KENILWORTH, N.J.–(BUSINESS WIRE) October 30, 2018 –Merck (NYSE: MRK), known as MSD outside the United States and Canada, today announced that the U.S. Food and Drug Administration (FDA) has approved Keytruda, Merck’s anti-PD-1 therapy, in combination with carboplatin and either paclitaxel or nab-paclitaxel, for the first-line treatment of patients with metastatic squamous non-small cell lung cancer (NSCLC) based on results from the KEYNOTE-407 trial. In the pivotal Phase 3 trial of patients regardless of tumor PD-L1 expression status, Keytruda in combination with chemotherapy (carboplatin and either paclitaxel or nab-paclitaxel) significantly improved overall survival (OS), reducing the risk of death by 36 percent compared to chemotherapy alone (HR=0.64 [95% CI, 0.49, 0.85]; p=0.0017). This approval marks the first time an anti-PD-1 regimen has been approved for the first-line treatment of squamous NSCLC regardless of tumor PD-L1 expression status.
“Today’s approval expands our current lung cancer indications to include combination treatment in patients with squamous cell carcinoma, a type of lung cancer that is particularly difficult to treat,” said Dr. Roger M. Perlmutter, president, Merck Research Laboratories. “Approval by the FDA has the potential to mean that Keytruda can be used to improve survival for more patients with this debilitating disease.”
Immune-mediated adverse reactions, which may be severe or fatal, can occur with Keytruda, including pneumonitis, colitis, hepatitis, endocrinopathies, nephritis, severe skin reactions, solid organ transplant rejection, and complications of allogeneic hematopoietic stem cell transplantation (HSCT). Based on the severity of the adverse reaction, Keytruda should be withheld or discontinued and corticosteroids administered if appropriate. Keytruda can also cause severe or life-threatening infusion-related reactions. Based on its mechanism of action, Keytruda can cause fetal harm when administered to a pregnant woman.
“The results that support this approval from the KEYNOTE-407 trial demonstrate the potential of Keytruda in combination with chemotherapy in patients with squamous non-small cell lung cancer, regardless of PD-L1 expression,” said Dr. Balazs Halmos, director of the multidisciplinary thoracic oncology program at the Montefiore Einstein Center for Cancer Care and director of clinical cancer genomics at the Albert Einstein College of Medicine. “With this important approval, more patients will have the opportunity to benefit from immunotherapy.”
Keytruda is the first anti-PD-1 approved in the first-line setting as both combination and monotherapy in certain patients with metastatic NSCLC. With this approval, all appropriate patients with metastatic squamous NSCLC and all appropriate patients with metastatic nonsquamous NSCLC and no EGFR or ALK genomic tumor aberrations are now eligible for a Keytruda-based regimen as their first-line treatment option.
Data Supporting the Approval
The approval was based on data from KEYNOTE-407, a randomized, double-blind, multicenter, placebo-controlled study. The key eligibility criteria for this study were metastatic squamous NSCLC, regardless of tumor PD-L1 expression status, and no prior systemic treatment for metastatic disease. Patients with autoimmune disease that required systemic therapy within two years of treatment; a medical condition that required immunosuppression; or who had received more than 30 Gy of thoracic radiation within the prior 26 weeks were ineligible. Patients were randomized to receive Keytruda 200 mg and carboplatin every three weeks for four cycles, plus paclitaxel every three weeks for four cycles or nab-paclitaxel on Days 1, 8 and 15 of every three-week cycle for four cycles, followed by Keytruda 200 mg every three weeks; or placebo and carboplatin every three weeks for four cycles, plus paclitaxel every three weeks for four cycles or nab-paclitaxel on Days 1, 8 and 15 of every three-week cycle for four cycles, followed by placebo every three weeks.
Treatment with Keytruda or placebo continued until progression of disease, unacceptable toxicity, or a maximum of 24 months. Patients in the placebo arm were offered Keytruda as a single agent at the time of disease progression.
