective was to determine ORR by independent review committee (IRC) and key secondary objectives included DoR, CNS ORR & DOR, safety and PFS.LIBRETTO-001 continues to enroll patients with RET-altered tumors beyond lung cancer.
About Retevmo® (selpercatinib)Retevmo (selpercatinib, formerly known as LOXO-292) (pronounced ret- tév-mo) is a selective and potent RET kinase inhibitor. Retevmo may affect both tumor cells and healthy cells, which can result in side effects. RET-driver alterations are predominantly mutually exclusive from other oncogenic drivers. Retevmo is an U.S. FDA-approved oral prescription medicine, 120 mg or 160 mg dependent on weight (<50 kg or ≥50 kg, respectively), taken twice daily until disease progression or unacceptable toxicity. Continued approval may be contingent upon verification and description of clinical benefit in confirmatory trials.https://www.retevmo.com/
Please see full Prescribing Information for Retevmo.
To learn more, visit Lilly.com and Lilly.com/newsroom or follow us on Facebook, Instagram, Twitter and LinkedIn. P-LLY View original content to download multimedia:https://www.prnewswire.com/news-releases/lilly-presents-updated-data-on-retevmo-selpercatinib-in-advanced-ret-fusion-positive-non-small-cell-lung-cancer-nsclc-at-the-2022-european-lung-cancer-congress-301515462.htmlSOURCE Eli Lilly and Company
Lilly reports new data from phase 1/2 trial of Retevmo in advanced lung cancer
Apr. 01, 2022 8:01 AM ET Eli Lilly and Company (LLY)
By: Ravikash, SA News Editor Eli Lilly (NYSE:LLY)
reported updated data from a phase 1/2 trial of Retevmo (selpercatinib 40 mg & 80 mg capsules) in patients with RET fusion-positive non-small cell lung cancer (NSCLC).https://seekingalpha.com/news/3819786-lilly-reports-new-data-from-phase-12-trial-of-retevmo-in-advanced-lung-cancerhttps://seekingalpha.com/symbol/LLYhttps://www.retevmo.com/https://www.lilly.com/
BIOTECNOVA™
CABOMETYX® (cabozantinib)
CABOMETYX® (cabozantinib)
CABOMETYX® (cabozantinib)
Exelixis’ Partner Ipsen Receives Positive CHMP Opinion for CABOMETYX® (cabozantinib) for Patients with Previously Treated Radioactive Iodine-Refractory Differentiated Thyroid CancerPDF Version
– CHMP recommendation follows September 2021 U.S. FDA approval of CABOMETYX in this setting –
ALAMEDA, Calif.--(BUSINESS WIRE)--Mar. 25, 2022-- Exelixis, Inc. (Nasdaq: EXEL) today announced that its partner Ipsen received a positive opinion from the Committee for Medicinal Products for Human Use (CHMP), the scientific committee of the European Medicines Agency (EMA), for CABOMETYX® (cabozantinib) as a monotherapy for the treatment of adult patients with locally advanced or metastatic differentiated thyroid carcinoma (DTC), refractory or not eligible to radioactive iodine (RAI) who have progressed during or after prior systemic therapy. The European Commission, which has the authority to approve medicines for the European Union, will now review the CHMP recommendation, and a final decision on the application is expected in the coming months.
“The CHMP’s recommendation is an important milestone for our partner Ipsen in their efforts to bring CABOMETYX to patients in Europe with radioactive iodine-refractory differentiated thyroid cancer that has progressed following prior systemic therapy,” said Vicki L. Goodman, M.D., Executive Vice President, Product Development & Medical Affairs, and Chief Medical Officer at Exelixis. “These patients have a poor prognosis, and there are currently no standard treatment options approved in Europe following progression on anti-VEGFR therapy. We look forward to hearing the European Commission’s decision in the coming months, with the hope that a new therapy will soon be available to these patients and their caregivers.”
The CHMP recommendation is based on results from COSMIC-311, the phase 3 pivotal trial that demonstrated significant improvement in progression-free survival (PFS) with CABOMETYX versus placebo in patients with RAI-refractory DTC who progressed after up to two prior VEGFR-targeted therapies. COSMIC-311 was the basis for the U.S. Food and Drug Administration (FDA) approval of CABOMETYX in September 2021 for the treatment of adult and pediatric patients 12 years of age and older with locally advanced or metastatic DTC that has progressed following VEGFR-targeted therapy and who are RAI-refractory or ineligible. CABOMETYX is currently approved in the European Union as a monotherapy for the treatment of advanced renal cell carcinoma (RCC) in adults who have received prior VEGF-targeted therapy, for previously untreated intermediate- or poor-risk advanced RCC and for hepatocellular carcinoma (HCC) in adults who have been previously treated with sorafenib. CABOMETYX in combination with OPDIVO® (nivolumab) is approved as a first-line treatment for advanced RCC.
About COSMIC-311
COSMIC-311 was a multicenter, randomized, double-blind, placebo-controlled phase 3 pivotal trial that enrolled 258 patients at 164 sites globally. Patients were randomized in a 2:1 ratio to receive either CABOMETYX 60 mg or placebo once daily. The primary endpoints were PFS and objective response rate. Exelixis is sponsoring COSMIC-311, and Ipsen is co-funding the trial. More information about this trial is available at ClinicalTrials.gov.
About CABOMETYX® (cabozantinib)
In the U.S., CABOMETYX tablets are approved for the treatment of patients with advanced RCC; for the treatment of patients with HCC who have been previously treated with sorafenib; for patients with advanced RCC as a first-line treatment in combination with nivolumab; and for adult and pediatric patients 12 years of age and older with locally advanced or metastatic DTC that has progressed following prior VEGFR-targeted therapy and who are RAI-refractory or ineligible. CABOMETYX tablets have also received regulatory approvals in the European Union and additional countries and regions worldwide. In 2016, Exelixis granted Ipsen exclusive rights for the commercialization and further clinical development of cabozantinib outside of the U.S. and Japan. Under the terms of the license agreement with Ipsen, Exelixis is eligible to receive development, regulatory and sales milestone payments from Ipsen and further receive royalties on net sales of cabozantinib by Ipsen outside of the U.S. and Japan. In 2017, Exelixis granted exclusive rights to Takeda Pharmaceutical Company Limited for the commercialization and further clinical development of cabozantinib for all future indications in Japan. Exelixis holds the exclusive rights to develop and commercialize cabozantinib in the U.S.
Please see accompanying full Prescribing Information https://www.cabometyx.com/downloads/CABOMETYXUSPI.pdf.
For more information about Exelixis, please visit www.exelixis.com, follow @ExelixisInc on Twitter or like Exelixis, Inc. on Facebook.
Exelixis, the Exelixis logo, CABOMETYX and COMETRIQ are registered U.S. trademarks of Exelixis.
COTELLIC is a registered trademark of Genentech, Inc.
MINNEBRO is a registered trademark of Daiichi Sankyo Company, Limited.
OPDIVO® is a registered trademark of Bristol-Myers Squibb Company.
View source version on businesswire.com: https://www.businesswire.com/news/home/20220323005988/en/
Source: Exelixis, Inc.
Ipsen, Exelixis' Cabometyx gets EMA panel nod for expanded use in thyroid cancer
Mar. 25, 2022 9:30 AM ET
Ipsen S.A. (IPSEY), IPSEF, EXEL
By: Ravikash, SA News Editor2 Comments
- A committee of the European Medicines Agency (EMA) recommended the approval of expanded use of Ipsen (OTCPK:IPSEF) (OTCPK:IPSEY) and Exelixis' (NASDAQ:EXEL) Cabometyx as a standalone therapy for certain patients with differentiated thyroid cancer (DTC).
- https://seekingalpha.com/news/3817472-ipsen-exelixis-cabometyx-gets-ema-panel-nod-for-expanded-use-thyroid-cancer
- https://seekingalpha.com/symbol/IPSEY
- https://seekingalpha.com/symbol/IPSEF
- https://seekingalpha.com/symbol/EXEL
- https://www.cabometyx.com/
MARCH 25, 2022
Ipsen receives positive CHMP opinion for Cabometyx® in radioactive iodine-refractory differentiated thyroid cancer
- Recommendation based on data from the COSMIC-311 Phase III trial, in which Cabometyx® (cabozantinib) demonstrated a 78% reduction in risk of disease progression or death versus placebo1
PARIS, FRANCE, 25 March 2022 – Ipsen (Euronext: IPN; ADR: IPSEY)
KEYTRUDA® (pembrolizumab)
CABOMETYX® (cabozantinib)
CABOMETYX® (cabozantinib)
Merck Receives Positive EU CHMP Opinion for KEYTRUDA® (pembrolizumab) for Patients With Microsatellite Instability-High (MSI-H) or Mismatch Repair Deficient (dMMR) Tumors in Five Different Types of Cancer
March 25, 2022 9:00 am ETRecommendation Supports Use of KEYTRUDA for Certain Patients With Unresectable or Metastatic MSI-H/dMMR Colorectal, Gastric, Small Intestine or Biliary Cancer, as Well as Advanced or Recurrent MSI-H/dMMR Endometrial CarcinomaKENILWORTH, N.J.--(BUSINESS WIRE)-- Merck (NYSE: MRK), known as MSD outside the United States and Canada, today announced the European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has adopted a positive opinion recommending approval of KEYTRUDA, Merck’s anti-PD-1 therapy, as monotherapy for the treatment of the following microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) tumors in adults with: unresectable or metastatic colorectal cancer after previous fluoropyrimidine-based combination therapy; advanced or recurrent endometrial carcinoma who have disease progression on or following prior treatment with a platinum-containing therapy in any setting and who are not candidates for curative surgery or radiation; unresectable or metastatic gastric, small intestine or biliary cancer who have disease progression on or following at least one prior therapy.“We are committed to advancing the use of biomarkers to identify patients most likely to respond to KEYTRUDA,” said Dr. Scot Ebbinghaus, vice president, global clinical development, Merck Research Laboratories. “This positive CHMP opinion reinforces the predictive value of MSI-H/dMMR across many different cancer types and the importance of biomarker testing. KEYTRUDA has already become an important first-line treatment option for certain patients in Europe with MSI-H or dMMR colorectal cancer, and we are pleased the CHMP has recommended KEYTRUDA as a monotherapy for additional patients with MSI-H or dMMR tumors.”The CHMP’s recommendation was based on results from the Phase 2 KEYNOTE-158 trial as well as results from the Phase 2 KEYNOTE-164 trial, both of which also supported the U.S. Food and Drug Administration’s accelerated approval of KEYTRUDA as the first cancer treatment approved based on a biomarker in MSI-H or dMMR solid tumors, regardless of tumor type.The CHMP’s recommendation will now be reviewed by the European Commission for marketing authorization in the European Union, and a final decision is expected in the second quarter of 2022.About Microsatellite Instability-High (MSI-H) and Deficient Mismatch Repair (dMMR)Microsatellite instability (MSI) and deficient mismatch repair (dMMR) are biomarkers that have been identified in many different types of cancer and that can be hereditary or random. MSI is a change that occurs in the DNA of certain cells, such as cancer cells, in which the number of repeated DNA bases in a microsatellite (which is a short, repeated sequence of DNA) is different from what it was when the microsatellite was inherited. dMMR describes cells that have mutations in certain genes involved in correcting mistakes made when DNA is copied into a cell when dividing. High levels of MSI (MSI-H) and dMMR can occur when a cell is unable to repair mistakes during that division process.About KEYTRUDA® (pembrolizumab) Injection, 100 mgKEYTRUDA is an anti-programmed death receptor-1 (PD-1) therapy that works by increasing the ability of the body’s immune system to help detect and fight tumor cells. KEYTRUDA is a humanized monoclonal antibody that blocks the interaction between PD-1 and its ligands, PD-L1 and PD-L2, thereby activating T lymphocytes which may affect both tumor cells and healthy cells.Merck has the industry’s largest immuno-oncology clinical research program. There are currently more than 1,700 trials studying KEYTRUDA across a wide variety of cancers and treatment settings. The KEYTRUDA clinical program seeks to understand the role of KEYTRUDA across cancers and the factors that may predict a patient's likelihood of benefitting from treatment with KEYTRUDA, including exploring several different biomarkers.https://www.keytruda.com/ Selected KEYTRUDA® (pembrolizumab) Indications in the U.S.MelanomaKEYTRUDA is indicated for the treatment of patients with unresectable or metastatic melanoma.KEYTRUDA is indicated for the adjuvant treatment of adult and pediatric (12 years and older) patients with stage IIB, IIC, or III melanoma following complete resection.Non-Small Cell Lung CancerKEYTRUDA, in combination with pemetrexed and platinum chemotherapy, is indicated for the first-line treatment of patients with metastatic nonsquamous non-small cell lung cancer (NSCLC), with no EGFR or ALK genomic tumor aberrations.KEYTRUDA, in combination with carboplatin and either paclitaxel or paclitaxel protein-bound, is indicated for the first-line treatment of patients with metastatic squamous NSCLC.KEYTRUDA, as a single agent, is indicated for the first-line treatment of patients with NSCLC expressing PD-L1 [tumor proportion score (TPS) ≥1%] as determined by an FDA-approved test, with no EGFR or ALK genomic tumor aberrations, and is:
- stage III where patients are not candidates for surgical resection or definitive chemoradiation, or
- metastatic.
KEYTRUDA, as a single agent, is indicated for the treatment of patients with metastatic NSCLC whose tumors express PD-L1 (TPS ≥1%) as determined by an FDA-approved test, with disease progression on or after platinum-containing chemotherapy. Patients with EGFR or ALK genomic tumor aberrations should have disease progression on FDA-approved therapy for these aberrations prior to receiving KEYTRUDA.Head and Neck Squamous Cell CancerKEYTRUDA, in combination with platinum and fluorouracil (FU), is indicated for the first-line treatment of patients with metastatic or with unresectable, recurrent head and neck squamous cell carcinoma (HNSCC).KEYTRUDA, as a single agent, is indicated for the first-line treatment of patients with metastatic or with unresectable, recurrent HNSCC whose tumors express PD-L1 [Combined Positive Score (CPS) ≥1] as determined by an FDA-approved test.KEYTRUDA, as a single agent, is indicated for the treatment of patients with recurrent or metastatic HNSCC with disease progression on or after platinum-containing chemotherapy.Classical Hodgkin LymphomaKEYTRUDA is indicated for the treatment of adult patients with relapsed or refractory classical Hodgkin lymphoma (cHL).KEYTRUDA is indicated for the treatment of pediatric patients with refractory cHL, or cHL that has relapsed after 2 or more lines of therapy.Primary Mediastinal Large B-Cell LymphomaKEYTRUDA is indicated for the treatment of adult and pediatric patients with refractory primary mediastinal large B-cell lymphoma (PMBCL), or who have relapsed after 2 or more prior lines of therapy.KEYTRUDA is not recommended for treatment of patients with PMBCL who require urgent cytoreductive therapy.Urothelial CarcinomaKEYTRUDA is indicated for the treatment of patients with locally advanced or metastatic urothelial carcinoma (mUC):
- who are not eligible for any platinum-containing chemotherapy, or
- who have disease progression during or following platinum-containing chemotherapy or within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy.
Non-muscle Invasive Bladder CancerKEYTRUDA is indicated for the treatment of patients with Bacillus Calmette-Guerin-unresponsive, high-risk, non-muscle invasive bladder cancer (NMIBC) with carcinoma in situ with or without papillary tumors who are ineligible for or have elected not to undergo cystectomy.Microsatellite Instability-High or Mismatch Repair Deficient CancerKEYTRUDA is indicated for the treatment of adult and pediatric patients with unresectable or metastatic microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) solid tumors that have progressed following prior treatment and who have no satisfactory alternative treatment options.This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials. The safety and effectiveness of KEYTRUDA in pediatric patients with MSI-H central nervous system cancers have not been established.Microsatellite Instability-High or Mismatch Repair Deficient Colorectal CancerKEYTRUDA is indicated for the treatment of patients with unresectable or metastatic MSI-H or dMMR colorectal cancer (CRC).Gastric CancerKEYTRUDA, in combination with trastuzumab, fluoropyrimidine- and platinum-containing chemotherapy, is indicated for the first-line treatment of patients with locally advanced unresectable or metastatic HER2-positive gastric or gastroesophageal junction (GEJ) adenocarcinoma.This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.Esophageal CancerKEYTRUDA is indicated for the treatment of patients with locally advanced or metastatic esophageal or gastroesophageal junction (GEJ) (tumors with epicenter 1 to 5 centimeters above the GEJ) carcinoma that is not amenable to surgical resection or definitive chemoradiation either:
- in combination with platinum- and fluoropyrimidine-based chemotherapy, or
- as a single agent after one or more prior lines of systemic therapy for patients with tumors of squamous cell histology that express PD-L1 (CPS ≥10) as determined by an FDA-approved test.
Cervical CancerKEYTRUDA, in combination with chemotherapy, with or without bevacizumab, is indicated for the treatment of patients with persistent, recurrent, or metastatic cervical cancer whose tumors express PD-L1 (CPS ≥1) as determined by an FDA-approved test.KEYTRUDA, as a single agent, is indicated for the treatment of patients with recurrent or metastatic cervical cancer with disease progression on or after chemotherapy whose tumors express PD-L1 (CPS ≥1) as determined by an FDA-approved test.Hepatocellular CarcinomaKEYTRUDA is indicated for the treatment of patients with hepatocellular carcinoma (HCC) who have been previously treated with sorafenib. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.Merkel Cell CarcinomaKEYTRUDA is indicated for the treatment of adult and pediatric patients with recurrent locally advanced or metastatic Merkel cell carcinoma (MCC). This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.Renal Cell CarcinomaKEYTRUDA, in combination with axitinib, is indicated for the first-line treatment of adult patients with advanced renal cell carcinoma (RCC).KEYTRUDA is indicated for the adjuvant treatment of patients with RCC at intermediate-high or high risk of recurrence following nephrectomy, or following nephrectomy and resection of metastatic lesions.Endometrial CarcinomaKEYTRUDA, as a single agent, is indicated for the treatment of patients with advanced endometrial carcinoma that is MSI-H or dMMR, as determined by an FDA-approved test, who have disease progression following prior systemic therapy in any setting and are not candidates for curative surgery or radiation.Tumor Mutational Burden-High CancerKEYTRUDA is indicated for the treatment of adult and pediatric patients with unresectable or metastatic tumor mutational burden-high (TMB-H) [≥10 mutations/megabase] solid tumors, as determined by an FDA-approved test, that have progressed following prior treatment and who have no satisfactory alternative treatment options. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials. The safety and effectiveness of KEYTRUDA in pediatric patients with TMB-H central nervous system cancers have not been established.Cutaneous Squamous Cell CarcinomaKEYTRUDA is indicated for the treatment of patients with recurrent or metastatic cutaneous squamous cell carcinoma (cSCC) or locally advanced cSCC that is not curable by surgery or radiation.Triple-Negative Breast CancerKEYTRUDA is indicated for the treatment of patients with high-risk early-stage triple-negative breast cancer (TNBC) in combination with chemotherapy as neoadjuvant treatment, and then continued as a single agent as adjuvant treatment after surgery.KEYTRUDA, in combination with chemotherapy, is indicated for the treatment of patients with locally recurrent unresectable or metastatic TNBC whose tumors express PD-L1 (CPS ≥10) as determined by an FDA-approved test. For more information about our oncology clinical trials, visit www.merck.com/clinicaltrials. For more information, visit www.merck.com and connect with us on Twitter, Facebook, Instagram, YouTube and LinkedIn. Please see Prescribing Information for KEYTRUDA (pembrolizumab) at http://www.merck.com/product/usa/pi_circulars/k/keytruda/keytruda_pi.pdf and Medication Guide for KEYTRUDA at http://www.merck.com/product/usa/pi_circulars/k/keytruda/keytruda_mg.pdf . Source: Merck & Co., Inc.
Merck's Keytruda gets EMA panel nod for expanded use in certain tumors in 5 cancers
Mar. 25, 2022 9:49 AM ET Merck & Co., Inc. (MRK) By: Ravikash, SA News Editor
- A committee of the European Medicines Agency (EMA) recommended the approval of expanded use of Merck's (NYSE:MRK) blockbuster drug Keytruda as a monotherapy for microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) tumors in five different types of cancers.
