RAHWAY, N.J. – Merck (NYSE: MRK), known as MSD outside of the United States and Canada, today announced that the European Commission (EC) has approved KEYTRUDA, Merck’s anti-PD-1 therapy, in combination with platinum-containing chemotherapy as neoadjuvant treatment, then continued as monotherapy as adjuvant treatment, for resectable non-small cell lung cancer (NSCLC) at high risk of recurrence in adults.
This approval by the EC follows the positive recommendation from the Committee for Medicinal Products for Human Use received in February 2024 and was based on results from the Phase 3 KEYNOTE-671 trial. At a median follow-up of 29.8 months (range, 0.4 to 62.0 months), KEYTRUDA plus chemotherapy in the neoadjuvant setting followed by KEYTRUDA as monotherapy after surgical resection significantly improved overall survival (OS), reducing the risk of death by 28% (HR=0.72 [95% CI, 0.56-0.93]; one-sided p=0.00517) in patients with resectable stage II, IIIA or IIIB NSCLC versus placebo plus chemotherapy in the neoadjuvant setting followed by placebo after surgical resection, regardless of PD-L1 expression. For patients who received the KEYTRUDA-based regimen, median OS was not reached (95% CI, NR-NR) versus 52.4 months (95% CI, 45.7-NR) for patients who received the chemotherapy-placebo regimen. The KEYTRUDA-based regimen also improved event-free survival (EFS), reducing the risk of disease recurrence, progression or death by 41% (HR=0.59 [95% CI, 0.48-0.72]) compared to the chemotherapy-placebo regimen. For patients who received the KEYTRUDA-based regimen, median EFS was improved by nearly two and a half years compared to the chemotherapy-placebo regimen (47.2 months [95% CI, 32.9-NR] versus 18.3 months [95% CI, 14.8-22.1], respectively).
“Despite the clinical advances for patients with metastatic lung cancer, lung cancer continues to be the leading cause of cancer death in Europe, reinforcing the need to treat these patients in earlier stages of their disease, where we may have the most impact,” said Dr. Solange Peters, chair of the medical oncology and thoracic malignancies department, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland. “The approval of this KEYTRUDA-based regimen is an important milestone for patients diagnosed with resectable non-small cell lung cancer at high risk of recurrence, regardless of PD-L1 expression, providing a new option for these patients that has shown, through the results of the Phase 3 KEYNOTE-671 trial, the potential to help extend their lives.”
This approval allows marketing of this KEYTRUDA regimen for this indication in all 27 EU member states, as well as Iceland, Liechtenstein, Norway and Northern Ireland. KEYTRUDA is now approved for six indications in NSCLC, and for 27 indications overall in the EU. In October 2023, KEYTRUDA was approved in the U.S. for the treatment of patients with resectable (tumors ≥4 cm or node positive) NSCLC in combination with platinum-containing chemotherapy as neoadjuvant treatment, and then continued as a single agent as adjuvant treatment after surgery.
“Today’s approval of the first anti-PD-1/L1 therapy as part of a treatment regimen in Europe for the neoadjuvant followed by adjuvant treatment of resectable NSCLC based on positive overall survival results demonstrates our continued progress to advance treatments in earlier stages of lung cancer,” said Marjorie Green, senior vice president and head of oncology, global clinical development, Merck Research Laboratories. “We are eager to build on this momentum as we plan to seek additional approvals of this regimen around the world, and to work together with the cancer community to help drive earlier diagnoses of lung cancer, an urgent need.”
About the KEYNOTE-671 study design
KEYNOTE-671 is a randomized, double-blind Phase 3 trial (ClinicalTrials.gov, NCT03425643) evaluating KEYTRUDA in combination with neoadjuvant chemotherapy, followed by surgery and continued adjuvant treatment with KEYTRUDA as a single agent, versus placebo plus neoadjuvant chemotherapy, followed by resection and adjuvant placebo, in patients with resectable stage II, IIIA or IIIB (T3-4N2) NSCLC (per the eight edition of the American Joint Committee on Cancer [AJCC] Cancer Staging Manual). The trial’s dual primary endpoints are EFS, per RECIST v1.1 by investigator assessment, and OS. Key secondary endpoints include pathologic complete response (pCR) and major pathological response (mPR). The study enrolled 797 patients who were randomly assigned (1:1) to receive either:
- KEYTRUDA (200 mg intravenously [IV] every three weeks [Q3W]) plus chemotherapy (cisplatin [75 mg/m2, IV; given on Day 1 of each cycle] and either gemcitabine [1,000 mg/m2, IV; given on Days 1 and 8 of each cycle] or pemetrexed [500 mg/m2, IV; given on Day 1 of each cycle]) for up to four cycles as neoadjuvant therapy prior to surgery. Within 4-12 weeks following surgery, KEYTRUDA (200 mg) was administered every three weeks for up to 13 cycles, or;
- Placebo (saline IV Q3W) plus chemotherapy (cisplatin [75 mg/m2, IV; given on Day 1 of each cycle] and either gemcitabine [1,000 mg/m2, IV; given on Days 1 and 8 of each cycle] or pemetrexed [500 mg/m2, IV; given on Day 1 of each cycle]) for up to four cycles as neoadjuvant therapy prior to surgery. Within 4‑12 weeks following surgery, placebo was administered every three weeks for up to 13 cycles.
About lung cancer
Lung cancer is the leading cause of cancer death worldwide. In 2022 alone, there were approximately 2.4 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 80% of all cases. In recent decades, the overall five-year survival rate for patients diagnosed with lung cancer increased from 11% to 15% on average across EU countries. Improved 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. Early detection and screening remain an important unmet need, as 44% of lung cancer cases are not found until they are advanced.
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 NSCLC, KEYTRUDA has six approved U.S. indications (see indications below) and is approved for advanced disease 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 more than 25 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 1,600 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.
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.
Media Contacts
Julie Cunningham
+1 (617) 519-6264
Sienna Choi
+1 (908) 873-4311
Investor Contacts
Peter Dannenbaum
+1 (732) 594-1579
Damini Chokshi
+1 (732) 594-1577