Primary efficacy outcome measures were OS as well as progression-free survival (PFS) and objective response rate (ORR) as assessed by blinded independent central review (BICR) using RECIST v1.1, modified to follow a maximum of 10 target lesions and a maximum of five target lesions per organ. An additional efficacy outcome measure was duration of response.
In KEYNOTE-407, there was a statistically significant improvement in OS, PFS and ORR in patients randomized to Keytruda in combination with carboplatin and either paclitaxel or nab-paclitaxel compared with patients randomized to placebo with carboplatin and either paclitaxel or nab-paclitaxel.
Safety and Efficacy Results in KEYNOTE-407
|Number of events (%)||85 (31%)||120 (43%)|
|Median in months (95% CI)||15.9 (13.2, NE)||11.3 (9.5, 14.8)|
|Hazard ratio* (95% CI)||0.64 (0.49, 0.85)|
|Number of events (%)||152 (55%)||197 (70%)|
|Median in months (95% CI)||6.4 (6.2, 8.3)||4.8 (4.3, 5.7)|
|Hazard ratio* (95% CI)||0.56 (0.45, 0.70)|
|Overall Response Rate ‡|
|Overall response rate (95% CI)||58% (48, 68)||35% (26, 45)|
|Difference (95% CI)||23.6% (9.9, 36.4)|
|Duration of Response ‡|
|Median duration of response in months (range)||7.2 (2.4, 12.4+)||4.9 (2.0, 12.4+)|
* Based on the stratified Cox proportional hazard model
† Based on a stratified log-rank test
‡ ORR primary analysis and DOR analysis were conducted with the first 204 patients enrolled.
§ Based on a stratified Miettinen-Nurminen test
|NE = not estimable|
In KEYNOTE-407, safety data are available for the first 203 patients who received Keytruda and chemotherapy (n=101) or placebo and chemotherapy (n=102). The safety of Keytruda in combination with carboplatin and either paclitaxel or nab-paclitaxel was investigated in 101 patients at the first interim analysis of KEYNOTE-407. Keytruda was discontinued for adverse reactions in 15 percent of patients with no single type of adverse reaction accounting for the majority. Adverse reactions leading to interruption of Keytruda occurred in 43 percent of patients; the most common (≥2%) were thrombocytopenia (20%) and neutropenia (11%), anemia (6%), asthenia (2%), and diarrhea (2%). The most frequent (≥2%) serious adverse reactions were febrile neutropenia (6%), pneumonia (6%), and urinary tract infection (3%). The most common adverse reactions (≥20%) with Keytruda in combination with chemotherapy were fatigue/asthenia, nausea, constipation, diarrhea, decreased appetite, rash, vomiting, cough, dyspnea, pyrexia, alopecia, and peripheral neuropathy.
About Keytruda (pembrolizumab) Injection, 100mg
Keytruda is an anti-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 850 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.
Merck’s Focus on Cancer
Our goal is to translate breakthrough science into innovative oncology medicines to help people with cancer worldwide. At Merck, the potential to bring new hope to people with cancer drives our purpose and supporting accessibility to our cancer medicines is our commitment. As part of our focus on cancer, Merck is committed to exploring the potential of immuno-oncology with one of the largest development programs in the industry across more than 30 tumor types. We also continue to strengthen our portfolio through strategic acquisitions and are prioritizing the development of several promising oncology candidates with the potential to improve the treatment of advanced cancers. For more information about our oncology clinical trials, visit www.merck.com/clinicaltrials.
About the Merck Access Program for Keytruda
At Merck, we are committed to supporting accessibility to our cancer medicines. Merck provides multiple programs to help ensure that appropriate patients who are prescribed Keytruda have access to our anti-PD-1 therapy. The Merck Access Program provides reimbursement support for patients receiving Keytruda, including information to help with out-of-pocket costs and co-pay assistance for eligible patients. Merck also offers free product through our patient assistance program to eligible patients, primarily the uninsured, who, without our assistance, could not afford their medicine. More information is available by calling 855-257-3932 or visiting www.merckaccessprogram-keytruda.com .