- https://seekingalpha.com/news/3817481-mercks-keytruda-gets-ema-panel-nod-for-expanded-use-in-certain-tumors-in-5-cancers
- https://seekingalpha.com/symbol/MRK
- https://www.keytruda.com/
- https://www.merck.com/
KEYTRUDA® (pembrolizumab)
CABOMETYX® (cabozantinib)
KEYTRUDA® (pembrolizumab)
Merck’s KEYTRUDA® (pembrolizumab) Significantly Improved Disease-Free Survival (DFS) Versus Placebo as Adjuvant Therapy in Patients With Stage IB-IIIA Non-Small Cell Lung Cancer (NSCLC) Regardless of PD-L1 Expression
March 17, 2022 2:15 pm ETFirst Phase 3 Study To Demonstrate Statistically Significant Improvement in DFS in the Adjuvant Setting for Patients With Stage IB-IIIA NSCLC Regardless of PD-L1 ExpressionKENILWORTH, N.J.--(BUSINESS WIRE)-- Merck (NYSE: MRK), known as MSD outside the United States and Canada, the European Organisation for Research and Treatment of Cancer (EORTC) and the European Thoracic Oncology Platform (ETOP) today announced results from the pivotal Phase 3 KEYNOTE-091 trial, also known as EORTC-1416-LCG/ETOP-8-15 – PEARLS. The study found that adjuvant treatment with KEYTRUDA significantly improved disease-free survival (DFS), one of the dual primary endpoints, reducing the risk of disease recurrence or death by 24% compared to placebo (hazard ratio [HR]=0.76 [95% CI, 0.63-0.91]; p=0.0014) in patients with stage IB (≥4 centimeters) to IIIA non-small cell lung cancer (NSCLC) following surgical resection regardless of PD-L1 expression. Median DFS was 53.6 months for KEYTRUDA versus 42.0 months for placebo, an improvement of nearly one year. These data are being presented today during a European Society for Medical Oncology (ESMO) Virtual Plenary and will be shared with regulatory authorities worldwide.“These are the first positive results for KEYTRUDA in the adjuvant setting for non-small cell lung cancer, and represent the sixth positive pivotal study evaluating a KEYTRUDA-based regimen in earlier stages of cancer,” said Dr. Roy Baynes, senior vice president and head of global clinical development, chief medical officer, Merck Research Laboratories. “KEYTRUDA has become foundational in the treatment of metastatic non-small cell lung cancer, and we are pleased to present these data showing the potential of KEYTRUDA to help more patients with lung cancer in earlier stages of disease. We thank the patients, their caregivers and investigators for participating in this study.”As previously announced, there was also an improvement in DFS for patients whose tumors express PD-L1 (tumor proportion score [TPS] ≥50%) treated with KEYTRUDA compared to placebo, the other dual primary endpoint; these results did not reach statistical significance per the pre-specified statistical plan (HR=0.82 [95% CI, 0.57-1.18]; p=0.14). Among these patients, median DFS was not reached in either arm. Additionally, a favorable trend in overall survival (OS), a key secondary endpoint, was observed for KEYTRUDA versus placebo regardless of PD-L1 expression (HR=0.87 [95% CI, 0.67-1.15]; p=0.17); these OS data are not mature and did not reach statistical significance at the time of this interim analysis. The trial will continue to evaluate DFS in patients whose tumors express high levels of PD-L1 (TPS ≥50%) and OS. The safety profile of KEYTRUDA in this study was consistent with that observed in previously reported studies.“Lung cancer is most treatable at earlier stages, and adding treatment after surgery may help reduce the risk of recurrence,” said Professor Mary O'Brien, consultant medical oncologist and head of the Lung Unit at The Royal Marsden NHS Foundation Trust and professor of practice (medical oncology) at Imperial College London, as well as co-principal investigator. “We are encouraged by these new Phase 3 data, as they represent the first time adjuvant immunotherapy has demonstrated a statistically significant and clinically meaningful improvement in disease-free survival for patients with stage IB-IIIA non-small cell lung cancer.”“While significant advancements have been made in the treatment of metastatic non-small cell lung cancer, there remains an unmet need for patients with earlier stages of this disease, as up to 43% of them will experience disease recurrence following surgery,” said Dr. Luis Paz-Ares, chair of the medical oncology department, Hospital Universitario Doce de Octubre, Madrid, Spain and co-principal investigator. “The positive disease-free survival data observed in this study with the use of KEYTRUDA in the adjuvant setting has the potential to have important implications for how we treat patients with stage IB-IIIA non-small cell lung cancer.”In addition to KEYNOTE-091, five other pivotal trials evaluating a KEYTRUDA-based regimen in patients with earlier stages of cancer met their primary endpoint(s). These trials included: KEYNOTE-716 in stage IIB and IIC melanoma; KEYNOTE-054 in stage III melanoma; KEYNOTE-564 in renal cell carcinoma; KEYNOTE-522 in triple-negative breast cancer; and KEYNOTE-057 in Bacillus Calmette-Guerin (BCG)-unresponsive, high-risk, non-muscle invasive bladder cancer.Merck has an extensive clinical development program in lung cancer and is advancing multiple registration-enabling studies, with research directed at earlier stages of disease and novel combinations. Key studies in earlier stages of NSCLC include KEYNOTE-091, KEYNOTE-671, KEYNOTE-867 and KEYLYNK-012.
Study Design and Additional Data From KEYNOTE-091KEYNOTE-091, also known as EORTC-1416-LCG/ETOP-8-15 – PEARLS, is a randomized, Phase 3 trial (ClinicalTrials.gov, NCT02504372) sponsored by Merck and conducted in collaboration with EORTC and ETOP evaluating KEYTRUDA compared to placebo for the adjuvant treatment of patients with stage IB (≥4 centimeters) to IIIA NSCLC following surgical resection (lobectomy or pneumonectomy) and with adjuvant chemotherapy when indicated. The dual primary endpoints are DFS in the overall population and in patients whose tumors express PD-L1 (TPS ≥50%). Disease-free survival is calculated as the time from randomization to the date of disease recurrence, occurrence of second primary lung cancer, occurrence of second malignancy, or death from any cause, whichever occurs first. The secondary endpoints include OS and lung cancer-specific survival (the time from randomization to date of death due to lung cancer specifically). The study randomized 1,177 patients (1:1) to receive either KEYTRUDA (200 mg intravenously [IV] every three weeks [Q3W] for one year or maximum 18 doses; n=590); or placebo (IV Q3W for one year or maximum 18 doses; n=587). The median number of doses was 17 for KEYTRUDA and 18 for placebo. As of data cut-off for this interim analysis (September 20, 2021), median time from randomization to data cut-off was 35.6 months (range, 16.5-68.0 months).Grade ≥3 adverse events occurred in 34.1% of patients receiving KEYTRUDA and 25.8% of patients receiving placebo. Adverse events resulting in discontinuation of any treatment occurred in 19.8% of patients receiving KEYTRUDA and 5.9% of patients receiving placebo; there were four treatment-related deaths in the KEYTRUDA arm and no treatment-related deaths in the placebo arm.
About KEYTRUDA® (pembrolizumab) Injection, 100 mgKEYTRUDA is an anti-programmed death receptor-1 (PD-1) therapy that works by increasing the ability of the body’s immune system to help detect and fight tumor cells. KEYTRUDA is a humanized monoclonal antibody that blocks the interaction between PD-1 and its ligands, PD-L1 and PD-L2, thereby activating T lymphocytes which may affect both tumor cells and healthy cells.Merck has the industry’s largest immuno-oncology clinical research program. There are currently more than 1,700 trials studying KEYTRUDA across a wide variety of cancers and treatment settings. The KEYTRUDA clinical program seeks to understand the role of KEYTRUDA across cancers and the factors that may predict a patient's likelihood of benefitting from treatment with KEYTRUDA, including exploring several different biomarkers.
Selected Indications for KEYTRUDA® (pembrolizumab) in the U.S.Non-Small Cell Lung CancerKEYTRUDA, in combination with pemetrexed and platinum chemotherapy, is indicated for the first-line treatment of patients with metastatic nonsquamous non-small cell lung cancer (NSCLC), with no EGFR or ALK genomic tumor aberrations.KEYTRUDA, in combination with carboplatin and either paclitaxel or paclitaxel protein-bound, is indicated for the first-line treatment of patients with metastatic squamous NSCLC.KEYTRUDA, as a single agent, is indicated for the first-line treatment of patients with NSCLC expressing PD-L1 [tumor proportion score (TPS) ≥1%] as determined by an FDA-approved test, with no EGFR or ALK genomic tumor aberrations, and is:
- stage III where patients are not candidates for surgical resection or definitive chemoradiation, or
- metastatic.
KEYTRUDA, as a single agent, is indicated for the treatment of patients with metastatic NSCLC whose tumors express PD-L1 (TPS ≥1%) as determined by an FDA-approved test, with disease progression on or after platinum-containing chemotherapy. Patients with EGFR or ALK genomic tumor aberrations should have disease progression on FDA-approved therapy for these aberrations prior to receiving KEYTRUDA.See additional selected indications for KEYTRUDA in the U.S. after the Selected Important Safety Information
Additional Indications for KEYTRUDA in the U.S.
MelanomaKEYTRUDA is indicated for the treatment of patients with unresectable or metastatic melanoma.KEYTRUDA is indicated for the adjuvant treatment of adult and pediatric (12 years and older) patients with stage IIB, IIC, or III melanoma following complete resection.Head and Neck Squamous Cell CancerKEYTRUDA, in combination with platinum and fluorouracil (FU), is indicated for the first-line treatment of patients with metastatic or with unresectable, recurrent head and neck squamous cell carcinoma (HNSCC).KEYTRUDA, as a single agent, is indicated for the first-line treatment of patients with metastatic or with unresectable, recurrent HNSCC whose tumors express PD-L1 [combined positive score (CPS) ≥1] as determined by an FDA-approved test.KEYTRUDA, as a single agent, is indicated for the treatment of patients with recurrent or metastatic HNSCC with disease progression on or after platinum-containing chemotherapy.Classical Hodgkin LymphomaKEYTRUDA is indicated for the treatment of adult patients with relapsed or refractory classical Hodgkin lymphoma (cHL).KEYTRUDA is indicated for the treatment of pediatric patients with refractory cHL, or cHL that has relapsed after 2 or more lines of therapy.Primary Mediastinal Large B-Cell LymphomaKEYTRUDA is indicated for the treatment of adult and pediatric patients with refractory primary mediastinal large B-cell lymphoma (PMBCL), or who have relapsed after 2 or more prior lines of therapy.KEYTRUDA is not recommended for treatment of patients with PMBCL who require urgent cytoreductive therapy.Urothelial CarcinomaKEYTRUDA is indicated for the treatment of patients with locally advanced or metastatic urothelial carcinoma (mUC):
- who are not eligible for any platinum-containing chemotherapy, or
- who have disease progression during or following platinum-containing chemotherapy or within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy.
Non-muscle Invasive Bladder CancerKEYTRUDA is indicated for the treatment of patients with Bacillus Calmette-Guerin (BCG)-unresponsive, high-risk, non-muscle invasive bladder cancer (NMIBC) with carcinoma in situ with or without papillary tumors who are ineligible for or have elected not to undergo cystectomy.Microsatellite Instability-High or Mismatch Repair Deficient CancerKEYTRUDA is indicated for the treatment of adult and pediatric patients with unresectable or metastatic microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) solid tumors that have progressed following prior treatment and who have no satisfactory alternative treatment options.This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials. The safety and effectiveness of KEYTRUDA in pediatric patients with MSI-H central nervous system cancers have not been established.Microsatellite Instability-High or Mismatch Repair Deficient Colorectal CancerKEYTRUDA is indicated for the treatment of patients with unresectable or metastatic MSI-H or dMMR colorectal cancer (CRC).Gastric CancerKEYTRUDA, in combination with trastuzumab, fluoropyrimidine- and platinum-containing chemotherapy, is indicated for the first-line treatment of patients with locally advanced unresectable or metastatic HER2-positive gastric or gastroesophageal junction (GEJ) adenocarcinoma.This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.Esophageal CancerKEYTRUDA is indicated for the treatment of patients with locally advanced or metastatic esophageal or gastroesophageal (GEJ) (tumors with epicenter 1 to 5 centimeters above the GEJ) carcinoma that is not amenable to surgical resection or definitive chemoradiation either:
- in combination with platinum- and fluoropyrimidine-based chemotherapy, or
- as a single agent after one or more prior lines of systemic therapy for patients with tumors of squamous cell histology that express PD-L1 (CPS ≥10) as determined by an FDA-approved test.
Cervical CancerKEYTRUDA, in combination with chemotherapy, with or without bevacizumab, is indicated for the treatment of patients with persistent, recurrent, or metastatic cervical cancer whose tumors express PD-L1 (CPS ≥1) as determined by an FDA-approved test.KEYTRUDA, as a single agent, is indicated for the treatment of patients with recurrent or metastatic cervical cancer with disease progression on or after chemotherapy whose tumors express PD-L1 (CPS ≥1) as determined by an FDA-approved test.Hepatocellular CarcinomaKEYTRUDA is indicated for the treatment of patients with hepatocellular carcinoma (HCC) who have been previously treated with sorafenib. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.Merkel Cell CarcinomaKEYTRUDA is indicated for the treatment of adult and pediatric patients with recurrent locally advanced or metastatic Merkel cell carcinoma (MCC). This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.Renal Cell CarcinomaKEYTRUDA, in combination with axitinib, is indicated for the first-line treatment of adult patients with advanced renal cell carcinoma (RCC).KEYTRUDA is indicated for the adjuvant treatment of patients with RCC at intermediate-high or high risk of recurrence following nephrectomy, or following nephrectomy and resection of metastatic lesions.Tumor Mutational Burden-High CancerKEYTRUDA is indicated for the treatment of adult and pediatric patients with unresectable or metastatic tumor mutational burden-high (TMB-H) [≥10 mutations/megabase] solid tumors, as determined by an FDA-approved test, that have progressed following prior treatment and who have no satisfactory alternative treatment options. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials. The safety and effectiveness of KEYTRUDA in pediatric patients with TMB-H central nervous system cancers have not been established.Cutaneous Squamous Cell CarcinomaKEYTRUDA is indicated for the treatment of patients with recurrent or metastatic cutaneous squamous cell carcinoma (cSCC) or locally advanced cSCC that is not curable by surgery or radiation.Triple-Negative Breast CancerKEYTRUDA is indicated for the treatment of patients with high-risk early-stage triple-negative breast cancer (TNBC) in combination with chemotherapy as neoadjuvant treatment, and then continued as a single agent as adjuvant treatment after surgery.KEYTRUDA, in combination with chemotherapy, is indicated for the treatment of patients with locally recurrent unresectable or metastatic TNBC whose tumors express PD-L1 (CPS ≥10) as determined by an FDA-approved test.
For more information, visit www.merck.com and connect with us on Twitter, Facebook, Instagram, YouTube and LinkedIn
Please see Prescribing Information for KEYTRUDA (pembrolizumab) at http://www.merck.com/product/usa/pi_circulars/k/keytruda/keytruda_pi.pdf and Medication Guide for KEYTRUDA at http://www.merck.com/product/usa/pi_circulars/k/keytruda/keytruda_mg.pdf . Source: Merck & Co., Inc.
Merck Keytruda's add on use in early- stage lung cancer cuts death risk by 24% in study
Mar. 18, 2022 4:55 AM ET
By: Ravikash, SA News Editor Merck (NYSE:MRK) said a phase 3 trial showed that postsurgical use of Keytruda significantly improved disease-free survival (DFS), reducing the risk of disease recurrence or death by 24% compared to placebo in patients with stage IB-IIIA non-small cell lung cancer (NSCLC) regardless of PD-L1 expression.https://seekingalpha.com/news/3814881-mercks-keytruda-add-on-use-in-early-stage-lung-cancer-cuts-death-risk-by-24-in-studyhttps://seekingalpha.com/symbol/MRKhttps://www.keytruda.com/
Lynparza (olaparib)
Trodelvy® (sacituzumab govitecan-hziy)
KEYTRUDA® (pembrolizumab)
Lynparza approved in the US as adjuvant treatment for patients with germline BRCA-mutated HER2-negative high-risk early breast cancer
PUBLISHED11 March 2022
11 March 2022 21:00 GMT
First and only approved medicine targeting BRCA mutations in early breast cancer
New data show Lynparza demonstrated overall survival benefit in early breast cancer
AstraZeneca and MSD’s Lynparza (olaparib) has been approved in the US for the adjuvant treatment of patients with germline BRCA-mutated (gBRCAm) HER2-negative high-risk early breast cancer who have already been treated with chemotherapy either before or after surgery.The approval by the US Food and Drug Administration (FDA) was based on results from the OlympiA Phase III trial presented during the 2021 American Society of Clinical Oncology Annual Meeting and published in The New England Journal of Medicine.1In the trial, Lynparza demonstrated a statistically significant and clinically meaningful improvement in invasive disease-free survival (iDFS), reducing the risk of invasive breast cancer recurrences, second cancers or death, by 42% versus placebo (based on a hazard ratio [HR] of 0.58; 95% confidence interval [CI] 0.46-0.74; p<0.0001).New updated results from the OlympiA trial also showed Lynparza demonstrated a statistically significant and clinically meaningful improvement in the key secondary endpoint of overall survival (OS), reducing the risk of death by 32% versus placebo (based on a HR of 0.68; 95% CI 0.50-0.91; p=0.0091). The safety and tolerability profile of Lynparza in this trial was in line with that observed in prior clinical trials. The OS data will be presented at an upcoming European Society for Medical Oncology virtual plenary on 16 March 2022.Breast cancer is the most diagnosed cancer worldwide with an estimated 2.3 million patients diagnosed in 2020.2 Almost 91% of all breast cancer patients in the US are diagnosed at an early stage of disease and BRCA mutations are found in approximately 5-10% of patients.3,4Professor Andrew Tutt, Global Chair of the OlympiA Phase III trial and Professor of Oncology at The Institute of Cancer Research, London and King’s College London, said: “Today’s approval of olaparib is great news for patients with a specific inherited form of breast cancer. Most breast cancers are identified in the early stages and many patients will do very well, but for those with higher risk disease at diagnosis, the risk of cancer returning can be unacceptably high and new treatment options are needed. OlympiA has shown that identifying a BRCA1/2 mutation in women with high risk disease opens the additional option of eligibility for olaparib treatment, which reduces the risk of recurrence and improves survival for these breast cancer patients.”Dave Fredrickson, Executive Vice President, Oncology Business Unit, AstraZeneca, said: “This important approval gives early-stage breast cancer patients in the US with a germline BRCA mutation a new targeted therapy option in the adjuvant setting starting today. Lynparza reduces the risk of disease recurrence in these high-risk patients and now new data confirm it also significantly extends patients’ lives versus placebo. These data underline the importance of germline BRCA testing as soon as possible after diagnosis to identify patients that may be eligible for Lynparza.”Roy Baynes, Senior Vice President and Head of Global Clinical Development, Chief Medical Officer, MSD Research Laboratories, said: “For patients with germline BRCA-mutated, HER2-negative high-risk early breast cancer, who often present with more aggressive disease, today’s approval is an important step forward. Compared to placebo, Lynparza as adjuvant treatment offers these patients the potential to live longer without their cancer recurring. We thank the patients, caregivers and healthcare providers for their participation in the OlympiA trial.”Lynparza is now indicated for the adjuvant treatment of adult patients with deleterious or suspected deleterious gBRCAm HER2-negative high-risk early breast cancer who have been treated with neoadjuvant or adjuvant chemotherapy. Patients are to be selected for treatment based on an FDA-approved companion diagnostic test for Lynparza.Lynparza is approved in the US, EU, Japan and several other countries for the treatment of patients with gBRCAm, HER2-negative, metastatic breast cancer previously treated with chemotherapy based on results from the OlympiAD Phase III trial. In the EU, this indication also includes patients with locally advanced breast cancer.
Lynparza
Lynparza (olaparib) is a first-in-class PARP inhibitor and the first targeted treatment to block DNA damage response (DDR) in cells/tumours harbouring a deficiency in homologous recombination repair (HRR), such as those with mutations in BRCA1 and/or BRCA2, or those where deficiency is induced by other agents (such as new hormonal agents – NHAs).Inhibition of PARP proteins with Lynparza leads to the trapping of PARP bound to DNA single-strand breaks, stalling of replication forks, their collapse and the generation of DNA double-strand breaks and cancer cell death.Lynparza is currently approved in a number of countries across PARP-dependent tumour types with defects and dependencies in the DDR pathway including maintenance treatment of platinum-sensitive relapsed ovarian cancer and as both monotherapy and in combination with bevacizumab for the 1st-line maintenance treatment of BRCA-mutated (BRCAm) and homologous recombination repair deficient (HRD)-positive advanced ovarian cancer, respectively; for germline BRCAm, HER2-negative metastatic breast cancer (in the EU this includes locally advanced breast cancer); for germline BRCAm metastatic pancreatic cancer; and HRR gene-mutated metastatic castration-resistant prostate cancer (BRCAm only in the EU and Japan).Lynparza, which is being jointly developed and commercialised by AstraZeneca and MSD, is the foundation of AstraZeneca's industry-leading portfolio of potential new medicines targeting DDR mechanisms in cancer cells.https://www.lynparza.com/
The AstraZeneca and MSD strategic oncology collaboration
In July 2017, AstraZeneca and Merck & Co., Inc., Kenilworth, NJ, US, known as MSD outside the US and Canada, announced a global strategic oncology collaboration to co-develop and co-commercialise Lynparza, the world’s first PARP inhibitor, and Koselugo (selumetinib), a mitogen-activated protein kinase (MEK) inhibitor, for multiple cancer types.Working together, the companies will develop Lynparza and Koselugo in combination with other potential new medicines and as monotherapies. The companies will develop Lynparza and Koselugo in combination with their respective PD-L1 and PD-1 medicines independently.
Please visit astrazeneca.com and follow the Company on Twitter @AstraZeneca.
AstraZeneca and Merck's Lynparza gets FDA nod for early breast cancer
Mar. 11, 2022 6:42 PM ET
By: Jonathan Block, SA News Editor
- The U.S. FDA has granted an additional indication for AstraZeneca (NASDAQ:AZN) and Merck's (NYSE:MRK) Lynparza (olaparib) as an adjuvant treatment for a type of early-stage breast cancer.
