On October 20, 2023 Merck (NYSE: MRK), known as MSD outside of the United States and Canada, reported results from the Phase 3 KEYNOTE-671 trial evaluating KEYTRUDA, Merck’s anti-PD-1 therapy, as a perioperative treatment regimen, which includes treatment before surgery (neoadjuvant) and after surgery (adjuvant), for patients with resectable stage II, IIIA or IIIB non-small cell lung cancer (NSCLC) (Press release, Merck & Co, OCT 20, 2023, View Source [SID1234636181]). These late-breaking data are being presented for the first time today during a proffered paper session at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress 2023 (abstract #LBA56).
Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:
Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing
Schedule Your 30 min Free Demo!
At the trial’s prespecified second interim analysis with a median follow-up of 36.6 months (range, 18.8 to 62.0), neoadjuvant KEYTRUDA plus chemotherapy followed by KEYTRUDA as a single agent 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 neoadjuvant placebo plus chemotherapy followed by adjuvant placebo, 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 36-month OS rates were 71.3% for patients who received the KEYTRUDA-based regimen versus 64.0% for patients who received the chemotherapy-placebo regimen.
As previously announced, KEYNOTE-671 met the trial’s other dual primary endpoint of event-free survival (EFS) at the first interim analysis of the study. At this second interim analysis, the EFS benefit observed in the previous interim analysis was maintained and the KEYTRUDA arm improved median EFS by nearly two and half years compared to the placebo and chemotherapy arm (47.2 months [95% CI, 32.9-NR] versus 18.3 months [95% CI, 14.8-22.1], respectively; HR=0.59 [95% CI, 0.48-0.72]). The 36-month EFS rates were 54.3% for patients who received the KEYTRUDA-based regimen versus 35.4% for patients who received the chemotherapy-placebo regimen.
"The results of KEYNOTE-671 represent an important milestone in our fight to improve treatment outcomes for patients with surgically resectable non-small cell lung cancer. The addition of perioperative KEYTRUDA to the standard of chemotherapy followed by surgery reduced the risk of death by 28% compared to placebo," said Dr. Jonathan Spicer, Associate Professor of Surgery at the McGill University Health Center and KEYNOTE-671 investigator. "Non-small cell lung cancer is the leading cause of cancer-related death worldwide and this new regimen applies to a wide range of surgically resectable patients. Hence, the introduction of KEYTRUDA to the standard of care of these patients could be a powerful tool for healthcare professionals to help extend the lives of patients."
"With these unprecedented survival data from KEYNOTE-671, KEYTRUDA is the first and only anti-PD-1/L1 therapy to demonstrate a statistically significant improvement in overall survival as a neoadjuvant and adjuvant treatment compared to a placebo and chemotherapy regimen for resectable non-small cell lung cancer," said Dr. Marjorie Green, senior vice president and head of late-stage oncology, global clinical development, Merck Research Laboratories. "While KEYTRUDA has been established as a foundational treatment in certain advanced lung cancers, these overall survival results support the role of KEYTRUDA for patients with earlier stages of this disease, who are in need of new treatment options that may help them live longer."
Merck previously announced that, based on OS and EFS results from KEYNOTE-671, the U.S. Food and Drug Administration (FDA) approved KEYTRUDA 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.
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 and small cell lung cancer (SCLC) include KEYNOTE-671, KEYNOTE-091, KEYNOTE-867, KEYLYNK-012, KEYLYNK-013 and KEYVIBE-006.
As announced, data spanning more than 15 types of cancer are being presented from Merck’s broad oncology portfolio and investigational pipeline at ESMO (Free ESMO Whitepaper) Congress 2023.
Study design and additional data from KEYNOTE-671
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 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.
Treatment-related adverse events (TRAEs) that were Grade ≥3 occurred in 45.2% of patients who received the KEYTRUDA-based regimen and 37.8% of patients who received the chemotherapy-placebo regimen. Treatment-related adverse events led to discontinuation of all study treatment in 13.6% of patients who received the KEYTRUDA-based regimen and 5.3% of patients who received the chemotherapy-placebo regimen. Treatment-related AEs led to death in 1.0% of patients who received the KEYTRUDA-based regimen and 0.8% of patients who received the chemotherapy-placebo regimen. No new safety concerns were identified.
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 approximately 1.8 million deaths from lung cancer globally. Non-small cell lung cancer is the most common type of lung cancer, accounting for about 81% of all cases. In the U.S., the overall five-year survival rate for patients diagnosed with lung cancer is 25%, which is a 21% improvement over the last five years. Improved survival rates are due, in part, to advances in diagnostic and surgical procedures, as well as the introduction of new therapies. However, screening, early detection and improving treatment rates remain an important unmet need, as 44% of lung cancer cases are not found until they are advanced. Only 5.8% of people in the U.S. who are eligible were screened for lung cancer.