About Merck’s Patient Support Program for Keytruda
Merck is committed to helping provide patients and their caregivers support throughout their treatment with Keytruda. The KEY+YOU Patient Support Program provides a range of resources and services. For further information and to sign up, patients and physicians may call 85-KEYTRUDA (855-398-7832) or visit www.keytruda.com.
For more than a century, Merck, a leading global biopharmaceutical company known as MSD outside of the United States and Canada, has been inventing for life, bringing forward medicines and vaccines for many of the world’s most challenging diseases. Through our prescription medicines, vaccines, biologic therapies and animal health products, we work with customers and operate in more than 140 countries to deliver innovative health solutions. We also demonstrate our commitment to increasing access to health care through far-reaching policies, programs and partnerships. Today, Merck continues to be at the forefront of research to advance the prevention and treatment of diseases that threaten people and communities around the world – including cancer, cardio-metabolic diseases, emerging animal diseases, Alzheimer’s disease and infectious diseases including HIV and Ebola. For more information, visit www.merck.com and connect with us on Twitter, Facebook, Instagram, YouTube and LinkedIn.
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Posted: October 2018
- FDA Approves Expanded Label for Merck’s Keytruda (pembrolizumab) in Patients with Metastatic Nonsquamous NSCLC with No EGFR or ALK Genomic Tumor Aberrations – August 21, 2018
- FDA Approves Keytruda (pembrolizumab) for Treatment of Refractory or Relapsed Primary Mediastinal Large B-Cell Lymphoma (PMBCL) – June 13, 2018
- FDA Approves Keytruda (pembrolizumab) for Previously Treated Patients with Recurrent or Metastatic Cervical Cancer Whose Tumors Express PD-L1 – June 12, 2018
- FDA Approves Merck’s Keytruda (pembrolizumab) for Previously Treated Patients with Recurrent Locally Advanced or Metastatic Gastric or Gastroesophageal Junction Cancer Whose Tumors Express PD-L1 – September 22, 2017
- FDA Approves Keytruda (pembrolizumab) as First Cancer Treatment for any Solid Tumor with a Specific Genetic Feature – May 23, 2017
- FDA Approves Merck’s Keytruda (pembrolizumab) for Certain Patients with Locally Advanced or Metastatic Urothelial Carcinoma – May 18, 2017
- FDA Approves Merck’s Keytruda (pembrolizumab) as First-Line Combination Therapy for Patients with Metastatic Nonsquamous Non-Small Cell Lung Cancer (NSCLC), Irrespective of PD-L1 Expression – May 10, 2017
- FDA Approves Merck’s Keytruda (pembrolizumab) for Classical Hodgkin Lymphoma (cHL) – March 15, 2017
- FDA Approves Merck’s Keytruda (pembrolizumab) for First-Line Treatment of Certain Patients with Metastatic Non-Small Cell Lung Cancer – October 24, 2016
- FDA Approves Merck’s Keytruda (pembrolizumab) for Patients with Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma – August 5, 2016
- FDA Approves Expanded Indication for Keytruda (pembrolizumab) for the Treatment of Patients with Advanced Melanoma – December 18, 2015
- FDA Approves Keytruda (pembrolizumab) for Advanced Non-Small Cell Lung Cancer – October 2, 2015
- FDA Approves Keytruda (pembrolizumab) for Advanced Melanoma – September 4, 2014
- Merck to Present New Data in Five Tumor Types from Studies Evaluating Pembrolizumab – September 2, 2014
- Merck’s Investigational Anti-PD-1 Antibody, Pembrolizumab, Under Regulatory Review in Europe for Advanced Melanoma – June 30, 2014
Keytruda (pembrolizumab) FDA Approval History