- https://seekingalpha.com/news/3812883-astrazeneca-and-merck-lynparza-gets-fda-nod-for-early-breast-cancer
- https://seekingalpha.com/symbol/AZN
- https://seekingalpha.com/symbol/MRK
- https://www.lynparza.com/
Jardiance® (empagliflozin)
Trodelvy® (sacituzumab govitecan-hziy)
Trodelvy® (sacituzumab govitecan-hziy)
Jardiance® (empagliflozin) becomes the first and only approved treatment in Europe for adults with symptomatic chronic heart failure regardless of ejection fraction
Ingelheim, Monday, 03/07/2022 - 08:00
- The breakthrough approval expands the existing indication of Jardiance® to include adults with heart failure with preserved ejection fraction (HFpEF), an underserved patient population that previously had no approved therapies in Europe
- European marketing authorization follows the U.S. Food and Drug Administration (FDA)’s approval received on 24 February 2022
Ingelheim, Germany, 07 March 2022 – The European Commission (EC) has granted marketing authorization for Jardiance® (empagliflozin) as a treatment for adults with symptomatic chronic heart failure, Boehringer Ingelheim and Eli Lilly and Company have announced.1 The landmark approval makes Jardiance® the first and only approved treatment for all adults with symptomatic chronic heart failure, which includes patients across the full spectrum of LVEF, including both heart failure with reduced and preserved ejection fraction (HFrEF and HFpEF). About the EMPEROR heart failure clinical trials7,8The EMPEROR (EMPagliflozin outcomE tRial in patients with chrOnic heaRt failure) chronic heart failure trials were two Phase III, randomized, double-blind trials that investigated once-daily empagliflozin compared to placebo in adults with chronic HFrEF or HFpEF, with or without diabetes:
- EMPEROR-Reduced [NCT03057977] investigated the safety and efficacy of empagliflozin in patients with chronic HFrEF. o Primary endpoint: time to first event of adjudicated cardiovascular death or adjudicated hospitalization for heart failure o Number of patients: 3,730 o Completion: 2020
- EMPEROR-Preserved [NCT03057951] investigated the safety and efficacy of empagliflozin in patients with chronic HFpEF. o Primary endpoint: time to first event of adjudicated cardiovascular death or adjudicated hospitalization for heart failure o Number of patients: 5,988 o Completion: 2021
About the EMPOWER programThe Alliance has developed the EMPOWER program to explore the impact of empagliflozin on major clinical cardiovascular and renal outcomes in a spectrum of cardio-renal-metabolic conditions. Cardio-renal-metabolic conditions are the leading cause of mortality worldwide and account for up to 20 million deaths annually.9 Through the EMPOWER program, Boehringer Ingelheim and Lilly are working to advance knowledge of these interconnected systems and create care which offers integrated, multi-organ benefits. Comprised of nine clinical trials and two real-world evidence studies, EMPOWER reinforces the long-term commitment of the Alliance to improve outcomes for people living with cardio-renal-metabolic conditions. With more than 400,000 adults enrolled worldwide in studies, it is one of the broadest and most comprehensive clinical programs for an SGLT2 inhibitor to date.
About empagliflozinEmpagliflozin (marketed as Jardiance®) is an oral, once-daily, highly selective sodium-glucose cotransporter 2 (SGLT2) inhibitor and the first type 2 diabetes medicine to include cardiovascular death risk reduction data in its label in several countries.18,19https://www.jardiance.com/
Boehringer Ingelheim and Eli Lilly and Company
In January 2011, Boehringer Ingelheim and Eli Lilly and Company announced an Alliance that centers on compounds representing several of the largest diabetes treatment classes. Depending on geographies, the companies either co-promote or separately promote the respective molecules each contributing to the Alliance. The Alliance leverages the strengths of two of the world’s leading pharmaceutical companies to focus on patient needs. By joining forces, the companies demonstrate their commitment, not only to the care of people with diabetes, but also to investigating the potential to address areas of unmet medical need. Clinical trials have been initiated to evaluate the impact of empagliflozin on people living with heart failure or chronic kidney disease.
About Boehringer Ingelheim
Boehringer Ingelheim is working on breakthrough therapies that improve the lives of humans and animals. As a leading research-driven biopharmaceutical company, the company creates value through innovation in areas of high unmet medical need. Founded in 1885 and family-owned ever since, Boehringer Ingelheim takes a long-term perspective. Around 52,000 employees serve more than 130 markets in the three business areas, Human Pharma, Animal Health, and Biopharmaceutical Contract Manufacturing. Learn more at www.boehringer-ingelheim.com.
About Eli Lilly and Company
Lilly is a global health care leader that unites caring with discovery to create medicines that make life better for people around the world. We were founded more than a century ago by a man committed to creating high-quality medicines that meet real needs, and today we remain true to that mission in all our work. Across the globe, Lilly employees work to discover and bring life-changing medicines to those who need them, improve the understanding and management of disease, and give back to communities through philanthropy and volunteerism. To learn more about Lilly, please visit us at lilly.com and lilly.com/newsroom.
Lilly, Boehringer Ingelheim's Jardiance gets EU approval for expanded use in heart failure
Mar. 08, 2022 5:42 AM ET
By: Ravikash, SA News Editor
- The European Commission (EC) approved the expanded use of Eli Lilly (NYSE:LLY) and Boehringer Ingelheim's Jardiance (empagliflozin) to treat adults with symptomatic chronic heart failure.
- https://seekingalpha.com/news/3810496-lilly-boehringer-ingelheims-jardiance-gets-eu-approval-for-expanded-use-in-heart-failure
- https://seekingalpha.com/symbol/LLY
- https://www.jardiance.com/
- https://www.lilly.com/
Trodelvy® (sacituzumab govitecan-hziy)
Trodelvy® (sacituzumab govitecan-hziy)
Trodelvy® (sacituzumab govitecan-hziy)
March 07, 2022
Phase 3 TROPiCS-02 Study Met the Primary Endpoint of Progression-Free Survival in Late-Line HR+/HER2- Metastatic Breast Cancer
– Study Will Continue to Follow Patients for Overall Survival, a Key Secondary Endpoint –FOSTER CITY, Calif.--(BUSINESS WIRE)-- Gilead Sciences, Inc. (Nasdaq: GILD) today announced results from the Phase 3 TROPiCS-02 study evaluating Trodelvy® (sacituzumab govitecan-hziy) in patients with HR+/HER2- metastatic breast cancer who received prior endocrine therapy, CDK4/6 inhibitors and two to four lines of chemotherapy. The study met its primary endpoint with a statistically significant improvement in progression-free survival (PFS) versus physician’s choice of chemotherapy. The trial targeted a 30% reduction in the risk of disease progression or death. The primary endpoint results were consistent with those observed in the Phase 1/2 IMMU-132-01 study in a subset of HR+/HER2- metastatic breast cancer patients.1 The first interim analysis of the key secondary endpoint of overall survival in the TROPiCS-02 study demonstrated a trend in improvement for overall survival. Patients will be followed for a subsequent overall survival analysis. The safety profile for Trodelvy was consistent with prior studies, and no new safety concerns emerged in this patient population.“Trodelvy demonstrated consistent activity in this difficult-to-treat patient population,” said Merdad Parsey, MD, PhD, Chief Medical Officer, Gilead Sciences. “We are evaluating the data and will explore potential pathways with regulatory authorities to bring Trodelvy to this group of patients. As we work to expand the patient benefit of Trodelvy beyond its current indications for second-line metastatic triple-negative breast cancer and accelerated approval in second-line metastatic bladder cancer, we are pursuing studies across multiple tumor types and earlier lines of therapy.”“HR+/HER2- breast cancer accounts for approximately 70% of all breast cancer cases. Patients with advanced breast cancer may eventually develop endocrine resistance, then resistance to a limited set of sequential chemotherapy options,” said Hope Rugo, MD, Professor of Medicine and Director, Breast Oncology and Clinical Trials Education at the University of California San Francisco Comprehensive Cancer Center. “These data show the potential for Trodelvy to address an important unmet need for patients with HR+/HER2- metastatic breast cancer who have been heavily pretreated.”Detailed results from TROPiCS-02 will be presented at an upcoming medical conference.Gilead has filed a current report on Form 8-K that includes this press release and some FAQs related to the information in this release. The information in this press release should be read in conjunction with the FAQs.Trodelvy has not been approved by any regulatory agency for the treatment of HR+/HER2- metastatic breast cancer. Its safety and efficacy have not been established for this indication. Trodelvy has a Boxed Warning for severe or life-threatening neutropenia and severe diarrhea; please see below for additional Important Safety Information.
About the TROPiCS-02 Study
The TROPiCS-02 study is a global, multicenter, open-label, Phase 3 study, randomized 1:1 to evaluate Trodelvy versus physician’s choice of chemotherapy (eribulin, capecitabine, gemcitabine, or vinorelbine) in 543 patients with HR+/HER2- metastatic breast cancer who were previously treated with endocrine therapy, CDK4/6 inhibitors and two to four lines of chemotherapy. The primary endpoint is progression-free survival per Response Evaluation Criteria in Solid Tumors (RECIST 1.1) as assessed by blinded independent central review for participants treated with Trodelvy compared to those treated with chemotherapy. The trial targets a 30% reduction in the risk of disease progression or death and is powered to detect a statistically significant difference of at least 0.9 months in median PFS. Secondary endpoints include overall survival, duration of response, clinical benefit rate and overall response rate as well as assessment of safety and tolerability and quality of life measures. More information about TROPiCS-02 is available at https://clinicaltrials.gov/ct2/show/NCT03901339.
About Trodelvy
Trodelvy® (sacituzumab govitecan-hziy) is a first-in-class Trop-2 directed antibody-drug conjugate. Trop-2 is a cell surface antigen highly expressed in multiple tumor types, including in more than 90% of breast and bladder cancers. Trodelvy is intentionally designed with a proprietary hydrolyzable linker attached to SN-38, a topoisomerase I inhibitor payload. This unique combination delivers potent activity to both Trop-2 expressing cells and the microenvironment.Trodelvy is approved in more than 35 countries, with multiple additional regulatory reviews underway worldwide, for the treatment of adult patients with unresectable locally advanced or metastatic triple-negative breast cancer (TNBC) who have received two or more prior systemic therapies, at least one of them for metastatic disease. Trodelvy is also approved in the U.S. under the accelerated approval pathway for the treatment of adult patients with locally advanced or metastatic urothelial cancer (UC) who have previously received a platinum-containing chemotherapy and either programmed death receptor-1 (PD-1) or programmed death-ligand 1 (PD-L1) inhibitor.Trodelvy is also being developed for potential investigational use in other TNBC and metastatic UC populations, as well as a range of tumor types where Trop-2 is highly expressed, including hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) metastatic breast cancer, metastatic non-small cell lung cancer (NSCLC), metastatic small cell lung cancer (SCLC), head and neck cancer, and endometrial cancer.
U.S. Indication for Trodelvy
In the United States, Trodelvy is indicated for the treatment of:
- Adult patients with unresectable locally advanced or metastatic TNBC who have received two or more prior systemic therapies, at least one of them for metastatic disease.
- Adult patients with locally advanced or metastatic UC who have previously received a platinum-containing chemotherapy and either programmed death receptor-1 (PD-1) or programmed death-ligand 1 (PD-L1) inhibitor. This indication is approved under accelerated approval based on tumor response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.
Please see full Prescribing Information, including BOXED WARNING. U.S. Prescribing Information for Trodelvy including BOXED WARNING, is available at www.gilead.com.Trodelvy, Gilead and the Gilead logo are trademarks of Gilead Sciences, Inc., or its related companies.For more information about Gilead, please visit the company’s website at www.gilead.com, follow Gilead on Twitter
View source version on businesswire.com: https://www.businesswire.com/news/home/20220306005060/en/ Source: Gilead Sciences, Inc.
Gilead's Trodelvy meets primary endpoint in HR+/HER2- metastatic breast cancer trial
Mar. 07, 2022 9:01 AM ET
By: Jonathan Block, SA News Editor4 Comments
- Gilead Sciences' (NASDAQ:GILD) Trodelvy (sacituzumab) met its primary endpoint in a late-stage trial in patients with HR+/HER2- metastatic breast cancer.
- https://seekingalpha.com/news/3810179-gilead-trodelvy-meets-primary-endpoint-in-hr-her2-metastatic-breast-cancer-trial
- https://seekingalpha.com/symbol/GILD
- https://www.trodelvy.com/
KEYTRUDA® (pembrolizumab)
Opdivo® (nivolumab) with Chemotherapy
Opdivo® (nivolumab) with Chemotherapy
Merck’s KEYTRUDA® (pembrolizumab) Demonstrated Significant Improvement in Distant Metastasis-Free Survival (DMFS) Compared to Placebo as Adjuvant Therapy for Patients With Resected Stage IIB and IIC Melanoma in Phase 3 KEYNOTE-716 Trial
March 7, 2022 6:45 am ET
New Results Build on Previously Reported Significant Recurrence-Free Survival (RFS) Benefit Seen in These PatientsKENILWORTH, N.J.--(BUSINESS WIRE)-- Merck (NYSE: MRK), known as MSD outside the United States and Canada, today announced that the Phase 3 KEYNOTE-716 trial investigating KEYTRUDA, Merck’s anti-PD-1 therapy, as adjuvant treatment for patients with resected stage IIB and IIC melanoma met its key secondary endpoint of distant metastasis-free survival (DMFS) at a pre-specified interim analysis. In the trial, adjuvant treatment with KEYTRUDA demonstrated a statistically significant improvement in the endpoint of DMFS compared to placebo in these patients. No new safety signals were observed.At this interim analysis, treatment with KEYTRUDA also continued to show an improvement in recurrence-free survival (RFS) compared to placebo. As previously reported, KEYNOTE-716 met the primary endpoint of RFS at the first interim analysis (HR=0.65 [95% CI, 0.46-0.92]; p=0.00658), which supported U.S. Food and Drug Administration approval for this indication in December 2021. Full results from this analysis of KEYNOTE-716 will be presented at an upcoming medical meeting.“Patients with melanoma that has spread to distant sites have a significantly worse prognosis and the goal of adjuvant therapy is to delay disease recurrence, especially distant metastases,” said Dr. Scot Ebbinghaus, vice president, clinical research, Merck Research Laboratories. “In KEYNOTE-716, adjuvant treatment with KEYTRUDA first showed a significant improvement in recurrence-free survival and has now demonstrated a significant improvement in the time until the first diagnosis of a distant metastasis compared to placebo. The distant metastasis-free survival data from KEYNOTE-716 reinforce the evidence for KEYTRUDA as adjuvant therapy in stage IIB and IIC melanoma.”To date, KEYTRUDA has shown significant improvements in RFS and DMFS compared to placebo across resected stage IIB and stage IIC (KEYNOTE-716) and stage III melanoma (EORTC1325/KEYNOTE-054: RFS HR=0.57 [95% CI, 0.46, 0.70] p<0.001; DMFS HR=0.60 [95% CI, 0.49-0.73]; p<0.001).In the U.S., KEYTRUDA is approved for the adjuvant treatment of adult and pediatric (12 years and older) patients with stage IIB, IIC or III melanoma following complete resection. Additional global regulatory submissions based on KEYNOTE-716 are ongoing.
About KEYNOTE-716
KEYNOTE-716 (ClinicalTrials.gov, NCT03553836) is a multicenter, randomized, double-blind, placebo-controlled Phase 3 trial that enrolled 976 patients (12 years and older) with resected stage IIB or IIC melanoma. The primary endpoint of the trial is RFS, and secondary endpoints include DMFS and overall survival (OS). Following complete surgical resection, patients were randomized to KEYTRUDA 200 mg or the pediatric (≥12 years old) dose of KEYTRUDA 2 mg/kg intravenously (up to a maximum of 200 mg) every three weeks or placebo for up to one year until disease recurrence or unacceptable toxicity.
About EORTC1325/KEYNOTE-054
EORTC1325/KEYNOTE-054 (ClinicalTrials.gov, NCT02362594) is a multicenter, randomized, double-blind, placebo-controlled Phase 3 trial sponsored by Merck and conducted in collaboration with the European Organisation for Research and Treatment of Cancer that enrolled 1,019 patients with completely resected stage IIIA (>1 mm lymph node metastasis), IIIB, or IIIC melanoma who were randomized 1:1 to receive KEYTRUDA 200 mg every three weeks or placebo for up to one year or until disease recurrence or unacceptable toxicity. The co-primary endpoints are RFS for all patients and RFS in patients whose tumors expressed PD-L1. Secondary endpoints include DMFS and OS in all patients and in patients whose tumors expressed PD-L1.
About KEYTRUDA® (pembrolizumab) Injection, 100 mg
KEYTRUDA is an anti-programmed death receptor-1 (PD-1) therapy that works by increasing the ability of the body’s immune system to help detect and fight tumor cells. KEYTRUDA is a humanized monoclonal antibody that blocks the interaction between PD-1 and its ligands, PD-L1 and PD-L2, thereby activating T lymphocytes which may affect both tumor cells and healthy cells.Merck has the industry’s largest immuno-oncology clinical research program. There are currently more than 1,700 trials studying KEYTRUDA across a wide variety of cancers and treatment settings. The KEYTRUDA clinical program seeks to understand the role of KEYTRUDA across cancers and the factors that may predict a patient's likelihood of benefitting from treatment with KEYTRUDA, including exploring several different biomarkers.
Selected KEYTRUDA® (pembrolizumab) Indications in the U.S.
MelanomaKEYTRUDA is indicated for the treatment of patients with unresectable or metastatic melanoma.KEYTRUDA is indicated for the adjuvant treatment of adult and pediatric (12 years and older) patients with stage IIB, IIC, or III melanoma following complete resection.See additional selected KEYTRUDA indications in the U.S. after the Selected Important Safety Information
Additional Selected KEYTRUDAIndications in the U.S.
Non-Small Cell Lung CancerKEYTRUDA, in combination with pemetrexed and platinum chemotherapy, is indicated for the first-line treatment of patients with metastatic nonsquamous non-small cell lung cancer (NSCLC), with no EGFR or ALK genomic tumor aberrations.KEYTRUDA, in combination with carboplatin and either paclitaxel or paclitaxel protein-bound, is indicated for the first-line treatment of patients with metastatic squamous NSCLC.KEYTRUDA, as a single agent, is indicated for the first-line treatment of patients with NSCLC expressing PD-L1 [tumor proportion score (TPS) ≥1%] as determined by an FDA-approved test, with no EGFR or ALK genomic tumor aberrations, and is:
- stage III where patients are not candidates for surgical resection or definitive chemoradiation, or
- metastatic.
KEYTRUDA, as a single agent, is indicated for the treatment of patients with metastatic NSCLC whose tumors express PD-L1 (TPS ≥1%) as determined by an FDA-approved test, with disease progression on or after platinum-containing chemotherapy. Patients with EGFR or ALK genomic tumor aberrations should have disease progression on FDA-approved therapy for these aberrations prior to receiving KEYTRUDA.Head and Neck Squamous Cell CancerKEYTRUDA, in combination with platinum and fluorouracil (FU), is indicated for the first-line treatment of patients with metastatic or with unresectable, recurrent head and neck squamous cell carcinoma (HNSCC).KEYTRUDA, as a single agent, is indicated for the first-line treatment of patients with metastatic or with unresectable, recurrent HNSCC whose tumors express PD-L1 [combined positive score (CPS) ≥1] as determined by an FDA-approved test.KEYTRUDA, as a single agent, is indicated for the treatment of patients with recurrent or metastatic HNSCC with disease progression on or after platinum-containing chemotherapy.Classical Hodgkin LymphomaKEYTRUDA is indicated for the treatment of adult patients with relapsed or refractory classical Hodgkin lymphoma (cHL).KEYTRUDA is indicated for the treatment of pediatric patients with refractory cHL, or cHL that has relapsed after 2 or more lines of therapy.Primary Mediastinal Large B-Cell LymphomaKEYTRUDA is indicated for the treatment of adult and pediatric patients with refractory primary mediastinal large B-cell lymphoma (PMBCL), or who have relapsed after 2 or more prior lines of therapy.KEYTRUDA is not recommended for treatment of patients with PMBCL who require urgent cytoreductive therapy.Urothelial CarcinomaKEYTRUDA is indicated for the treatment of patients with locally advanced or metastatic urothelial carcinoma (mUC):
- who are not eligible for any platinum-containing chemotherapy, or
- who have disease progression during or following platinum-containing chemotherapy or within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy.
Non-muscle Invasive Bladder CancerKEYTRUDA is indicated for the treatment of patients with Bacillus Calmette-Guerin (BCG)-unresponsive, high-risk, non-muscle invasive bladder cancer (NMIBC) with carcinoma in situ with or without papillary tumors who are ineligible for or have elected not to undergo cystectomy.Microsatellite Instability-High or Mismatch Repair Deficient CancerKEYTRUDA is indicated for the treatment of adult and pediatric patients with unresectable or metastatic microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) solid tumors that have progressed following prior treatment and who have no satisfactory alternative treatment options.This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials. The safety and effectiveness of KEYTRUDA in pediatric patients with MSI-H central nervous system cancers have not been established.Microsatellite Instability-High or Mismatch Repair Deficient Colorectal CancerKEYTRUDA is indicated for the treatment of patients with unresectable or metastatic MSI-H or dMMR colorectal cancer (CRC).Gastric CancerKEYTRUDA, in combination with trastuzumab, fluoropyrimidine- and platinum-containing chemotherapy, is indicated for the first-line treatment of patients with locally advanced unresectable or metastatic HER2-positive gastric or gastroesophageal junction (GEJ) adenocarcinoma.This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.Esophageal CancerKEYTRUDA is indicated for the treatment of patients with locally advanced or metastatic esophageal or gastroesophageal (GEJ) (tumors with epicenter 1 to 5 centimeters above the GEJ) carcinoma that is not amenable to surgical resection or definitive chemoradiation either:
- in combination with platinum- and fluoropyrimidine-based chemotherapy, or
- as a single agent after one or more prior lines of systemic therapy for patients with tumors of squamous cell histology that express PD-L1 (CPS ≥10) as determined by an FDA-approved test.
