RAHWAY, N.J. - Merck (NYSE: MRK), known as MSD outside the United States and Canada, announced the U.S. Food and Drug Administration (FDA) has accepted for review a new supplemental Biologics License Application (sBLA) seeking approval for KEYTRUDA for the adjuvant treatment of patients with stage IB (?4 centimeters), II or IIIA non-small cell lung cancer (NSCLC) following complete surgical resection. The sBLA is based on data from the pivotal Phase 3 KEYNOTE-091 trial, also known as EORTC-1416-LCG/ETOP-8-15 - PEARLS, conducted in collaboration with the European Organisation for Research and Treatment of Cancer (EORTC) and the European Thoracic Oncology Platform (ETOP). The FDA has set a Prescription Drug User Fee Act (PDUFA), or target action, date of January 29, 2023, however, further data may be provided during the review process that may delay this date.
The study has dual primary endpoints of disease-free survival (DFS) regardless of PD-L1 expression and DFS in patients whose tumors express PD-L1 (tumor proportion score [TPS] ?50%). At the interim analysis of this study, adjuvant treatment with KEYTRUDA demonstrated a significant improvement in DFS for patients regardless of PD-L1 expression compared to placebo. Disease-free survival in patients whose tumors express PD-L1 (TPS ?50%) did not reach statistical significance per the pre-specified statistical plan. The trial will continue to analyze DFS in patients whose tumors express high levels of PD-L1 (TPS ?50%) as well as other secondary endpoints. The safety profile of KEYTRUDA in this study was consistent with that observed in previously reported studies. Results were recently presented at a European Society for Medical Oncology (ESMO) Virtual Plenary.
'KEYTRUDA is foundational in the treatment of metastatic non-small cell lung cancer. The acceptance of our application demonstrates the progress we are making in earlier lines and earlier stages of certain cancers across our oncology portfolio,' said Dr. Eliav Barr, senior vice president, head of global clinical development and chief medical officer, Merck Research Laboratories. 'If approved, KEYTRUDA would be the first adjuvant immunotherapy-based option in the U.S. for patients with stage IB (?4 centimeters) to IIIA non-small cell lung cancer following surgical resection regardless of PD-L1 expression.'
In addition to KEYNOTE-091, six 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; KEYNOTE-629 in cutaneous squamous cell carcinoma; and KEYNOTE-057 in Bacillus Calmette-Guerin-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, KEYLYNK-012 and KEYVIBE-006.
About KEYNOTE-091
KEYNOTE-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 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.
About lung cancer
Lung cancer is the leading cause of cancer death worldwide. In 2020 alone, there were more than 2.2 million new cases and 1.8 million deaths from lung cancer globally. Non-small cell lung cancer is the most common type of lung cancer, accounting for about 82% of all cases. In the U.S., the overall five-year survival rate for patients diagnosed with lung cancer is 24%, a 14% improvement over the last five years. Improving survival rates are due in part to earlier detection and screening, reduction in smoking, advances in diagnostic and surgical procedures as well as the introduction of new therapies.
About Merck's research in lung cancer
Merck is advancing research aimed at transforming the way lung cancer is treated, with a goal of improving outcomes for patients affected by this deadly disease. Through nearly 200 clinical trials evaluating more than 36,000 patients around the world, Merck is at the forefront of lung cancer research. In advanced NSCLC, KEYTRUDA has four approved U.S. indications (see indications below) and is approved in advanced NSCLC in more than 95 countries. Among Merck's research efforts are trials focused on evaluating KEYTRUDA in earlier stages of lung cancer as well as identifying new combinations and coformulations with KEYTRUDA.
About Merck's early-stage cancer clinical program
Finding cancer at an earlier stage may give patients a greater chance of long-term survival. Many cancers are considered most treatable and potentially curable in their earliest stage of disease. Building on the strong understanding of the role of KEYTRUDA in later-stage cancers, Merck is studying KEYTRUDA in earlier disease states, with approximately 20 ongoing registrational studies across multiple types of cancer.
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.
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 Merck
At Merck, known as MSD outside of the United States and Canada, we are unified around our purpose: We use the power of leading-edge science to save and improve lives around the world. For more than 130 years, we have brought hope to humanity through the development of important medicines and vaccines. We aspire to be the premier research-intensive biopharmaceutical company in the world - and today, we are at the forefront of research to deliver innovative health solutions that advance the prevention and treatment of diseases in people and animals. We foster a diverse and inclusive global workforce and operate responsibly every day to enable a safe, sustainable and healthy future for all people and communities. For more information, visit www.merck.com and connect with us on Twitter, Facebook, Instagram, YouTube and LinkedIn.
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