Cervical CancerKEYTRUDA, in combination with chemotherapy, with or without bevacizumab, is indicated for the treatment of patients with persistent, recurrent, or metastatic cervical cancer whose tumors express PD-L1 (CPS ≥1) as determined by an FDA-approved test.KEYTRUDA, as a single agent, is indicated for the treatment of patients with recurrent or metastatic cervical cancer with disease progression on or after chemotherapy whose tumors express PD-L1 (CPS ≥1) as determined by an FDA-approved test.Hepatocellular CarcinomaKEYTRUDA is indicated for the treatment of patients with hepatocellular carcinoma (HCC) who have been previously treated with sorafenib. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.Merkel Cell CarcinomaKEYTRUDA is indicated for the treatment of adult and pediatric patients with recurrent locally advanced or metastatic Merkel cell carcinoma (MCC). This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.Renal Cell CarcinomaKEYTRUDA, in combination with axitinib, is indicated for the first-line treatment of adult patients with advanced renal cell carcinoma (RCC).KEYTRUDA is indicated for the adjuvant treatment of patients with RCC at intermediate-high or high risk of recurrence following nephrectomy, or following nephrectomy and resection of metastatic lesions.Tumor Mutational Burden-High CancerKEYTRUDA is indicated for the treatment of adult and pediatric patients with unresectable or metastatic tumor mutational burden-high (TMB-H) [≥10 mutations/megabase] solid tumors, as determined by an FDA-approved test, that have progressed following prior treatment and who have no satisfactory alternative treatment options. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials. The safety and effectiveness of KEYTRUDA in pediatric patients with TMB-H central nervous system cancers have not been established.Cutaneous Squamous Cell CarcinomaKEYTRUDA is indicated for the treatment of patients with recurrent or metastatic cutaneous squamous cell carcinoma (cSCC) or locally advanced cSCC that is not curable by surgery or radiation.Triple-Negative Breast CancerKEYTRUDA is indicated for the treatment of patients with high-risk early-stage triple-negative breast cancer (TNBC) in combination with chemotherapy as neoadjuvant treatment, and then continued as a single agent as adjuvant treatment after surgery.KEYTRUDA, in combination with chemotherapy, is indicated for the treatment of patients with locally recurrent unresectable or metastatic TNBC whose tumors express PD-L1 (CPS ≥10) as determined by an FDA-approved test.
For more information about our oncology clinical trials, visit www.merck.com/clinicaltrials. For more information, visit www.merck.com and connect with us on Twitter, Facebook, Instagram, YouTube and LinkedIn Please see Prescribing Information for KEYTRUDA (pembrolizumab) at http://www.merck.com/product/usa/pi_circulars/k/keytruda/keytruda_pi.pdf and Medication Guide for KEYTRUDA at http://www.merck.com/product/usa/pi_circulars/k/keytruda/keytruda_mg.pdf .Source: Merck & Co., Inc.
Merck says late-stage melanoma trial for Keytruda met main secondary goal
Mar. 07, 2022 7:02 AM ET
By: Dulan Lokuwithana, SA News Editor
- Updating results from its KEYNOTE-716 trial, Merck (NYSE:MRK) said on Monday that its blockbuster anti-PD-1 therapy, Keytruda met the key secondary endpoint of the trial among patients with resected stage IIB and IIC melanoma.
- https://seekingalpha.com/news/3810089-merck-says-late-stage-melanoma-trial-for-keytruda-met-main-secondary-goal
- https://seekingalpha.com/symbol/MRK
- https://www.keytruda.com/
Opdivo® (nivolumab) with Chemotherapy
Opdivo® (nivolumab) with Chemotherapy
Opdivo® (nivolumab) with Chemotherapy
U.S. Food and Drug Administration Approves Opdivo® (nivolumab) with Chemotherapy as Neoadjuvant Treatment for Certain Adult Patients with Resectable Non-Small Cell Lung Cancer
03/04/2022CATEGORY:
Approval marks the first-and-only immunotherapy-based treatment for use before surgery for non-small cell lung cancer1In the Phase 3 CheckMate -816 trial, Opdivo plus platinum-doublet chemotherapy significantly improved event-free survival and pathologic complete response compared to platinum-doublet chemotherapy alone1Opdivo-based combinations now approved in both metastatic and earlier stages of non-small cell lung cancerPRINCETON, N.J.--(BUSINESS WIRE)-- Bristol Myers Squibb (NYSE: BMY) today announced that the U.S. Food and Drug Administration (FDA) approved Opdivo®(nivolumab) 360 mg (injection for intravenous use) in combination with platinum-doublet chemotherapy every three weeks for three cycles for adult patients with resectable (tumors ≥4 cm or node positive) non-small cell lung cancer (NSCLC) in the neoadjuvant setting.1Opdivo plus chemotherapy is approved regardless of PD-L1 status.1 The approval is based on the CheckMate -816 trial, the first positive Phase 3 trial of an immunotherapy-based combination used before surgery for resectable NSCLC. The primary endpoints included event-free survival (EFS) and pathologic complete response (pCR), which were evaluated using independent blinded review, and an additional efficacy outcome measure was overall survival (OS).1 The study compared Opdivo plus platinum-doublet chemotherapy (n=179) to platinum-doublet chemotherapy alone (n=179).1In the trial, when given before surgery, Opdivoplus chemotherapy showed a statistically significant improvement in EFS with a 37% reduction in the risk of progression, recurrence or death (Hazard Ratio [HR] 0.63; 95% Confidence Interval [CI]: 0.45 to 0.87; P=0.0052) compared to chemotherapy alone.1Opdivo plus chemotherapy showed a median EFS of 31.6 months (95% CI: 30.2 to Not Reached [NR]) compared to 20.8 months for patients treated with chemotherapy alone (95% CI: 14.0 to 26.7).1Additionally, 24% of patients treated with Opdivo plus chemotherapy achieved pCR (95% CI: 18.0 to 31.0), compared to 2.2% of patients treated with chemotherapy alone (95% CI: 0.6 to 5.6; estimated treatment difference 21.6; 95% CI: 15.1 to 28.2; P<0.0001).1 A prespecified interim analysis for OS resulted in a HR of 0.57 (95% CI: 0.38 to 0.87), which did not cross the boundary for statistical significance.1“Given the rates of disease recurrence in patients with resectable NSCLC, additional treatment options are needed that can be given before surgery to help improve the chance of successful surgical treatment and support the goal of reducing the risk of cancer returning,” said Mark Awad, MD, PhD, CheckMate -816 study investigator and clinical director of the Lowe Center for Thoracic Oncology at Dana-Farber Cancer Institute.2,3 “The approval of nivolumab with platinum-doublet chemotherapy marks a turning point in how we treat resectable NSCLC and it enables us to use immunotherapy and chemotherapy as neoadjuvant treatment for patients before surgery. Today’s announcement reinforces the need to increase the rates of NSCLC screening and early detection, and for patients to discuss treatment options with their providers.”1Opdivo is associated with the following Warnings & Precautions: severe and fatal immune-mediated adverse reactions including pneumonitis, colitis, hepatitis and hepatotoxicity, endocrinopathies, dermatologic adverse reactions, nephritis with renal dysfunction, other immune-mediated adverse reactions; infusion-related reactions; complications of allogeneic hematopoietic stem cell transplantation (HSCT); embryo-fetal toxicity; and increased mortality in patients with multiple myeloma when Opdivo is added to a thalidomide analogue and dexamethasone, which is not recommended outside of controlled clinical trials.1 Please see Important Safety Information below.“At Bristol Myers Squibb, we are leading innovative science in the use of immunotherapy in earlier stages of cancer and are committed to bringing these options to patients,” said Adam Lenkowsky, senior vice president and general manager, U.S. Cardiovascular, Immunology and Oncology at Bristol Myers Squibb. “Today’s approval builds on that commitment and expands the role of Opdivo-based treatment in NSCLC, the most common form of lung cancer, so patients may benefit earlier in the course of their disease.”1,4This application was approved under the FDA’s Real-Time Oncology Review (RTOR) pilot program, which aims to ensure that safe and effective treatments are available to patients as early as possible.5 The review was also conducted under the FDA’s Project Orbis initiative, which enabled concurrent review by the health authorities in Australia, Canada and the United Kingdom, where the application remains under review. The EFS data from the Phase 3 CheckMate -816 trial will be presented at the American Association for Cancer Research Annual Meeting 2022 in April.
About CheckMate -816
CheckMate -816 is a randomized, open label trial evaluating Opdivo plus platinum-doublet chemotherapy compared to chemotherapy alone as neoadjuvant treatment in adult patients with resectable non-small cell lung cancer, regardless of PD-L1 expression.1 The trial included patients with histologically confirmed Stage IB (≥4 cm), II or IIIA NSCLC (per the 7th edition American Joint Committee on Cancer/Union for International Cancer Control [AJCC/UICC] staging criteria), ECOG performance status 0 or 1, and measurable disease (per RECIST version 1.1).1 Patients with unresectable or metastatic NSCLC, known EGFR mutations or ALK translocations, Grade 2 or greater peripheral neuropathy, active autoimmune disease, or medical conditions requiring systemic immunosuppression were excluded from the study.1 For the primary analysis, 358 patients were randomized to receive either Opdivo 360 mg plus histology-based platinum doublet chemotherapy on the same day every three weeks for up to three cycles, or platinum doublet chemotherapy every three weeks for up to three cycles, followed by surgery.1The primary endpoints of the trial were EFS determined by Blinded Independent Central Review (BICR) and pCR determined by Blinded Independent Pathology Review (BIPR).1 EFS is defined as the length of time from randomization to any of the following events: any progression of disease precluding surgery, progression, or recurrence of disease after surgery, or death due to any cause.1 In addition, pCR was defined as 0% residual viable tumor cells in both primary tumor and sampled lymph nodes as assessed by BIPR.1 Additional efficacy outcome measures included OS.1
INDICATIONS
OPDIVO® (nivolumab), in combination with platinum-doublet chemotherapy, is indicated as neoadjuvant treatment of adult patients with resectable (tumors ≥4 cm or node positive) non-small cell lung cancer (NSCLC).OPDIVO® (nivolumab) is indicated for the adjuvant treatment of adult patients with melanoma with involvement of lymph nodes or metastatic disease who have undergone complete resection.OPDIVO® (nivolumab), in combination with YERVOY® (ipilimumab), is indicated for the first-line treatment of adult patients with metastatic non-small cell lung cancer (NSCLC) whose tumors express PD-L1 (≥1%) as determined by an FDA-approved test, with no EGFR or ALK genomic tumor aberrations.OPDIVO® (nivolumab), in combination with YERVOY® (ipilimumab) and 2 cycles of platinum-doublet chemotherapy, is indicated for the first-line treatment of adult patients with metastatic or recurrent non-small cell lung cancer (NSCLC), with no EGFR or ALK genomic tumor aberrations.OPDIVO® (nivolumab), as a single agent, is indicated for the adjuvant treatment of adult patients with urothelial carcinoma (UC) who are at high risk of recurrence after undergoing radical resection of UC.OPDIVO® (nivolumab) is indicated for the adjuvant treatment of completely resected esophageal or gastroesophageal junction cancer with residual pathologic disease in adult patients who have received neoadjuvant chemoradiotherapy (CRT).
IMPORTANT SAFETY INFORMATION
https://www.opdivo.com/
Please see US Full Prescribing Information for OPDIVO and YERVOY.
For more information about Bristol Myers Squibb, visit us at BMS.com or follow us on LinkedIn, Twitter, YouTube, Facebook and Instagram. Celgene and Juno Therapeutics are wholly owned subsidiaries of Bristol-Myers Squibb Company. In certain countries outside the U.S., due to local laws, Celgene and Juno Therapeutics are referred to as, Celgene, a Bristol Myers Squibb company and Juno Therapeutics, a Bristol Myers Squibb company.
View source version on businesswire.com: https://www.businesswire.com/news/home/20220301006264/en/ Source: Bristol Myers Squibb
Bristol Myers Opdivo combo gets FDA nod for expanded use in lung cancer
Mar. 07, 2022 4:27 AM ET
Bristol-Myers Squibb Company (BMY)
By: Ravikash, SA News Editor1 Comment
- The U.S. Food and Drug Administration (FDA) approved Bristol Myers Squibb's (NYSE:BMY) Opdivo (nivolumab) in combination with platinum-doublet chemotherapy for adult patients with resectable non-small cell lung cancer (NSCLC) in the neoadjuvant setting (use before surgery).
- https://seekingalpha.com/news/3810049-bristol-myers-opdivo-combo-gets-fda-nod-for-expanded-use-in-lung-cancer
- https://seekingalpha.com/symbol/BMY
- https://www.bms.com/https://www.opdivo.com/
IMBRUVICA® (ibrutinib)
Opdivo® (nivolumab) with Chemotherapy
OPDIVO® (nivolumab) and YERVOY® (ipilimumab)
February 28, 2022
AbbVie Seeks New Indication for IMBRUVICA® (ibrutinib) in Pediatric Patients with Chronic Graft Versus Host Disease (cGVHD)
- cGVHD is a life-threatening and rare condition that currently does not have an approved treatment for children under 12 and can occur in patients after receiving peripheral blood or bone marrow stem cell transplantation
- If approved, IMBRUVICA would offer pediatric and adolescent patients the first BTKi treatment option with an oral suspension formulation to help manage their cGVHD after failure of one or more lines of systemic therapy
- The sNDA and NDA submissions were primarily based on results of three years of data from the Phase 1/2 iMAGINE clinical trial
- IMBRUVICA was the first treatment approved in the U.S. in 2017 for adult patients with cGVHD after failure of one or more lines of systemic therapy
NORTH CHICAGO, Ill., Feb. 28, 2022 /PRNewswire/ -- AbbVie (NYSE: ABBV), today announced the submission of a supplemental New Drug Application (sNDA) to the U.S. Food and Drug Administration (FDA) for IMBRUVICA® (ibrutinib) for the treatment of pediatric and adolescent patients one year and older with chronic graft versus host disease (cGVHD) after failure of one or more lines of systemic therapy. A New Drug Application (NDA) was also submitted for an oral suspension formulation of IMBRUVICA to provide an alternative administration option for pediatric patients. If approved, this represents AbbVie's first pediatric indication for IMBRUVICA.
cGVHD is a life-threatening complication for about 14,000 patients each year after receiving a donor stem cell or bone marrow transplantation.1,2 Nearly half of these transplant patients develop cGVHD, and there are currently no FDA-approved treatment options for children under 12.3 The applications seek to update the IMBRUVICA U.S. Prescribing Information primarily based on the analysis of three years of data from the Phase 1/2 iMAGINE clinical trial, including use of a new oral suspension formulation of the treatment.
"We are committed to this work with IMBRUVICA in the hopes of providing the first FDA-approved BTKi treatment option for younger patients with cGVHD, including a new oral suspension formulation," said James Dean, M.D., Ph.D., IMBRUVICA Global Development Lead and Executive Medical Director at AbbVie. "For young children, the availability of a liquid oral suspension versus an oral capsule or tablet can be significant to enable them to take the recommended dose and address challenges swallowing capsules or tablets."
The iMAGINE clinical trial enrolled 59 patients 1-19 years of age with relapsed/refractory (R/R) or new-onset moderate/severe cGVHD. The primary endpoints of the study were pharmacokinetics (PK) and safety; secondary endpoints included overall response rate. Results showed an overall response rate of 78 percent with IMBRUVICA and that PK data was consistent with adult dosing of IMBRUVICA. After 20 weeks, sustained response rates were observed in 70 percent and 58 percent of treatment-naive and R/R responders, respectively. Safety was consistent with the established profile for IMBRUVICA, with observed adverse events (AEs) consistent with those observed in adult patients with moderate to severe cGVHD. The most common Grade ≥3 AEs (≥ 5% of subjects) overall were pyrexia (8.5%), neutropenia (6.8%), stomatitis (6.8%), hypoxia (6.8%), osteonecrosis (6.8%), alanine aminotransferase increased (5.1%), hypokalemia (5.1%), and pneumothorax (5.1%).
"It is important to empower patients and their families with evidence-based knowledge and I am encouraged by the results from the iMAGINE clinical trial of IMBRUVICA," said Dr. Paul A. Carpenter, attending physician at Seattle Children's Hospital and study principal investigator. "Results show that PK and safety were consistent with the known profile of IMBRUVICA and that of cGVHD. Efficacy results, including sustained response rates, were also encouraging."
In 2017, IMBRUVICA was first approved as a single-agent therapy for adult patients with cGVHD who have experienced failure of prior systemic therapy, becoming the first FDA-approved treatment for adults with cGVHD. IMBRUVICA could be the first FDA-approved BTKi treatment option for pediatric and adolescent patients with cGVHD.
About cGVHD
cGVHD occurs when donated peripheral blood or bone marrow stem cells view the recipient's body as foreign and the donated cells launch an immune attack on the body.4 cGVHD impacts major organs, with the skin, eyes, mouth and liver being most common.5 About 35 percent of the estimated 8,000 patients who undergo life-saving allogeneic Hematopoietic Stem Cell Transplant (HSCT) per year develop cGVHD that requires systemic treatment.4 Additionally, cGVHD is the most common cause of morbidity after allogeneic transplant.6 Steroids are the current standard treatment for pediatric cGVHD.7
About the iMAGINE Study
iMAGINE (PCYC-1146-IM) is an interventional single group treatment Phase 1/2 study, which enrolled 59 pediatric patients with chronic graft versus host disease (cGVHD). In the two-part study, Part A patients ages one to <12 years with moderate or severe cGVHD after failure of one or more lines of systemic therapy received IMBRUVICA oral suspension or capsule starting at 120mg/m2 once daily. To determine the Recommended Pediatric Equivalent Dose (RPED), dosage was escalated to 240mg/m2 after 14 days if no Grade 3 or higher related toxicity was observed. In Part B, patients 12 to <22 years of age with moderate or severe cGVHD who were newly diagnosed or had failed one or more lines of systemic therapy were given 420mg IMBRUVICA orally once daily. Once the RPED was determined in Part A, patients 1 to <12 years of age with new-onset or relapsed/refractory cGVHD could be enrolled in Part B. Primary endpoints included pharmacokinetics (PK) and safety, and secondary endpoints included overall response rate (ORR; CR/PR) per 2014 NIH criteria, overall survival, duration of response (DOR), and patient reported outcomes.
About IMBRUVICA
IMBRUVICA® (ibrutinib) is a once-daily oral medication that is jointly developed and commercialized by Pharmacyclics LLC, an AbbVie Company and Janssen Biotech, Inc. IMBRUVICA® blocks the Bruton's tyrosine kinase (BTK) protein, which is needed by normal and abnormal B cells, to multiply and spread. By blocking BTK, IMBRUVICA may help move abnormal B cells out of their nourishing environments in the lymph nodes, bone marrow, and other organs.8,9,10
IMBRUVICA® is approved in more than 100 countries and has been used to treat more than 250,000 patients worldwide. There are more than 50 company-sponsored clinical trials, including 18 ongoing or completed Phase 3 studies, over 11 years evaluating the efficacy and safety of IMBRUVICA®.
IMBRUVICA® was first approved by the U.S. Food and Drug Administration (FDA) in November 2013, and today is indicated for adult patients in six disease areas, including five hematologic cancers. These include adults with CLL/small lymphocytic lymphoma (SLL) with or without 17p deletion (del17p) and adults with Waldenström's macroglobulinemia (WM), as well as adult patients with previously treated mantle cell lymphoma (MCL)*, adult patients with previously treated marginal zone lymphoma (MZL) who require systemic therapy and have received at least one prior anti-CD20-based therapy*, as well as adult patients with previously treated chronic graft-versus-host disease (cGVHD) after failure of one or more lines of systemic therapy.11
*Accelerated approval was granted for MCL and MZL based on overall response rate. Continued approval for MCL and MZL may be contingent upon verification and description of clinical benefit in confirmatory trials.
Since 2019, the National Comprehensive Cancer Network® (NCCN®), recommends ibrutinib (IMBRUVICA®) as a preferred regimen for first-line treatment of CLL/SLL, with Category 1 status for previously untreated patients without del17p. Additionally, IMBRUVICA® is a preferred treatment regimen for previously untreated patients with del17p. Since January 2020, the NCCN Guidelines recommend IMBRUVICA® as a category 2A preferred regimen for the treatment of relapsed/refractory MCL. Since September 2020, the NCCN Guidelines recommend IMBRUVICA® with or without rituximab as a Category 1 preferred regimen for both untreated and previously treated WM patients.12
For more information, visit www.IMBRUVICA.com.
Uses
What is IMBRUVICA® (ibrutinib)?
IMBRUVICA® (ibrutinib) is a prescription medicine used to treat adults with:
- Mantle cell lymphoma (MCL) who have received at least one prior treatment
- Chronic lymphocytic leukemia (CLL)/Small lymphocytic lymphoma (SLL)
- Chronic lymphocytic leukemia (CLL)/Small lymphocytic lymphoma (SLL) with 17p deletion
- Waldenström's macroglobulinemia (WM)
- Marginal zone lymphoma (MZL) who require a medicine by mouth or injection (systemic therapy) and have received a certain type of prior treatment
- Chronic graft versus host disease (cGVHD) after failure of 1 or more lines of systemic therapy
It is not known if IMBRUVICA® is safe and effective in children.
Please see the full Important Product Information.
About AbbVie in Oncology
At AbbVie, we are committed to transforming standards of care for multiple blood cancers while advancing a dynamic pipeline of investigational therapies across a range of cancer types. Our dedicated and experienced team joins forces with innovative partners to accelerate the delivery of potentially breakthrough medicines. We are evaluating more than 20 investigational medicines in over 300 clinical trials across some of the world's most widespread and debilitating cancers. As we work to have a remarkable impact on people's lives, we are committed to exploring solutions to help patients obtain access to our cancer medicines. For more information, please visit http://www.abbvie.com/oncology.
For more information about AbbVie, please visit us at www.abbvie.com. Follow @abbvie on Twitter, Facebook, Instagram, YouTube and LinkedIn.
AbbVie submits sNDA for Imbruvica in pediatric indication
Feb. 28, 2022 9:29 AM ET
By: Jonathan Block, SA News Editor2 Comments
- AbbVie (NYSE:ABBV) has submitted a supplemental New Drug Application (sNDA) for Imbruvica (ibrutinib) to the FDA as a second-line therapy for chronic graft versus host disease (cGVHD) for children one year and older.
- https://seekingalpha.com/news/3806885-abbvie-submits-snda-for-imbruvica-in-pediatric-indication
- https://seekingalpha.com/symbol/ABBV
- https://www.imbruvica.com/
- https://www.abbvie.com/
OPDIVO® (nivolumab) and YERVOY® (ipilimumab)
KEYTRUDA® (pembrolizumab) Plus LENVIMA® (lenvatinib)
OPDIVO® (nivolumab) and YERVOY® (ipilimumab)
Bristol Myers Squibb Receives Positive CHMP Opinion Recommending Approval for Opdivo (nivolumab) plus Yervoy (ipilimumab) for First-Line Treatment of Patients with Unresectable Advanced, Recurrent or Metastatic Esophageal Squamous Cell Carcinoma...
02/25/2022CATEGORY:
Recommendation based on results from the Phase 3 CheckMate -648 trial, in which the immunotherapy combination demonstrated significantly improved overall survival compared to fluoropyrimidine- and platinum-containing chemotherapyOpdivo plus Yervoy is the first immunotherapy combination to show a superior survival benefit versus chemotherapy in this settingPRINCETON, N.J.--(BUSINESS WIRE)--Bristol Myers Squibb (NYSE:BMY):Bristol Myers Squibb Receives Positive CHMP Opinion Recommending Approval for Opdivo (nivolumab) plus Yervoy (ipilimumab) for First-Line Treatment of Patients with Unresectable Advanced, Recurrent or Metastatic Esophageal Squamous Cell Carcinoma with Tumor Cell PD-L1 Expression ≥ 1%Bristol Myers Squibb (NYSE: BMY) today announced that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has recommended approval of Opdivo (nivolumab) plus Yervoy (ipilimumab) for the first-line treatment of adults with unresectable advanced, recurrent or metastatic esophageal squamous cell carcinoma (ESCC) with tumor cell PD-L1 expression ≥ 1%. The European Commission (EC), which has the authority to approve medicines for the European Union (EU), will now review the CHMP opinion.“Currently, the median overall survival for advanced ESCC patients is around ten months with standard chemotherapy,” said Ian M. Waxman, M.D., development lead, gastrointestinal cancers, Bristol Myers Squibb. “The CHMP’s positive recommendation for Opdivo plus Yervoy as a first-line treatment option for patients with unresectable advanced, recurrent or metastatic ESCC with tumor cell PD-L1 expression ≥1% marks an important step forward for patients in the EU awaiting new therapeutic options for their disease.”The positive opinion is based on results from the Phase 3 CheckMate -648 trial, which showed that treatment with Opdivo plus Yervoy demonstrated a statistically significant and clinically meaningful overall survival (OS) benefit compared to fluoropyrimidine- and platinum-containing chemotherapy at the pre-specified interim analysis in patients with unresectable advanced, recurrent or metastatic ESCC with tumor cell PD-L1 expression ≥1% (median, 13.7 months vs 9.1 months, HR = 0.64; 98.6% CI: 0.46 to 0.90; p-value = 0.001). The safety profile of Opdivo plus Yervoy was consistent with previously reported studies. Results from CheckMate -648 were presented at the American Society of Clinical Oncology (ASCO) Annual Meeting in June 2021.Bristol Myers Squibb thanks the patients and investigators involved in the CheckMate -648 trial.
About CheckMate -648CheckMate -648 is a randomized Phase 3 study evaluating Opdivo plus Yervoy (N=325) or Opdivo plus fluorouracil and cisplatin (N=321) against fluorouracil plus cisplatin alone (N=324) in patients with previously untreated, unresectable advanced, recurrent or metastatic esophageal squamous cell carcinoma.The primary endpoints of the trial are overall survival (OS) and progression-free survival (PFS) by blinded independent central review (BICR) in patients with tumor cell PD-L1 expression ≥1% for both Opdivo-based combinations versus chemotherapy. Secondary endpoints of the trial include OS and PFS by BICR in the all-randomized population.In the Opdivo plus chemotherapy arm, patients received treatment with Opdivo 240 mg on Day 1 and Day 15, fluorouracil 800 mg/m²/day on Day 1 through Day 5 (for 5 days), and cisplatin 80 mg/m² on Day 1 of four-week cycle. Patients received Opdivo for up to 24 months or until disease progression, unacceptable toxicity or withdrawal of consent, and chemotherapy until disease progression, unacceptable toxicity or withdrawal of consent.In the Opdivo plus Yervoy arm, patients received treatment with Opdivo 3 mg/kg every 2 weeks and Yervoy 1 mg/kg every 6 weeks up to 24 months or until disease progression, unacceptable toxicity or withdrawal of consent.
About OpdivoOpdivo is a programmed death-1 (PD-1) immune checkpoint inhibitor that is designed to uniquely harness the body’s own immune system to help restore anti-tumor immune response. By harnessing the body’s own immune system to fight cancer, Opdivo has become an important treatment option across multiple cancers.Opdivo’s leading global development program is based on Bristol Myers Squibb’s scientific expertise in the field of Immuno-Oncology and includes a broad range of clinical trials across all phases, including Phase 3, in a variety of tumor types. To date, the Opdivo clinical development program has treated more than 35,000 patients. The Opdivo trials have contributed to gaining a deeper understanding of the potential role of biomarkers in patient care, particularly regarding how patients may benefit from Opdivo across the continuum of PD-L1 expression.In July 2014, Opdivo was the first PD-1 immune checkpoint inhibitor to receive regulatory approval anywhere in the world. Opdivo is currently approved in more than 65 countries, including the United States, the European Union, Japan and China. In October 2015, the Company’s Opdivo and Yervoy combination regimen was the first Immuno-Oncology combination to receive regulatory approval for the treatment of metastatic melanoma and is currently approved in more than 50 countries, including the United States and the European Union.
INDICATIONSOPDIVO® (nivolumab), as a single agent, is indicated for the treatment of patients with unresectable or metastatic melanoma.OPDIVO® (nivolumab), in combination with YERVOY® (ipilimumab), is indicated for the treatment of patients with unresectable or metastatic melanoma.OPDIVO® (nivolumab) is indicated for the adjuvant treatment of patients with melanoma with involvement of lymph nodes or metastatic disease who have undergone complete resection.OPDIVO® (nivolumab), in combination with YERVOY® (ipilimumab), is indicated for the first-line treatment of adult patients with metastatic non-small cell lung cancer (NSCLC) whose tumors express PD-L1 (≥1%) as determined by an FDA-approved test, with no EGFR or ALK genomic tumor aberrations.OPDIVO® (nivolumab), in combination with YERVOY® (ipilimumab) and 2 cycles of platinum-doublet chemotherapy, is indicated for the first-line treatment of adult patients with metastatic or recurrent non-small cell lung cancer (NSCLC), with no EGFR or ALK genomic tumor aberrations.OPDIVO® (nivolumab) is indicated for the treatment of patients with metastatic non-small cell lung cancer (NSCLC) with progression on or after platinum-based chemotherapy. Patients with EGFR or ALK genomic tumor aberrations should have disease progression on FDA-approved therapy for these aberrations prior to receiving OPDIVO.OPDIVO® (nivolumab), in combination with YERVOY® (ipilimumab), is indicated for the first-line treatment of adult patients with unresectable malignant pleural mesothelioma (MPM).OPDIVO® (nivolumab), in combination with YERVOY® (ipilimumab), is indicated for the first-line treatment of patients with intermediate or poor risk advanced renal cell carcinoma (RCC).OPDIVO® (nivolumab), in combination with cabozantinib, is indicated for the first-line treatment of patients with advanced renal cell carcinoma (RCC).OPDIVO® (nivolumab) is indicated for the treatment of patients with advanced renal cell carcinoma (RCC) who have received prior anti-angiogenic therapy.OPDIVO® (nivolumab) is indicated for the treatment of adult patients with classical Hodgkin lymphoma (cHL) that has relapsed or progressed after autologous hematopoietic stem cell transplantation (HSCT) and brentuximab vedotin or after 3 or more lines of systemic therapy that includes autologous HSCT. This indication is approved under accelerated approval based on overall response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.OPDIVO® (nivolumab) is indicated for the treatment of patients with recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN) with disease progression on or after platinum-based therapy.OPDIVO® (nivolumab) is indicated for the treatment of patients with locally advanced or metastatic urothelial carcinoma who have disease progression during or following platinum-containing chemotherapy or have disease progression within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy.OPDIVO® (nivolumab), as a single agent, is indicated for the adjuvant treatment of patients with urothelial carcinoma (UC) who are at high risk of recurrence after undergoing radical resection of UC.OPDIVO® (nivolumab), as a single agent, is indicated for the treatment of adult and pediatric (12 years and older) patients with microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) metastatic colorectal cancer (CRC) that has progressed following treatment with a fluoropyrimidine, oxaliplatin, and irinotecan. This indication is approved under accelerated approval based on overall response rate and duration of response.Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.OPDIVO® (nivolumab), in combination with YERVOY® (ipilimumab), is indicated for the treatment of adults and pediatric patients 12 years and older with microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) metastatic colorectal cancer (CRC) that has progressed following treatment with a fluoropyrimidine, oxaliplatin, and irinotecan. This indication is approved under accelerated approval based on overall response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.OPDIVO® (nivolumab), in combination with YERVOY® (ipilimumab), is indicated for the treatment of patients with hepatocellular carcinoma (HCC) who have been previously treated with sorafenib. This indication is approved under accelerated approval based on overall response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.OPDIVO® (nivolumab) is indicated for the treatment of patients with unresectable advanced, recurrent or metastatic esophageal squamous cell carcinoma (ESCC) after prior fluoropyrimidine- and platinum-based chemotherapy.OPDIVO® (nivolumab) is indicated for the adjuvant treatment of completely resected esophageal or gastroesophageal junction cancer with residual pathologic disease in patients who have received neoadjuvant chemoradiotherapy (CRT).OPDIVO® (nivolumab), in combination with fluoropyrimidine- and platinum- containing chemotherapy, is indicated for the treatment of patients with advanced or metastatic gastric cancer, gastroesophageal junction cancer, and esophageal adenocarcinoma.
For more information about Bristol Myers Squibb, visit us at BMS.com or follow us on LinkedIn, Twitter, YouTube, Facebook and Instagram. View source version on businesswire.com: https://www.businesswire.com/news/home/20220224006058/en/Bristol Myers Squibb Source: Bristol Myers Squibb
Bristol Myers Opdivo gets EMA panel nod for use as adjuvant therapy in urothelial cancer
Feb. 25, 2022 7:44 AM ET
Bristol-Myers Squibb Company (BMY)
By: Ravikash, SA News Editor
- Bristol Myers Squibb (NYSE:BMY) said a committee of the European Medicines Agency (EMA) recommended approval of Opdivo (nivolumab) for the adjuvant treatment of adults with muscle-invasive urothelial carcinoma with tumor cell PD-L1 expression ≥1% who are at a high risk of recurrence after undergoing surgery.
- https://seekingalpha.com/news/3805853-bristol-myers-opdivo-gets-ema-panel-nod-for-use-as-adjuvant-therapy-in-urothelial-cancer
- https://seekingalpha.com/symbol/BMY
- https://www.opdivo.com/about-opdivo/how-the-combination-works-combinationtherapy#:~:text=(advanced%20melanoma).-,OPDIVO%C2%AE%20(nivolumab)%20is%20a%20prescription%20medicine%20used%20in%20combination,than%2018%20years%20of%20age.
02/25/2022
02/25/2022
02/25/2022
KEYTRUDA® (pembrolizumab) Plus LENVIMA® (lenvatinib)
KEYTRUDA® (pembrolizumab) Plus LENVIMA® (lenvatinib)
KEYTRUDA® (pembrolizumab) Plus LENVIMA® (lenvatinib)
KEYTRUDA® (pembrolizumab) Plus LENVIMA® (lenvatinib) Approved in Japan for Radically Unresectable or Metastatic Renal Cell Carcinoma
February 25, 2022 6:45 am ET
Results From CLEAR/KEYNOTE-581 Showed KEYTRUDA Plus LENVIMA Significantly Reduced the Risk of Disease Progression or Death by 61%, With a Median Progression-Free Survival of Nearly Two Years Versus Nine Months for Sunitinib
KEYTRUDA Plus LENVIMA Now Approved in Japan for Two Types of Cancer
KENILWORTH, N.J. & TOKYO--(BUSINESS WIRE)-- Merck (NYSE: MRK), known as MSD outside the United States and Canada, and Eisai today announced that the Japanese Ministry of Health, Labour and Welfare (MHLW) has approved the combination of KEYTRUDA, Merck’s anti-PD-1 therapy, plus LENVIMA, the orally available multiple receptor tyrosine kinase inhibitor discovered by Eisai, for radically unresectable or metastatic renal cell carcinoma (RCC). KEYTRUDA plus LENVIMA is also approved in the U.S. and Europe for the first-line treatment of adult patients with advanced RCC. This marks the second approval of this combination in Japan; in December 2021, KEYTRUDA plus LENVIMA was approved for unresectable, advanced or recurrent endometrial carcinoma that progressed after chemotherapy.
The approval is based on results from the pivotal Phase 3 CLEAR (Study 307)/KEYNOTE-581 trial, in which KEYTRUDA plus LENVIMA demonstrated statistically significant improvements versus sunitinib in the primary efficacy outcome of progression-free survival (PFS). Results showed KEYTRUDA plus LENVIMA (n=355) reduced the risk of disease progression or death by 61% (HR=0.39 [95% CI, 0.32-0.49]; p<0.0001), with a median PFS of 23.9 months versus 9.2 months for sunitinib (n=357).
“Nearly one in three cases of renal cell carcinoma are diagnosed at an advanced stage, and patients are in need of new treatment options that may improve survival outcomes,” said Dr. Gregory Lubiniecki, Vice President, Oncology Clinical Research, Merck Research Laboratories. “In the CLEAR/KEYNOTE-581 trial, KEYTRUDA plus LENVIMA reduced the risk of disease progression or death by 61% versus sunitinib, a current standard of care. We are encouraged that patients with certain types of advanced renal cell carcinoma may have the opportunity to benefit from this combination.”
“Today’s milestone for KEYTRUDA plus LENVIMA as a treatment for radically unresectable or metastatic renal cell carcinoma is particularly exciting as it marks the second approval for the combination in Japan,” said Terushige Iike, President of Eisai Japan, Senior Vice President, Eisai. “We are thrilled to be able to provide Japanese patients with a new treatment option, illustrating our shared commitment with Merck to develop therapies with the aim of addressing the unmet needs of those living with difficult-to-treat cancers. We would like to thank the patients, families and healthcare providers who made this approval possible.”
The Japanese package inserts for KEYTRUDA and LENVIMA note that in the CLEAR/KEYNOTE-581 trial, adverse reactions were observed in 341 (96.9%) of 352 patients (including 42 of 42 Japanese patients) in the safety analysis set. The most common adverse reactions observed in 20% or more of patients included diarrhea in 192 patients (54.5%), hypertension in 184 patients (52.3%), hypothyroidism in 150 patients (42.6%), decreased appetite in 123 patients (34.9%), fatigue in 113 patients (32.1%), stomatitis in 113 patients (32.1%), palmar-plantar erythrodysesthesia syndrome in 99 patients (28.1%), proteinuria in 97 patients (27.6%), nausea in 94 patients (26.7%), dysphonia in 87 patients (24.7%), rash in 77 patients (21.9%), and asthenia in 71 patients (20.2%).
Renal cell carcinoma is the most common type of kidney cancer worldwide; about nine out of 10 kidney cancer diagnoses are RCC. In Japan, there were more than 25,000 new cases of kidney cancer diagnosed and more than 8,000 deaths from the disease in 2020. In the U.S., approximately 30% of patients with RCC will have metastatic disease at diagnosis. Survival is highly dependent on the stage at diagnosis, and with a five-year survival rate in the U.S. of 14% for patients diagnosed with metastatic disease, the prognosis for these patients is poor.
Merck and Eisai continue to study the KEYTRUDA plus LENVIMA combination across several types of cancer with more than 20 clinical trials.
About CLEAR/KEYNOTE-581 Trial
The approval is based on data from CLEAR (Study 307)/KEYNOTE-581 (ClinicalTrials.gov, NCT02811861), a Phase 3, multicenter, open-label, randomized trial conducted in 1,069 patients with advanced RCC in the first-line setting. The primary efficacy outcome was PFS as assessed by blinded independent central review (BICR) according to RECIST v1.1. Key secondary efficacy outcome measures were overall survival and objective response rate.
Patients were randomized 1:1:1 to receive KEYTRUDA (200 mg intravenously every three weeks for up to 24 months) plus LENVIMA (20 mg orally once daily), or LENVIMA (18 mg orally once daily) plus everolimus (5 mg orally once daily), or sunitinib (50 mg orally once daily for four weeks on treatment, followed by two weeks off treatment). Treatment continued until unacceptable toxicity or disease progression as determined by investigator and confirmed by BICR using RECIST v1.1. If disease progression was observed by imaging evaluation, clinically stable patients with no symptoms indicating disease progression were allowed to continue on study treatment until disease progression was observed in a subsequent imaging evaluation.
About KEYTRUDA® (pembrolizumab) Injection, 100 mg
KEYTRUDA is an anti-programmed death receptor-1 (PD-1) therapy that works by increasing the ability of the body’s immune system to help detect and fight tumor cells. KEYTRUDA is a humanized monoclonal antibody that blocks the interaction between PD-1 and its ligands, PD-L1 and PD-L2, thereby activating T lymphocytes which may affect both tumor cells and healthy cells.
Merck has the industry’s largest immuno-oncology clinical research program. There are currently more than 1,700 trials studying KEYTRUDA across a wide variety of cancers and treatment settings. The KEYTRUDA clinical program seeks to understand the role of KEYTRUDA across cancers and the factors that may predict a patient's likelihood of benefitting from treatment with KEYTRUDA, including exploring several different biomarkers.
Selected KEYTRUDA® (pembrolizumab) Indications in the U.S.
Melanoma
KEYTRUDA is indicated for the treatment of patients with unresectable or metastatic melanoma.
KEYTRUDA is indicated for the adjuvant treatment of adult and pediatric (12 years and older) patients with stage IIB, IIC, or III melanoma following complete resection.
Non-Small Cell Lung Cancer
KEYTRUDA, in combination with pemetrexed and platinum chemotherapy, is indicated for the first-line treatment of patients with metastatic nonsquamous non-small cell lung cancer (NSCLC), with no EGFR or ALK genomic tumor aberrations.
KEYTRUDA, in combination with carboplatin and either paclitaxel or paclitaxel protein-bound, is indicated for the first-line treatment of patients with metastatic squamous NSCLC.
KEYTRUDA, as a single agent, is indicated for the first-line treatment of patients with NSCLC expressing PD-L1 [tumor proportion score (TPS) ≥1%] as determined by an FDA-approved test, with no EGFR or ALK genomic tumor aberrations, and is:
- stage III where patients are not candidates for surgical resection or definitive chemoradiation, or
- metastatic.
KEYTRUDA, as a single agent, is indicated for the treatment of patients with metastatic NSCLC whose tumors express PD-L1 (TPS ≥1%) as determined by an FDA-approved test, with disease progression on or after platinum-containing chemotherapy. Patients with EGFR or ALK genomic tumor aberrations should have disease progression on FDA-approved therapy for these aberrations prior to receiving KEYTRUDA.
Head and Neck Squamous Cell Cancer
KEYTRUDA, in combination with platinum and fluorouracil (FU), is indicated for the first-line treatment of patients with metastatic or with unresectable, recurrent head and neck squamous cell carcinoma (HNSCC).
KEYTRUDA, as a single agent, is indicated for the first-line treatment of patients with metastatic or with unresectable, recurrent HNSCC whose tumors express PD-L1 [combined positive score (CPS ≥1)] as determined by an FDA-approved test.
KEYTRUDA, as a single agent, is indicated for the treatment of patients with recurrent or metastatic HNSCC with disease progression on or after platinum-containing chemotherapy.
Classical Hodgkin Lymphoma
KEYTRUDA is indicated for the treatment of adult patients with relapsed or refractory classical Hodgkin lymphoma (cHL).
KEYTRUDA is indicated for the treatment of pediatric patients with refractory cHL, or cHL that has relapsed after 2 or more lines of therapy.
Primary Mediastinal Large B-Cell Lymphoma
KEYTRUDA is indicated for the treatment of adult and pediatric patients with refractory primary mediastinal large B-cell lymphoma (PMBCL), or who have relapsed after 2 or more prior lines of therapy. KEYTRUDA is not recommended for treatment of patients with PMBCL who require urgent cytoreductive therapy.
Urothelial Carcinoma
KEYTRUDA is indicated for the treatment of patients with locally advanced or metastatic urothelial carcinoma (mUC):
- who are not eligible for any platinum-containing chemotherapy, or
- who have disease progression during or following platinum-containing chemotherapy or within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy.
Non-muscle Invasive Bladder Cancer
KEYTRUDA is indicated for the treatment of patients with Bacillus Calmette-Guerin (BCG)-unresponsive, high-risk, non-muscle invasive bladder cancer (NMIBC) with carcinoma in situ (CIS) with or without papillary tumors who are ineligible for or have elected not to undergo cystectomy.
Microsatellite Instability-High or Mismatch Repair Deficient Cancer
KEYTRUDA is indicated for the treatment of adult and pediatric patients with unresectable or metastatic microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) solid tumors that have progressed following prior treatment and who have no satisfactory alternative treatment options.
This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials. The safety and effectiveness of KEYTRUDA in pediatric patients with MSI-H central nervous system cancers have not been established.
Microsatellite Instability-High or Mismatch Repair Deficient Colorectal Cancer
KEYTRUDA is indicated for the treatment of patients with unresectable or metastatic MSI-H or dMMR colorectal cancer (CRC).
Gastric Cancer
KEYTRUDA, in combination with trastuzumab, fluoropyrimidine- and platinum-containing chemotherapy, is indicated for the first-line treatment of patients with locally advanced unresectable or metastatic HER2-positive gastric or gastroesophageal junction (GEJ) adenocarcinoma.
This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.
Esophageal Cancer
KEYTRUDA is indicated for the treatment of patients with locally advanced or metastatic esophageal or GEJ (tumors with epicenter 1 to 5 centimeters above the GEJ) carcinoma that is not amenable to surgical resection or definitive chemoradiation either:
- in combination with platinum- and fluoropyrimidine-based chemotherapy, or
- as a single agent after one or more prior lines of systemic therapy for patients with tumors of squamous cell histology that express PD-L1 (CPS ≥10) as determined by an FDA-approved test.
Cervical Cancer
KEYTRUDA, in combination with chemotherapy, with or without bevacizumab, is indicated for the treatment of patients with persistent, recurrent, or metastatic cervical cancer whose tumors express PD-L1 (CPS ≥1) as determined by an FDA-approved test.
KEYTRUDA, as a single agent, is indicated for the treatment of patients with recurrent or metastatic cervical cancer with disease progression on or after chemotherapy whose tumors express PD-L1 (CPS ≥1) as determined by an FDA-approved test.
Hepatocellular Carcinoma
KEYTRUDA is indicated for the treatment of patients with hepatocellular carcinoma (HCC) who have been previously treated with sorafenib. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.
Merkel Cell Carcinoma
KEYTRUDA is indicated for the treatment of adult and pediatric patients with recurrent locally advanced or metastatic Merkel cell carcinoma (MCC). This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.
Renal Cell Carcinoma
KEYTRUDA, in combination with axitinib, is indicated for the first-line treatment of adult patients with advanced renal cell carcinoma (RCC).
KEYTRUDA, in combination with LENVIMA, is indicated for the first-line treatment of adult patients with advanced RCC.
KEYTRUDA is indicated for the adjuvant treatment of patients with renal cell carcinoma (RCC) at intermediate-high or high risk of recurrence following nephrectomy, or following nephrectomy and resection of metastatic lesions.
Endometrial Carcinoma
KEYTRUDA, in combination with LENVIMA, is indicated for the treatment of patients with advanced endometrial carcinoma that is not MSI-H or dMMR, who have disease progression following prior systemic therapy in any setting and are not candidates for curative surgery or radiation.
Tumor Mutational Burden-High Cancer
KEYTRUDA is indicated for the treatment of adult and pediatric patients with unresectable or metastatic tumor mutational burden-high (TMB-H) [≥10 mutations/megabase] solid tumors, as determined by an FDA-approved test, that have progressed following prior treatment and who have no satisfactory alternative treatment options. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials. The safety and effectiveness of KEYTRUDA in pediatric patients with TMB-H central nervous system cancers have not been established.
Cutaneous Squamous Cell Carcinoma
KEYTRUDA is indicated for the treatment of patients with recurrent or metastatic cutaneous squamous cell carcinoma (cSCC) or locally advanced cSCC that is not curable by surgery or radiation.
Triple-Negative Breast Cancer
KEYTRUDA is indicated for the treatment of patients with high-risk early-stage triple-negative breast cancer (TNBC) in combination with chemotherapy as neoadjuvant treatment, and then continued as a single agent as adjuvant treatment after surgery.
KEYTRUDA, in combination with chemotherapy, is indicated for the treatment of patients with locally recurrent unresectable or metastatic TNBC whose tumors express PD-L1 (CPS ≥10) as determined by an FDA-approved test.
Please see Prescribing Information for KEYTRUDA (pembrolizumab) at http://www.merck.com/product/usa/pi_circulars/k/keytruda/keytruda_pi.pdf and Medication Guide for KEYTRUDA at http://www.merck.com/product/usa/pi_circulars/k/keytruda/keytruda_mg.pdf.
About LENVIMA® (lenvatinib); available as 10 mg and 4 mg capsules
LENVIMA, discovered and developed by Eisai, is a multiple receptor tyrosine kinase inhibitor that inhibits the kinase activities of vascular endothelial growth factor (VEGF) receptors VEGFR1 (FLT1), VEGFR2 (KDR), and VEGFR3 (FLT4). LENVIMA inhibits other kinases that have been implicated in pathogenic angiogenesis, tumor growth, and cancer progression in addition to their normal cellular functions, including fibroblast growth factor (FGF) receptors FGFR1-4, the platelet derived growth factor receptor alpha (PDGFRα), KIT, and RET. The combination of LENVIMA and everolimus showed increased anti-angiogenic and anti-tumor activity as demonstrated by decreased human endothelial cell proliferation, tube formation, and VEGF signaling in vitro and tumor volume in mouse xenograft models of human renal cell cancer greater than each drug alone. In syngeneic mouse tumor models, the combination of lenvatinib with an anti-PD-1 monoclonal antibody decreased tumor-associated macrophages, increased activated cytotoxic T cells, and demonstrated greater antitumor activity compared to either treatment alone.
LENVIMA® (lenvatinib) Indications in the U.S.
- For the treatment of patients with locally recurrent or metastatic, progressive, radioactive iodine-refractory differentiated thyroid cancer (DTC)
- In combination with KEYTRUDA, for the first-line treatment of adult patients with advanced renal cell carcinoma (RCC)
- In combination with everolimus, for the treatment of adult patients with advanced renal cell carcinoma (RCC) following one prior anti-angiogenic therapy
- For the first-line treatment of patients with unresectable hepatocellular carcinoma (HCC)
- In combination with KEYTRUDA, for the treatment of patients with advanced endometrial carcinoma (EC) that is not microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR), who have disease progression following prior systemic therapy in any setting and are not candidates for curative surgery or radiation.
Please see Prescribing Information for LENVIMA (lenvatinib) at http://www.lenvima.com/pdfs/prescribing-information.pdf .
About the Merck and Eisai Strategic Collaboration
In March 2018, Eisai and Merck, known as MSD outside the United States and Canada, through an affiliate, entered into a strategic collaboration for the worldwide co-development and co-commercialization of LENVIMA. Under the agreement, the companies will jointly develop, manufacture and commercialize LENVIMA, both as monotherapy and in combination with Merck’s anti-PD-1 therapy KEYTRUDA.
In addition to ongoing clinical studies evaluating the KEYTRUDA plus LENVIMA combination across several different tumor types, the companies have jointly initiated new clinical studies through the LEAP (LEnvatinib And Pembrolizumab) clinical program and are evaluating the combination in more than 10 different tumor types across more than 20 clinical trials.
For more information, visit www.merck.com and connect with us on Twitter, Facebook, Instagram, YouTube and LinkedIn.
For more information about Eisai, please visit www.eisai.com (for global headquarters: Eisai Co., Ltd.), us.eisai.com (for U.S. headquarters: Eisai Inc.) or www.eisai.eu (for Europe, Middle East, Africa, Russia, Australia, and New Zealand headquarters: Eisai Europe Ltd.), and connect with us on Twitter (U.S. and global) and LinkedIn (for U.S. and EMEA).
Merck-Eisai's Keytruda/Lenvima combo gets approval in Japan for kidney cancer
Feb. 25, 2022 7:13 AM ET
Merck & Co., Inc. (MRK), ESALY, ESALF
By: Ravikash, SA News Editor
- Merck (NYSE:MRK) and Eisai's (OTCPK:ESALF) (OTCPK:ESALY) drug combination of Keytruda and Lenvima was approved in Japan for radically unresectable or metastatic renal cell carcinoma (RCC), a type of kidney cancer.
- https://seekingalpha.com/news/3805827-merck-eisais-keytrudalenvima-combo-gets-approval-in-japan-for-kidney-cancer
- https://seekingalpha.com/symbol/ESALY
- https://seekingalpha.com/symbol/MRK
- https://www.keytrudalenvima.com/advanced-endometrial-cancer/
Jardiance (empagliflozin)
KEYTRUDA® (pembrolizumab) Plus LENVIMA® (lenvatinib)
KEYTRUDA® (pembrolizumab) Plus LENVIMA® (lenvatinib)
FDA Approves Treatment for Wider Range of Patients with Heart Failure
For Immediate Release:February 24, 2022
Today, the U.S. Food and Drug Administration approved Jardiance (empagliflozin) to reduce the risk of cardiovascular death and hospitalization for heart failure in adults.
Jardiance was originally approved by the FDA in 2014 as a supplement to diet and exercise to improve glucose control in adults with type 2 diabetes. Jardiance is also approved to reduce the risk of cardiovascular death in adults with type 2 diabetes and established cardiovascular disease, and to reduce the risk of death and hospitalization in patients with heart failure and low ejection fraction
“Today’s approval will provide a treatment option for a wider range of patients with heart failure,” said Norman Stockbridge, M.D., Ph.D., Director of the Division of Cardiology and Nephrology in the FDA’s Center for Drug Evaluation and Research. “While Jardiance may not be effective in all patients with heart failure, this approval is a significant step forward for patients and our understanding of heart failure. Coinciding with February’s annual observance of American Heart Month—a reminder for individuals to focus on cardiovascular health—this action will provide physicians another tool to address heart disease.”
Heart failure is a syndrome in which the heart is not meeting the needs of the body, affecting more than 650,000 people in the U.S. each year. Despite therapies in multiple drug classes, mortality remains high and treatment options for a broader range of patients are needed. Symptoms of heart failure vary but can include shortness of breath, fatigue and swelling in the legs. Heart failure becomes more common with age and is the leading cause of hospitalization in people over 65 years old.
For today’s approval, Jardiance’s safety and effectiveness were evaluated as an adjunct to standard of care therapy in a randomized, double-blind, international trial comparing 2,997 participants who received Jardiance, 10 mg, once daily to 2,991 participants who received the placebo. The main efficacy measurement was the time to death from cardiovascular causes or need to be hospitalized for heart failure. Of the individuals who received Jardiance for an average of about two years, 14% died from cardiovascular causes or were hospitalized for heart failure, compared to 17% of the participants who received the placebo. This benefit was mostly attributable to fewer patients being hospitalized for heart failure.
Jardiance received Priority Review designation for this indication.
The FDA granted the approval of Jardiance to Boehringer Ingelheim.
Related Information
Lilly-Boehringer Ingelheim's Jardiance granted expanded indication in heart failure
Feb. 24, 2022 3:24 PM ET
By: Jonathan Block, SA News Editor
- The U.S. FDA has granted an additional indiction to Eli Lilly (LLY +1.7%) and Boehringer Ingelheim's Jardiance (empagliflozin) to reduce the risk of cardiac death and hospitalization for heart failure patients.
- https://seekingalpha.com/news/3805360-lilly-boehringer-ingelheims-jardiance-granted-expanded-indication-in-heart-failure
- https://seekingalpha.com/symbol/LLY
- https://www.lilly.com/
- https://www.jardiance.com/
BIOTECNOVA™
Enhertu (trastuzumab deruxtecan)
Opdivo® (nivolumab) in Combination with CABOMETYX® (cabozantinib)
Opdivo® (nivolumab) in Combination with CABOMETYX® (cabozantinib)
21 February 2022 07:00 GMT
First HER2-low metastatic breast cancer Phase III results for AstraZeneca and Daiichi Sankyo’s Enhertu offer potential to redefine how the disease is classified and treated
Positive high-level results from the pivotal DESTINY-Breast04 Phase III trial showed Enhertu (trastuzumab deruxtecan) demonstrated a statistically significant and clinically meaningful improvement in both progression-free survival (PFS) and overall survival (OS) in patients with HER2-low unresectable and/or metastatic breast cancer regardless of hormone receptor (HR) status versus physician’s choice of chemotherapy.Enhertu is a HER2-directed antibody drug conjugate (ADC) being jointly developed by AstraZeneca and Daiichi Sankyo.All patients in the trial received a HER2 test, and the results were centrally confirmed. HER2-low status was defined as an immunohistochemistry (IHC) score of 1+ or IHC 2+ with a negative in-situ hybridisation (ISH) score.Up to 55% of all patients with breast cancer have tumours with a HER2 IHC score of 1+, or 2+ in combination with a negative ISH test, a level of HER2 expression not currently eligible for HER2-targeted therapy.1,2 HER2-low expression occurs in both HR-positive and HR-negative disease.3HER2 testing is well established to determine an appropriate treatment strategy in metastatic breast cancer. Targeting the lower range of HER2 expression may offer another approach to delay disease progression and extend survival in patients with metastatic breast cancer.4 Currently, chemotherapy remains the only treatment option both for patients with HR-positive tumours following progression on endocrine (hormone) therapy, and for those who are HR-negative.5DESTINY-Breast04 met its primary endpoint, where Enhertu demonstrated superior PFS in previously treated patients with HR-positive HER2-low metastatic breast cancer compared to the standard-of-care chemotherapy. The trial met the key secondary endpoint of PFS in patients with HER2-low metastatic breast cancer regardless of HR status (HR-positive or HR-negative). The trial also met the key secondary endpoints of OS in patients with HR-positive disease and in patients regardless of HR status at interim analysis.The safety profile of Enhertu was consistent with previous clinical trials, with no new safety concerns identified. Overall interstitial lung disease (ILD) rates were consistent with that observed in late-line HER2-positive breast cancer trials of Enhertu, with a lower rate of Grade 5 ILD observed as determined by an independent adjudication committee.Susan Galbraith, Executive Vice President, Oncology R&D, AstraZeneca said: “Today’s historic news from DESTINY-Breast04 could reshape how breast cancer is classified and treated. A HER2-directed therapy has never-before shown a benefit in patients with HER2-low metastatic breast cancer. These results for Enhertu are a huge step forward and could potentially expand our ability to target the full spectrum of HER2 expression, validating the need to change the way we categorise and treat breast cancer.”Ken Takeshita, Global Head, R&D, Daiichi Sankyo said: “Enhertu continues to redefine the treatment of HER2-targetable cancers. DESTINY-Breast04 is the first ever Phase III trial of a HER2-directed therapy in patients with HER2-low metastatic breast cancer to show statistically significant and clinically meaningful benefit in progression-free and overall survival compared to standard treatment. We look forward to sharing the detailed findings of DESTINY-Breast04 with the medical community and initiating discussions with regulatory agencies globally with the goal of bringing Enhertu to patients with metastatic breast cancer previously considered to be HER2-negative.”The data will be presented at a forthcoming medical meeting and shared with global health authorities.Enhertu (5.4mg/kg) is approved in more than 40 countries for the treatment of adult patients with unresectable or metastatic HER2-positive breast cancer who have received two or more prior anti-HER2-based regimens based on the results from the DESTINY-Breast01 trial.Enhertu is being further assessed in a comprehensive clinical development programme evaluating efficacy and safety across multiple HER2-targetable cancers, including breast, gastric, lung and colorectal cancers. DESTINY-Breast04
DESTINY-Breast04 is a global, randomised, open-label, registrational Phase III trial evaluating the efficacy and safety of Enhertu (5.4 mg/kg) versus physician’s choice of chemotherapy (capecitabine, eribulin, gemcitabine, paclitaxel or nab-paclitaxel) in patients with HR-positive (n=480) or HR-negative (n=60) HER2-low unresectable and/or metastatic breast cancer previously treated with one or two prior lines of chemotherapy. Patients were randomised 2:1 to receive either Enhertu or chemotherapy.The primary endpoint of DESTINY-Breast04 is PFS in patients with HR-positive disease based on blinded independent central review (BICR). Key secondary endpoints include PFS based on BICR in all randomised patients (regardless of HR status), OS in patients with HR-positive disease and OS in all randomised patients (regardless of HR status). Other secondary endpoints include PFS based on BICR and investigator assessment, duration of response based on BICR and safety.DESTINY-Breast04 enrolled approximately 540 patients at multiple sites in Asia, Europe and North America. For more information about the trial, visit ClinicalTrials.gov.
Enhertu
Enhertu is a HER2-directed ADC. Designed using Daiichi Sankyo’s proprietary DXd ADC technology, Enhertu is the lead ADC in the oncology portfolio of Daiichi Sankyo and the most advanced programme in AstraZeneca’s ADC scientific platform. Enhertu consists of a HER2 monoclonal antibody attached to a topoisomerase I inhibitor payload, an exatecan derivative, via a stable tetrapeptide-based cleavable linker.Enhertu (5.4mg/kg) is approved in more than 40 countries for the treatment of adult patients with unresectable or metastatic HER2-positive breast cancer who have received two or more prior anti-HER2-based regimens based on the results from the DESTINY-Breast01 trial.Enhertu (6.4mg/kg) is approved in several countries for the treatment of adult patients with locally advanced or metastatic HER2-positive gastric or gastroesophageal junction (GEJ) adenocarcinoma who have received a prior trastuzumab-based regimen based on the results from the DESTINY-Gastric01 trial.https://www.enhertu.com/en/
Daiichi Sankyo collaboration
Daiichi Sankyo Company, Limited (referred to as Daiichi Sankyo) and AstraZeneca entered into a global collaboration to jointly develop and commercialise Enhertu (a HER2-directed ADC) in March 2019, and datopotamab deruxtecan (DS-1062; a TROP2-directed ADC) in July 2020, except in Japan where Daiichi Sankyo maintains exclusive rights. Daiichi Sankyo is responsible for manufacturing and supply of Enhertu and datopotamab deruxtecan.
Please visit astrazeneca.com and follow the Company on Twitter @AstraZeneca.
AstraZeneca gains on positive late-stage data for breast cancer therapy
Feb. 21, 2022 9:52 AM ET
AstraZeneca PLC (AZN), DSKYF, DSNKY
By: Dulan Lokuwithana, SA News Editor1 Comment AstraZeneca (NASDAQ:AZN) shares outperformed the broader market in London on Monday in reaction to positive late-stage data for Enhertu in a group of breast cancer patients with low levels of a protein called HER2.The Anglo-Swedish drugmaker has partnered with Daiichi Sankyo (OTCPK:DSKYF) (OTCPK:DSNKY) to design Enhertu as an antibody-drug conjugate (ADC) targeted at HER2, a tyrosine kinase receptor expressed on multiple types of cancer.https://seekingalpha.com/news/3802228-azn-stock-gains-on-positive-data-for-breast-cancer-therapyhttps://seekingalpha.com/symbol/AZNhttps://seekingalpha.com/symbol/DSKYFhttps://seekingalpha.com/symbol/DSNKYhttps://www.enhertu.com/en/https://www.astrazeneca.com/
Opdivo® (nivolumab) in Combination with CABOMETYX® (cabozantinib)
Opdivo® (nivolumab) in Combination with CABOMETYX® (cabozantinib)
Opdivo® (nivolumab) in Combination with CABOMETYX® (cabozantinib)
Opdivo® (nivolumab) in Combination with CABOMETYX® (cabozantinib) Demonstrates Continued Survival Benefits with Over Two Years of Follow-Up in the CheckMate -9ER Trial in First-Line Advanced Renal Cell Carcinoma
Opdivo® (nivolumab) in Combination with CABOMETYX® (cabozantinib) Demonstrates Continued Survival Benefits with Over Two Years of Follow-Up in the CheckMate -9ER Trial in First-Line Advanced Renal Cell CarcinomaPDF Version- Updated results to be presented at ASCO GU 2022 show sustained efficacy benefits with Opdivo in combination with CABOMETYX compared to sunitinib- Patients treated with Opdivo and CABOMETYX continue to report improvements in health-related quality of life in a separate analysisPRINCETON, N.J. & ALAMEDA, Calif.--(BUSINESS WIRE)--Today Bristol Myers Squibb (NYSE: BMY) and Exelixis, Inc. (NASDAQ: EXEL) announced two-year (25.4 months minimum; 32.9 months median) follow-up results from analyses of the Phase 3 CheckMate -9ER trial, demonstrating sustained survival and response rate benefits, as well as health-related quality of life (HRQoL) improvements, with the combination of Opdivo® (nivolumab) and CABOMETYX® (cabozantinib) versus sunitinib in the first-line treatment of advanced renal cell carcinoma (RCC). These updated results will be featured in two poster presentations at the American Society of Clinical Oncology (ASCO) 2022 Genitourinary Cancers Symposium from February 17-19, 2022.“The new data from CheckMate -9ER evaluating nivolumab and cabozantinib are significant for patients with first-line advanced renal cell carcinoma, as they provide further evidence of efficacy benefits as well as favorable patient-reported quality of life outcomes with this combination,” said Toni Choueiri, M.D., Director of the Lank Center for Genitourinary Oncology at Dana-Farber Cancer Institute and Jerome and Nancy Kohlberg Professor of Medicine at Harvard Medical School. “As clinicians, we are constantly looking for therapies that can help more patients control their disease without reporting a detriment in their quality of life.”
Abstract #350: Final overall survival analysis and organ-specific target lesion assessments with 2-year follow-up in CheckMate 9ER: nivolumab plus cabozantinib vs sunitinib for patients with advanced renal cell carcinoma (Powles, et. al.)With median follow-up of 32.9 months (25.4 months minimum), Opdivo in combination with CABOMETYX (n=323) continued to show superior overall survival (OS), progression-free survival (PFS), objective response rates (ORR), duration of response (DoR) and complete response (CR) rates compared to sunitinib (n=328). No new safety signals emerged with extended follow-up. In the full study population:
- OS: At the final OS analysis, Opdivo in combination with CABOMETYX continued to show meaningful improvements in median OS (37.7 months vs. 34.3 months) and demonstrated a 30% reduction in the risk of death (Hazard Ratio [HR] 0.70; 95% Confidence Interval [CI]: 0.55 to 0.90) compared to sunitinib.
- PFS: PFS benefits were maintained, with the combination continuing to double median PFS vs. sunitinib (16.6 months vs. 8.3 months, respectively; HR 0.56; 95% CI: 0.46 to 0.68).
- ORR and DoR: ORR benefits were sustained, with nearly twice as many patients responding to Opdivo in combination with CABOMETYX vs. sunitinib (55.7% vs. 28.4%). Responses were also more durable with the combination, with a median DoR of 23.1 months, compared to 15.1 months with sunitinib.
- CR: CR rates more than doubled among patients treated with the combination, with 12.4% having a CR vs. 5.2% of those treated with sunitinib.
- Safety: 97.2% of patients treated with Opdivo plus CABOMETYX (n=320) experienced a treatment-related adverse event (TRAE) of any grade, compared to 93.1% of patients treated with sunitinib (n=320); 65.0% vs. 54.1% had a grade ≥3 TRAE, respectively.
Additionally, in an exploratory analysis of depth of response in target lesions by organ site, a higher percentage of patients experienced any tumor shrinkage benefits with Opdivo in combination with CABOMETYX vs. sunitinib across lung (90.5% vs. 76.0%), lymph node (88.4% vs. 72.6%), kidney (89.0% vs. 71.6%), liver (72.7% vs. 53.8%) and bone (85.2% vs. 65.0%) target lesions.
Abstract #323: Health-related quality of life (HRQoL) in previously untreated patients with advanced renal cell carcinoma (aRCC): CheckMate 9ER updated results. (Cella, et. al.)In a separate analysis with 32.9 months median follow-up from the CheckMate -9ER trial, patients continued to report clinically meaningful HRQoL benefits with Opdivo in combination with CABOMETYX compared to sunitinib. HRQoL scores were improved or maintained over time amongst patients treated with the combination, while reductions in scores were observed with sunitinib. Additionally, those who received Opdivo in combination with CABOMETYX were 48% less likely to be notably bothered by treatment side effects than patients in the sunitinib arm. These exploratory outcomes were measured using Functional Assessment of Cancer Therapy Kidney Symptom Index-19 (FKSI-19), a quality of life tool specific to kidney cancer, and EQ-5D-3L instruments.“The results from these analyses of CheckMate -9ER provide additional clinical evidence supporting Opdivo in combination with CABOMETYX as an important first-line treatment for patients with advanced renal cell carcinoma who may benefit from an immunotherapy plus tyrosine kinase inhibitor regimen,” said Dana Walker, M.D., M.S.C.E., vice president, development program lead, genitourinary cancers, Bristol Myers Squibb. “These results exemplify the collaborative nature of our approach to research and development and demonstrate how we’re working across the healthcare landscape to explore how our therapies may work with potentially complementary mechanisms of action to help more patients achieve better and longer-lasting outcomes.”“We are pleased that these additional findings from CheckMate -9ER showing continued superior efficacy and improved quality of life with longer follow-up are being presented at ASCO GU, as they further indicate the value of CABOMETYX in combination with Opdivo as a first-line option for patients with advanced renal cell carcinoma,” said Vicki L. Goodman, M.D., Executive Vice President, Product Development and Medical Affairs, and Chief Medical Officer, Exelixis. “The positive data from CheckMate -9ER, which are a culmination of a robust collaborative effort with Bristol Myers Squibb, reinforce our commitment to advancing additional CABOMETYX-based regimens in our continuing journey to identify treatments for people with difficult-to-treat cancers.”Bristol Myers Squibb and Exelixis thank the patients and investigators involved in the CheckMate -9ER clinical trial.
About CheckMate -9ER
CheckMate -9ER is an open-label, randomized, multi-national Phase 3 trial evaluating patients with previously untreated advanced or metastatic renal cell carcinoma (RCC). A total of 651 patients (23% favorable risk, 58% intermediate risk, 20% poor risk; 25% PD-L1≥1%) were randomized to receive Opdivo plus CABOMETYX (n=323) vs. sunitinib (n=328). The primary endpoint is progression-free survival (PFS). Secondary endpoints include overall survival (OS) and objective response rate (ORR). The primary efficacy analysis is comparing the doublet combination vs. sunitinib in all randomized patients. The trial is sponsored by Bristol Myers Squibb and Ono Pharmaceutical Co and co-funded by Exelixis, Inc., Ipsen and Takeda Pharmaceutical Company Limited.
About OPDIVO
®Opdivo is a programmed death-1 (PD-1) immune checkpoint inhibitor that is designed to uniquely harness the body’s own immune system to help restore anti-tumor immune response. By harnessing the body’s own immune system to fight cancer, Opdivo has become an important treatment option across multiple cancers.Opdivo’s leading global development program is based on Bristol Myers Squibb’s scientific expertise in the field of Immuno-Oncology and includes a broad range of clinical trials across all phases, including Phase 3, in a variety of tumor types. To date, the Opdivo clinical development program has treated more than 35,000 patients. The Opdivo trials have contributed to gaining a deeper understanding of the potential role of biomarkers in patient care, particularly regarding how patients may benefit from Opdivo across the continuum of PD-L1 expression.In July 2014, Opdivo was the first PD-1 immune checkpoint inhibitor to receive regulatory approval anywhere in the world. Opdivo is currently approved in more than 65 countries, including the United States, the European Union, Japan and China. In October 2015, the Company’s Opdivo and Yervoy combination regimen was the first Immuno-Oncology combination to receive regulatory approval for the treatment of metastatic melanoma and is currently approved in more than 50 countries, including the United States and the European Union.https://www.opdivo.com/
OPDIVO INDICATIONS
OPDIVO® (nivolumab), as a single agent, is indicated for the treatment of patients with unresectable or metastatic melanoma.OPDIVO® (nivolumab), in combination with YERVOY® (ipilimumab), is indicated for the treatment of patients with unresectable or metastatic melanoma.OPDIVO® (nivolumab) is indicated for the adjuvant treatment of patients with melanoma with involvement of lymph nodes or metastatic disease who have undergone complete resection.OPDIVO® (nivolumab), in combination with YERVOY® (ipilimumab), is indicated for the first-line treatment of adult patients with metastatic non-small cell lung cancer (NSCLC) whose tumors express PD-L1 (≥1%) as determined by an FDA-approved test, with no EGFR or ALK genomic tumor aberrations.OPDIVO® (nivolumab), in combination with YERVOY® (ipilimumab) and 2 cycles of platinum-doublet chemotherapy, is indicated for the first-line treatment of adult patients with metastatic or recurrent non-small cell lung cancer (NSCLC), with no EGFR or ALK genomic tumor aberrations.OPDIVO® (nivolumab) is indicated for the treatment of patients with metastatic non-small cell lung cancer (NSCLC) with progression on or after platinum-based chemotherapy. Patients with EGFR or ALK genomic tumor aberrations should have disease progression on FDA-approved therapy for these aberrations prior to receiving OPDIVO.OPDIVO® (nivolumab), in combination with YERVOY® (ipilimumab), is indicated for the first-line treatment of adult patients with unresectable malignant pleural mesothelioma (MPM).OPDIVO® (nivolumab), in combination with YERVOY® (ipilimumab), is indicated for the first-line treatment of patients with intermediate or poor risk advanced renal cell carcinoma (RCC).OPDIVO® (nivolumab), in combination with cabozantinib, is indicated for the first-line treatment of patients with advanced renal cell carcinoma (RCC).OPDIVO® (nivolumab) is indicated for the treatment of patients with advanced renal cell carcinoma (RCC) who have received prior anti-angiogenic therapy.OPDIVO® (nivolumab) is indicated for the treatment of adult patients with classical Hodgkin lymphoma (cHL) that has relapsed or progressed after autologous hematopoietic stem cell transplantation (HSCT) and brentuximab vedotin or after 3 or more lines of systemic therapy that includes autologous HSCT. This indication is approved under accelerated approval based on overall response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.OPDIVO® (nivolumab) is indicated for the treatment of patients with recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN) with disease progression on or after platinum-based therapy.OPDIVO® (nivolumab) is indicated for the treatment of patients with locally advanced or metastatic urothelial carcinoma who have disease progression during or following platinum-containing chemotherapy or have disease progression within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy.OPDIVO® (nivolumab), as a single agent, is indicated for the adjuvant treatment of patients with urothelial carcinoma (UC) who are at high risk of recurrence after undergoing radical resection of UC.OPDIVO® (nivolumab), as a single agent, is indicated for the treatment of adult and pediatric (12 years and older) patients with microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) metastatic colorectal cancer (CRC) that has progressed following treatment with a fluoropyrimidine, oxaliplatin, and irinotecan. This indication is approved under accelerated approval based on overall response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.OPDIVO® (nivolumab), in combination with YERVOY® (ipilimumab), is indicated for the treatment of adults and pediatric patients 12 years and older with microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) metastatic colorectal cancer (CRC) that has progressed following treatment with a fluoropyrimidine, oxaliplatin, and irinotecan. This indication is approved under accelerated approval based on overall response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.OPDIVO® (nivolumab), in combination with YERVOY® (ipilimumab), is indicated for the treatment of patients with hepatocellular carcinoma (HCC) who have been previously treated with sorafenib. This indication is approved under accelerated approval based on overall response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.OPDIVO® (nivolumab) is indicated for the treatment of patients with unresectable advanced, recurrent or metastatic esophageal squamous cell carcinoma (ESCC) after prior fluoropyrimidine- and platinum-based chemotherapy.OPDIVO® (nivolumab) is indicated for the adjuvant treatment of completely resected esophageal or gastroesophageal junction cancer with residual pathologic disease in patients who have received neoadjuvant chemoradiotherapy (CRT).OPDIVO® (nivolumab), in combination with fluoropyrimidine- and platinum- containing chemotherapy, is indicated for the treatment of patients with advanced or metastatic gastric cancer, gastroesophageal junction cancer, and esophageal adenocarcinoma.
About CABOMETYX® (cabozantinib)
In the U.S., CABOMETYX tablets are approved for the treatment of patients with advanced RCC; for the treatment of patients with hepatocellular carcinoma who have been previously treated with sorafenib; for patients with advanced RCC as a first-line treatment in combination with nivolumab; and for adult and pediatric patients 12 years of age and older with locally advanced or metastatic differentiated thyroid cancer that has progressed following prior VEGFR-targeted therapy and who are radioactive iodine-refractory or ineligible. CABOMETYX tablets have also received regulatory approvals in the European Union and additional countries and regions worldwide. In 2016, Exelixis granted Ipsen exclusive rights for the commercialization and further clinical development of cabozantinib outside of the U.S. and Japan. In 2017, Exelixis granted exclusive rights to Takeda Pharmaceutical Company Limited for the commercialization and further clinical development of cabozantinib for all future indications in Japan. Exelixis holds the exclusive rights to develop and commercialize cabozantinib in the U.S.https://www.cabometyx.com/https://www.cabometyx.com/kidney-cancer/cabometyx-opdivo
For more information about Bristol Myers Squibb, visit us at BMS.com or follow us on LinkedIn, Twitter, YouTube, Facebook and Instagram.
For more information about Exelixis, please visit www.exelixis.com, follow @ExelixisInc on Twitter or like Exelixis, Inc. on Facebook. Exelixis, the Exelixis logo, CABOMETYX and COMETRIQ are registered U.S. trademarks of Exelixis.COTELLIC is a registered trademark of Genentech, Inc.MINNEBRO is a registered trademark of Daiichi Sankyo Company, Limited.
Exelixis/Bristol-Myers' drug combo shows sustained survival benefits in kidney cancer
Feb. 15, 2022 6:36 AM ET
Ipsen S.A. (IPSEY), IPSEFEXEL, BMY, TAK
By: Ravikash, SA News Editor3 Comments Ipsen (OTCPK:IPSEF) said two-year follow-up data from a phase 3 CheckMate -9ER trial, showed sustained survival benefits, and health related quality of life (HRQoL) improvements with the combination of Exelixis (NASDAQ:EXEL) Cabometyx (cabozantinib) and Bristol-Myers Squibb's (NYSE:BMY) Opdivo (nivolumab) against sunitinib as first-line treatment of advanced renal cell carcinoma (aRCC).https://seekingalpha.com/news/3799945-exelixisbristol-myers-drug-combo-shows-sustained-survival-benefits-in-kidney-cancerhttps://seekingalpha.com/symbol/EXELhttps://seekingalpha.com/symbol/BMYhttps://www.opdivo.com/https://www.cabometyx.com/https://www.cabometyx.com/kidney-cancer/cabometyx-opdivo
Veklury® (Remdesivir)
Opdivo® (nivolumab) in Combination with CABOMETYX® (cabozantinib)
VENCLEXTA® (venetoclax) in Combination with Azacitidine
February 11, 2022
Veklury® (Remdesivir) Retains Antiviral Activity Against Omicron, Delta and Other Emergent SARS-CoV-2 Variants in Multiple In Vitro Studies
-- Data Supports the Continued Use of Veklury for Treatment of COVID-19 for Current SARS-CoV-2 Variants --FOSTER CITY, Calif.--(BUSINESS WIRE)-- Gilead Sciences, Inc. (Nasdaq: GILD) today released data demonstrating the in vitro activity of Veklury® (remdesivir) against ten SARS-CoV-2 variants, including Omicron. Results of Gilead studies are consistent with other in vitro studies independently conducted by researchers from institutions in other countries, including Belgium, Czech Republic, Germany, Poland, and the United States, which confirmed Veklury’s antiviral activity against multiple previously identified variants of SARS-CoV-2, including Alpha, Beta, Gamma, Delta and Omicron.The study analyzed in vitro antiviral activity by two methods to understand the susceptibility of ten major SARS-CoV-2 variants to Veklury. The study results showed similar activity of Veklury against the variants and an early ancestral A lineage isolate detected in Seattle, WA (WA1 strain). Specifically, Delta and Omicron variants both remained fully susceptible to Veklury, and these laboratory results demonstrate that Veklury has remained active against all major variants isolated over the past two years.Veklury directly inhibits viral replication inside host cells by targeting the SARS-CoV-2 RNA-dependent RNA polymerase. On entering the body, Veklury is transformed into the active triphosphate metabolite, which is then incorporated into the viral RNA and stops replication of the virus within the infected cells. The study analyzed nearly 6 million publicly available variant isolate sequences and confirmed that the nsp12 protein, the RNA polymerase target of Veklury, is highly conserved across all variants. Further characterization confirmed that none of the few identified nsp12 mutations prevalent in some of the SARS-CoV-2 variants affects the virus susceptibility to Veklury.“These results provide evidence of the consistent and durable antiviral activity of remdesivir across known variants that have emerged throughout the pandemic, including Omicron and support its continued use for the treatment of COVID-19 for current SARS-CoV-2 variants,” said Tomas Cihlar, Senior Vice President of Virology Research, Gilead Sciences. “Now with a new version of Omicron (BA.2 subvariant) increasing in circulation around the world, these latest data also suggest that remdesivir will retain antiviral activity against this new subvariant because the viral RNA polymerase that remdesivir targets does not contain any additional unique mutations. Gilead continuously evaluates the activity of Veklury against viral variants.”The results of this study have been submitted for publication in a peer-reviewed journal and have been uploaded as preprint at BioRxiv available here.
About Veklury
Veklury (remdesivir) is a nucleotide analog invented by Gilead, building on more than a decade of the company’s antiviral research. Veklury is the antiviral standard of care for the treatment of hospitalized patients with COVID-19 and is a recommended treatment for reducing disease progression in non-hospitalized patients at high risk of disease progression. At this time, more than half of patients hospitalized with COVID-19 in the United States are treated with Veklury. It can help reduce disease progression across a spectrum of disease severity and enable patients to recover faster, freeing up limited hospital resources and saving healthcare systems money.Veklury was approved by the U.S. Food and Drug Administration (FDA) on October 22, 2020 for adults and pediatric patients 12 years of age and older and weighing at least 40 kg for the treatment of COVID-19 requiring hospitalization. On January 21, 2022, the FDA approved a supplemental new drug application (sNDA) for Veklury to expand the indication to the treatment of non-hospitalized adult and adolescent patients who are at high risk of progression to severe COVID-19, including hospitalization or death. The expanded indication allows for Veklury to be administered in qualified outpatient settings that can administer daily intravenous (IV) infusions over three consecutive days. Veklury is contraindicated in patients who are allergic to Veklury or any of its components; please see below for additional Important Safety Information for Veklury.Veklury is approved or authorized for temporary use in approximately 50 countries worldwide. To date, Veklury and generic remdesivir have been made available to more than 10 million patients around the world, including nearly 7 million people in 127 middle- and low-income countries through Gilead’s voluntary licensing program. These licenses currently remain royalty-free, reflecting Gilead’s existing commitment to enabling broad patient access to remdesivir.
U.S. Indication for Veklury
Veklury® (remdesivir 100 mg for injection) is indicated for the treatment of COVID-19 in adults and pediatric patients (12 years of age and older and weighing at least 40 kg) with positive results of direct SARS-CoV-2 viral testing, who are:
- Hospitalized, or
- Not hospitalized and have mild-to-moderate COVID-19 and are at high risk for progression to severe COVID-19, including hospitalization or death.
Veklury should only be administered in settings in which health care providers have immediate access to medications to treat a severe infusion or hypersensitivity reaction, such as anaphylaxis, and the ability to activate the emergency medical system (EMS), as necessary. Veklury must be administered by intravenous infusion. Veklury is contraindicated in patients who are allergic to Veklury or any of its components. For more information, please see the U.S. full Prescribing Information available at www.gilead.com
.https://www.vekluryhcp.com/
U.S. full Prescribing Information for Veklury is available at www.gilead.com. Veklury, Gilead and the Gilead logo are registered trademarks of Gilead Sciences, Inc., or its related companies.For more information about Gilead, please visit the company’s website at www.gilead.com , follow Gilead on Twitter (@Gilead Sciences) or call Gilead Public Affairs at 1-800-GILEAD-5 or 1-650-574-3000.View source version on businesswire.com: https://www.businesswire.com/news/home/20220211005143/en/ Source: Gilead Sciences, Inc.
Gilead's remdesivir effective against multiple COVID variants, including Omicron
Feb. 11, 2022 8:46 AM ET
By: Jonathan Block, SA News Editor
📷Bill Oxford/iStock via Getty Images New data released by Gilead Sciences (NASDAQ:GILD) indicates that its COVID-19 treatment Veklury (remdesivir) is effective against 10 variants, including Omicron.
VENCLEXTA® (venetoclax) in Combination with Azacitidine
ADCETRIS (brentuximab vedotin) in combination with chemotherapy
VENCLEXTA® (venetoclax) in Combination with Azacitidine
AbbVie Announces First Provincial Reimbursements for VENCLEXTA® (venetoclax) in Combination with Azacitidine for Acute Myeloid Leukemia (AML) Patients
Feb. 10, 2022 7:00 AM ET
- Following the signing of an agreement between AbbVie and the pan-Canadian Pharmaceutical Alliance (pCPA), Quebec, Saskatchewan, and Manitoba are the first provinces to reimburse the combination treatment for newly diagnosed acute myeloid leukemia (AML) patients who are ineligible for intensive induction chemotherapy.
MONTREAL, Feb. 10, 2022 /CNW/ - AbbVie (ABBV), a research-based global biopharmaceutical company, announced today that an agreement was reached with the pan-Canadian Pharmaceutical Alliance (pCPA) for VENCLEXTA® (venetoclax) in combination with azacitidine for the treatment of patients with newly diagnosed acute myeloid leukemia (AML) who are 75 years or older, or who have comorbidities that preclude use of intensive induction chemotherapy.i
Effective February 2nd, on Québec's Liste des medicaments-établissements, effective February 1st on Saskatchewan Cancer Agency drug formulary, and effective February 24th on Manitoba's Drug Benefits and Interchangeability Formulary, VENCLEXTA is listed in combination with azacitidine, for first line treatment of patients with newly diagnosed AML who are 75 years or older, or who have comorbidities that preclude use of intensive induction chemotherapy. For full criteria, consult the list of medications in effect.ii, iii, iv
"Acute myeloid leukemia is a blood cancer with a survival rate that still needs to be improved. Intensive chemotherapy treatments lead to toxicity, which can limit their use. However, our understanding of this disease has improved considerably over the past few years and, thanks to new treatment options such as the combination of venetoclax and azacitidine, we are now able to effectively treat a greater proportion of patients," explains Dr. Julie Bergeron, MD, FRCPC, associate clinical professor, head of the Optilab CHUM cluster of hematology laboratories, and hematologist at the CEMTL Maisonneuve-Rosemont facility.
In Canada, the five-year net survival rate is approximately 21% for people diagnosed with AML in the general population. v
"Every day, we aim to transform the standard of care in Oncology. Having effective and proven treatment options is vital for patients and their families impacted by AML. It is great news that VENCLEXTA plus azacitidine is now reimbursed in Quebec, Saskatchewan and Manitoba for people living with AML," says Tracey Ramsay, Vice President and General Manager, AbbVie Canada.
VENCLEXTA in combination with azacitidine was approved by Health Canada in December 2020. Health Canada's approval was granted under Project Orbis, an FDA initiative which provides a framework for concurrent submission and accelerated review of oncology products among international partners.
VENCLEXTA is jointly commercialized by AbbVie and Genentech, a member of the Roche Group, in the U.S. and by AbbVie outside of the U.S.
For more information about AbbVie, please visit us at www.abbvie.ca. Follow @abbviecanada on Twitter or find us on LinkedIn.
SOURCE AbbVie Canada
https://seekingalpha.com/symbol/ABBV
https://chemocare.com/chemotherapy/drug-info/Vidaza.aspx
KEYTRUDA® (pembrolizumab)
ADCETRIS (brentuximab vedotin) in combination with chemotherapy
ADCETRIS (brentuximab vedotin) in combination with chemotherapy
Pivotal Phase 3 Data for KEYTRUDA® (pembrolizumab) in High-Risk Early-Stage Triple-Negative Breast Cancer (TNBC) Published in the New England Journal of Medicine
February 9, 2022 5:00 pm ETKENILWORTH, N.J.--(BUSINESS WIRE)-- Merck (NYSE: MRK), known as MSD outside the United States and Canada, today announced the publication of results from the Phase 3 KEYNOTE-522 trial in the Feb. 10, 2022 edition of the New England Journal of Medicine. Results showed that neoadjuvant KEYTRUDA, Merck’s anti-PD-1 therapy, in combination with chemotherapy followed by adjuvant KEYTRUDA as monotherapy (the KEYTRUDA regimen), significantly prolonged event-free survival (EFS) compared with neoadjuvant chemotherapy followed by adjuvant placebo (the chemotherapy-placebo regimen) in patients with high-risk early-stage triple-negative breast cancer (TNBC).As previously reported, after a median follow-up of 39 months, the KEYTRUDA regimen reduced the risk of events or death by 37% (HR=0.63 [95% CI, 0.48-0.82]; p<0.001) versus the chemotherapy-placebo regimen. A total of 15.7% (n= 123/784) of patients who received the KEYTRUDA regimen had an EFS event compared to 23.8% (n= 93/390) of patients who received the chemotherapy-placebo regimen. The estimated three-year EFS rates were 84.5% (95% CI, 81.7-86.9) in the KEYTRUDA group compared with 76.8% (95% CI, 72.2-80.7) in the chemotherapy-placebo group. Event-free survival was defined as the time from randomization to the first occurrence of either disease progression that precluded definitive surgery, a local/distant recurrence, a second primary malignancy, or death from any cause. The safety profile of the KEYTRUDA regimen was consistent with the known profiles of each regimen, and no new safety concerns were identified. Additional detailed efficacy and safety data are also featured in the publication.KEYTRUDA in combination with chemotherapy as neoadjuvant treatment and then continued as a single agent as adjuvant treatment after surgery is approved in the U.S. for the treatment of patients with high-risk early-stage TNBC. Additional global regulatory submissions are ongoing.“These data, which supported the FDA approval and updates to the NCCN guidelines, establish that KEYTRUDA plus chemotherapy as neoadjuvant therapy followed by adjuvant KEYTRUDA could change clinical practice for the treatment of patients with high-risk early-stage TNBC,” said Dr. Peter Schmid, lead, Centre for Experimental Cancer Medicine, Barts Cancer Institute in London, England. “KEYNOTE-522 is the first prospective randomized Phase 3 trial to show an improvement in event-free survival among patients with stage II and stage III TNBC.”“The study of KEYTRUDA in earlier disease states has long been a critical aspect of our clinical program,” Dr. Roy Baynes, senior vice president and head of global clinical development, chief medical officer, Merck Research Laboratories. “We are incredibly proud that the New England Journal of Medicine has chosen to publish data from this pivotal neoadjuvant/adjuvant trial of KEYTRUDA in high-risk early-stage TNBC for the second time. Results from KEYNOTE-522, in which the KEYTRUDA regimen showed a significant 37% reduction in the risk of EFS events compared to neoadjuvant chemotherapy, represent an important advance and support earlier intervention with KEYTRUDA in these patients.”Merck is rapidly advancing a broad portfolio in gynecologic and breast cancers with an extensive clinical development program for KEYTRUDA and several other investigational and approved medicines across these areas.
Study Design and Additional Data From KEYNOTE-522
KEYNOTE-522 is a Phase 3, randomized, double-blind trial (ClinicalTrials.gov, NCT03036488). The dual primary endpoints are pathological complete response (pCR), defined as pathological stage ypT0/Tis ypN0 at the time of definitive surgery, and EFS, defined as the time from randomization to the first occurrence of either disease progression that precluded definitive surgery, a local/distant recurrence, a second primary cancer, or death from any cause in all patients randomized. Secondary endpoints include pCR rate using alternative definitions, overall survival (OS) in all patients randomized, pCR rate according to all definitions, EFS and OS in patients whose tumors express PD-L1 (Combined Positive Score [CPS] ≥1), safety and health-related quality of life assessments. The study enrolled 1,174 patients who were randomized 2:1 to receive either:
- The KEYTRUDA regimen: KEYTRUDA (every three weeks) plus paclitaxel (weekly) and carboplatin (weekly or every three weeks) for four cycles, followed by KEYTRUDA plus cyclophosphamide and either doxorubicin or epirubicin (every three weeks) for four cycles as neoadjuvant therapy prior to surgery, followed by nine cycles of KEYTRUDA (every three weeks) as adjuvant therapy post-surgery (n=784); or
- The chemotherapy-placebo regimen: Placebo (every three weeks) plus paclitaxel (weekly) and carboplatin (weekly or every three weeks) for four cycles, followed by placebo plus cyclophosphamide and either doxorubicin or epirubicin (every three weeks) for four cycles as neoadjuvant therapy prior to surgery, followed by nine cycles of placebo (every three weeks) as adjuvant therapy post-surgery (n=390).
As previously announced, KEYNOTE-522 met the success criterion for the dual primary endpoint of pCR at the first interim analysis; pCR was observed in 64.8% of patients who received KEYTRUDA plus chemotherapy (n=260/401), an increase of 13.6% (p=0.00055) from 51.2% in patients who received placebo plus chemotherapy (n=103/201). At the fourth interim analysis, KEYNOTE-522 met the success criterion for the dual primary endpoint of EFS. The trial also evaluated OS, a key secondary endpoint. Although the OS data did not cross the boundary for statistical significance at the fourth interim analysis, there was a 28% reduction in the risk of death with the KEYTRUDA regimen versus the chemotherapy-placebo regimen (HR=0.72 [95% CI, 0.51-1.02]). The study is continuing to allow for additional follow-up of OS.For the combined neoadjuvant and adjuvant phases, treatment-related adverse events Grade 3 or higher occurred in 77.1% of patients receiving the KEYTRUDA regimen (n=783) and in 73.3% of patients receiving the chemotherapy-placebo regimen (n=389). Treatment-related adverse events led to death in 0.5% of patients receiving the KEYTRUDA regimen (n=4) and 0.3% of patients receiving the chemotherapy-placebo regimen (n=1). No new safety concerns were identified.Immune-mediated adverse events (AEs) of any grade occurred in 33.5% of patients receiving the KEYTRUDA regimen and 11.3% of patients receiving the chemotherapy-placebo regimen. A higher incidence of endocrine disorders was observed with the KEYTRUDA regimen as compared to the chemotherapy-placebo regimen. Immune-mediated AEs led to death in 0.3% of patients receiving the KEYTRUDA regimen (n=2) and no patients receiving the chemotherapy-placebo regimen. Most immune-mediated AEs occurred during the neoadjuvant phase rather than the adjuvant phase.
About KEYTRUDA® (pembrolizumab) Injection, 100 mg
KEYTRUDA is an anti-programmed death receptor-1 (PD-1) therapy that works by increasing the ability of the body’s immune system to help detect and fight tumor cells. KEYTRUDA is a humanized monoclonal antibody that blocks the interaction between PD-1 and its ligands, PD-L1 and PD-L2, thereby activating T lymphocytes which may affect both tumor cells and healthy cells.Merck has the industry’s largest immuno-oncology clinical research program. There are currently more than 1,700 trials studying KEYTRUDA across a wide variety of cancers and treatment settings. The KEYTRUDA clinical program seeks to understand the role of KEYTRUDA across cancers and the factors that may predict a patient's likelihood of benefitting from treatment with KEYTRUDA, including exploring several different biomarkers.
Selected KEYTRUDA® (pembrolizumab) Indications in the U.S.
MelanomaKEYTRUDA is indicated for the treatment of patients with unresectable or metastatic melanoma.KEYTRUDA is indicated for the adjuvant treatment of adult and pediatric (12 years and older) patients with stage IIB, IIC, or III melanoma following complete resection.Non-Small Cell Lung CancerKEYTRUDA, in combination with pemetrexed and platinum chemotherapy, is indicated for the first-line treatment of patients with metastatic nonsquamous non-small cell lung cancer (NSCLC), with no EGFR or ALK genomic tumor aberrations.KEYTRUDA, in combination with carboplatin and either paclitaxel or paclitaxel protein-bound, is indicated for the first-line treatment of patients with metastatic squamous NSCLC.KEYTRUDA, as a single agent, is indicated for the first-line treatment of patients with NSCLC expressing PD-L1 [tumor proportion score (TPS) ≥1%] as determined by an FDA-approved test, with no EGFR or ALK genomic tumor aberrations, and is:
- stage III where patients are not candidates for surgical resection or definitive chemoradiation, or
- metastatic.
KEYTRUDA, as a single agent, is indicated for the treatment of patients with metastatic NSCLC whose tumors express PD-L1 (TPS ≥1%) as determined by an FDA-approved test, with disease progression on or after platinum-containing chemotherapy. Patients with EGFR or ALK genomic tumor aberrations should have disease progression on FDA-approved therapy for these aberrations prior to receiving KEYTRUDA.Head and Neck Squamous Cell CancerKEYTRUDA, in combination with platinum and fluorouracil (FU), is indicated for the first-line treatment of patients with metastatic or with unresectable, recurrent head and neck squamous cell carcinoma (HNSCC).KEYTRUDA, as a single agent, is indicated for the first-line treatment of patients with metastatic or with unresectable, recurrent HNSCC whose tumors express PD-L1 [combined positive score (CPS) ≥1] as determined by an FDA-approved test.KEYTRUDA, as a single agent, is indicated for the treatment of patients with recurrent or metastatic HNSCC with disease progression on or after platinum-containing chemotherapy.Classical Hodgkin LymphomaKEYTRUDA is indicated for the treatment of adult patients with relapsed or refractory classical Hodgkin lymphoma (cHL).KEYTRUDA is indicated for the treatment of pediatric patients with refractory cHL, or cHL that has relapsed after 2 or more lines of therapy.Primary Mediastinal Large B-Cell LymphomaKEYTRUDA is indicated for the treatment of adult and pediatric patients with refractory primary mediastinal large B-cell lymphoma (PMBCL), or who have relapsed after 2 or more prior lines of therapy.KEYTRUDA is not recommended for treatment of patients with PMBCL who require urgent cytoreductive therapy.Urothelial CarcinomaKEYTRUDA is indicated for the treatment of patients with locally advanced or metastatic urothelial carcinoma (mUC):
- who are not eligible for any platinum-containing chemotherapy, or
- who have disease progression during or following platinum-containing chemotherapy or within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy.
Non-muscle Invasive Bladder CancerKEYTRUDA is indicated for the treatment of patients with Bacillus Calmette-Guerin (BCG)-unresponsive, high-risk, non-muscle invasive bladder cancer (NMIBC) with carcinoma in situ with or without papillary tumors who are ineligible for or have elected not to undergo cystectomy.Microsatellite Instability-High or Mismatch Repair Deficient CancerKEYTRUDA is indicated for the treatment of adult and pediatric patients with unresectable or metastatic microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) solid tumors that have progressed following prior treatment and who have no satisfactory alternative treatment options.This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials. The safety and effectiveness of KEYTRUDA in pediatric patients with MSI-H central nervous system cancers have not been established.Microsatellite Instability-High or Mismatch Repair Deficient Colorectal CancerKEYTRUDA is indicated for the treatment of patients with unresectable or metastatic MSI-H or dMMR colorectal cancer (CRC).Gastric CancerKEYTRUDA, in combination with trastuzumab, fluoropyrimidine- and platinum-containing chemotherapy, is indicated for the first-line treatment of patients with locally advanced unresectable or metastatic HER2-positive gastric or gastroesophageal junction (GEJ) adenocarcinoma.This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.Esophageal CancerKEYTRUDA is indicated for the treatment of patients with locally advanced or metastatic esophageal or gastroesophageal (GEJ) (tumors with epicenter 1 to 5 centimeters above the GEJ) carcinoma that is not amenable to surgical resection or definitive chemoradiation either:
- in combination with platinum- and fluoropyrimidine-based chemotherapy, or
- as a single agent after one or more prior lines of systemic therapy for patients with tumors of squamous cell histology that express PD-L1 (CPS ≥10) as determined by an FDA-approved test.
Cervical CancerKEYTRUDA, in combination with chemotherapy, with or without bevacizumab, is indicated for the treatment of patients with persistent, recurrent, or metastatic cervical cancer whose tumors express PD-L1 (CPS ≥1) as determined by an FDA-approved test.KEYTRUDA, as a single agent, is indicated for the treatment of patients with recurrent or metastatic cervical cancer with disease progression on or after chemotherapy whose tumors express PD-L1 (CPS ≥1) as determined by an FDA-approved test.Hepatocellular CarcinomaKEYTRUDA is indicated for the treatment of patients with hepatocellular carcinoma (HCC) who have been previously treated with sorafenib. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.Merkel Cell CarcinomaKEYTRUDA is indicated for the treatment of adult and pediatric patients with recurrent locally advanced or metastatic Merkel cell carcinoma (MCC). This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.Renal Cell CarcinomaKEYTRUDA, in combination with axitinib, is indicated for the first-line treatment of adult patients with advanced renal cell carcinoma (RCC).KEYTRUDA is indicated for the adjuvant treatment of patients with RCC at intermediate-high or high risk of recurrence following nephrectomy, or following nephrectomy and resection of metastatic lesions.Tumor Mutational Burden-High CancerKEYTRUDA is indicated for the treatment of adult and pediatric patients with unresectable or metastatic tumor mutational burden-high (TMB-H) [≥10 mutations/megabase] solid tumors, as determined by an FDA-approved test, that have progressed following prior treatment and who have no satisfactory alternative treatment options. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials. The safety and effectiveness of KEYTRUDA in pediatric patients with TMB-H central nervous system cancers have not been established.Cutaneous Squamous Cell CarcinomaKEYTRUDA is indicated for the treatment of patients with recurrent or metastatic cutaneous squamous cell carcinoma (cSCC) or locally advanced cSCC that is not curable by surgery or radiation.Triple-Negative Breast CancerKEYTRUDA is indicated for the treatment of patients with high-risk early-stage triple-negative breast cancer (TNBC) in combination with chemotherapy as neoadjuvant treatment, and then continued as a single agent as adjuvant treatment after surgery.KEYTRUDA, in combination with chemotherapy, is indicated for the treatment of patients with locally recurrent unresectable or metastatic TNBC whose tumors express PD-L1 (CPS ≥10) as determined by an FDA-approved test.
For more information, visit www.merck.com and connect with us on Twitter, Facebook, Instagram, YouTube and LinkedIn.
Please see Prescribing Information for KEYTRUDA (pembrolizumab) at http://www.merck.com/product/usa/pi_circulars/k/keytruda/keytruda_pi.pdf and Medication Guide for KEYTRUDA at http://www.merck.com/product/usa/pi_circulars/k/keytruda/keytruda_mg.pdf . Source: Merck & Co., Inc.
Merck’s Keytruda combined with chemotherapy could benefit thousands of breast cancer patients
The combination significantly reduces cancer recurrence by approximately 37% and reduces secondary breast cancer by 39%
https://seekingalpha.com/symbol/MRK
MRK Dividend History
https://www.nasdaq.com/market-activity/stocks/mrk/dividend-history
ADCETRIS (brentuximab vedotin) in combination with chemotherapy
ADCETRIS (brentuximab vedotin) in combination with chemotherapy
ADCETRIS (brentuximab vedotin) in combination with chemotherapy
ADCETRIS® Combination Significantly Improves Overall Survival in Newly Diagnosed Patients with Advanced Hodgkin Lymphoma
02/03/2022– Full Data from Phase 3 ECHELON-1 Clinical Trial to be Submitted for Presentation at Upcoming Medical Meeting –BOTHELL, Wash.--(BUSINESS WIRE)-- Seagen Inc. (Nasdaq:SGEN) today announced that the phase 3 ECHELON-1 clinical trial demonstrated a statistically significant improvement in overall survival (OS) (p=0.009) in patients with advanced classical Hodgkin lymphoma (cHL) following treatment with ADCETRIS (brentuximab vedotin) in combination with chemotherapy. With approximately six years median follow up, patients receiving ADCETRIS plus doxorubicin, vinblastine, and dacarbazine (A+AVD) in the frontline setting had a 41 percent reduction in the risk of death (HR 0.59; [95% CI: 0.396 to 0.879]) compared with patients receiving doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD). The safety profile of ADCETRIS was consistent with previous studies and no new safety signals were observed.“These groundbreaking results are important for patients with advanced classical Hodgkin lymphoma given that an improvement in overall survival has rarely been shown in frontline treatment of this disease,” said Roger Dansey, M.D., Chief Medical Officer at Seagen. “We look forward to presentation of the results at an upcoming medical meeting.”ECHELON-1 is an open-label, international, randomized, phase 3 trial evaluating the safety and efficacy of frontline ADCETRIS plus AVD versus ABVD in 1,334 adult patients with stage III or IV cHL. Patients were randomly assigned to receive A+AVD or ABVD intravenously on days 1 and 15 of each 28-day cycle for up to six cycles. OS is the key secondary endpoint of the trial. The primary endpoint, modified progression free survival, served as the basis for global regulatory approvals.Please see Important Safety Information, including BOXED WARNING, for ADCETRIS below.ADCETRIS is approved for certain types of relapsed or refractory Hodgkin lymphoma (HL) including previously untreated Stage III/IV cHL and previously untreated peripheral T-cell lymphoma (PTCL). It has received marketing authorization in more than 75 countries and is being evaluated globally in more than 70 corporate- and investigator-sponsored clinical trials across multiple settings in lymphoma and other diseases. About ADCETRIS
ADCETRIS is an antibody-drug conjugate (ADC) comprising an anti-CD30 monoclonal antibody attached by a protease-cleavable linker to a microtubule disrupting agent, monomethyl auristatin E (MMAE), utilizing Seagen’s proprietary technology. The ADC employs a linker system that is designed to be stable in the bloodstream but to release MMAE upon internalization into CD30-expressing cells.ADCETRIS is indicated for the treatment of adult patients with:
- previously untreated Stage III or IV classical Hodgkin lymphoma (cHL), in combination with doxorubicin, vinblastine, and dacarbazine,
- cHL at high risk of relapse or progression as post-autologous hematopoietic stem cell transplantation (auto-HSCT) consolidation,
- cHL after failure of auto-HSCT or failure of at least two prior multi-agent chemotherapy regimens in patients who are not auto-HSCT candidates,
- previously untreated systemic anaplastic large cell lymphoma (sALCL) or other CD30-expressing peripheral T-cell lymphomas (PTCL), including angioimmunoblastic T-cell lymphoma and PTCL not otherwise specified, in combination with cyclophosphamide, doxorubicin, and prednisone,
- sALCL after failure of at least one prior multi-agent chemotherapy regimen, and
- primary cutaneous anaplastic large cell lymphoma (pcALCL) or CD30-expressing mycosis fungoides who have received prior systemic therapy.
Seagen and Takeda are jointly developing ADCETRIS. Under the terms of the collaboration agreement, Seagen has U.S. and Canadian commercialization rights and Takeda has rights to commercialize ADCETRIS in the rest of the world. Seagen and Takeda are funding joint development costs for ADCETRIS on a 50:50 basis, except in Japan where Takeda is solely responsible for development costs.https://www.adcetris.com/
For more information on the company’s marketed products and robust pipeline, visit www.seagen.com and follow @SeagenGlobal on Twitter. 1 https://www.cancer.org/cancer/hodgkin-lymphoma.htmlView source version on businesswire.com: https://www.businesswire.com/news/home/20220203005330/en/ Source: Seagen Inc.
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