Merck Updates on Phase 3 Trial of Vibostolimab and Pembrolizumab in Small Cell Lung Cancer

Merck, operating as MSD outside the United States and Canada, declared the termination of its Phase 3 KeyVibe-008 trial. This decision followed the counsel of an independent Data Monitoring Committee (DMC). The trial was focused on an investigational fixed-dose combination of vibostolimab, an anti-TIGIT antibody, and pembrolizumab (KEYTRUDA®), Merck’s anti-PD-1 therapy, paired with chemotherapy. This combination was compared to atezolizumab with chemotherapy, aimed at first-line treatment of patients with extensive-stage small cell lung cancer (ES-SCLC).

During a pre-planned analysis, the data indicated that the primary endpoint of overall survival (OS) did not meet the expected criteria. Moreover, patients receiving the vibostolimab and pembrolizumab combination experienced a higher rate of adverse events and immune-related adverse events compared to those in the control group. A thorough analysis of the study is underway.

Merck has informed study investigators of this outcome, advising that patients halt ongoing treatment with the combination of vibostolimab and pembrolizumab and instead consider atezolizumab. The results are anticipated to be shared with the scientific community.

Dr. Marjorie Green, Senior Vice President and Head of Oncology, Global Clinical Development at Merck Research Laboratories, noted the grave challenges posed by small cell lung cancer, highlighted by its meager seven percent five-year survival rate and limited advancements in treatment. Emphasizing the importance of innovative research, Dr. Green reaffirmed Merck’s commitment to exploring new treatment avenues for this debilitating disease, expressing gratitude to all participants in the study.

Merck continues to pursue an extensive clinical development program in lung cancer, advancing multiple registration-enabling studies focused on earlier stages of the disease and novel combinations. In collaboration with Daiichi Sankyo, Merck recently started the IDeate-Lung02 Phase 3 trial, investigating the efficacy and safety of ifinatamab deruxtecan (I-DXd) for patients with relapsed SCLC compared to chemotherapy.

Additionally, Merck and Daiichi Sankyo expanded their global co-development and co-commercialization agreement to include Merck’s MK-6070, an investigational delta-like ligand 3 (DLL3) targeting T-cell engager currently in a Phase 1/2 trial. Plans are underway to evaluate MK-6070 in combination with I-DXd for specific SCLC patients and explore other potential combinations. Merck acquired MK-6070 as part of its acquisition of Harpoon Therapeutics.

Ongoing Phase 3 studies involving the vibostolimab and pembrolizumab fixed-dose combination in lung cancer, which are regularly monitored by external data committees, include KeyVibe-003, KeyVibe-006, and KeyVibe-007. So far, safety reviews have not necessitated any modifications to these studies, which continue to undergo comprehensive safety monitoring.

KeyVibe-008 is a randomized, double-blind Phase 3 trial evaluating a fixed-dose combination of vibostolimab and pembrolizumab with etoposide and platinum chemotherapy, compared to atezolizumab with the same chemotherapy regimen for first-line treatment of ES-SCLC patients. The trial’s primary endpoint is overall survival, with secondary endpoints including progression-free survival, objective response rate, and duration of response, all assessed by blinded independent central review (BICR). The study enrolled 460 patients, randomized equally to either treatment group.

Lung cancer remains the leading cause of cancer mortality globally, with approximately 2.48 million new cases and 1.8 million deaths recorded in 2022 alone. The overall five-year survival rate for lung cancer patients in the United States is 25%. Early detection and screening, smoking reduction, advanced diagnostic and surgical procedures, and new therapies have all contributed to improved survival rates. Small cell lung cancer accounts for about 15% of all lung cancers and is particularly aggressive, with a five-year survival rate of just 7% in the United States. Early detection and screening are critical, as 44% of lung cancer cases are diagnosed at advanced stages.

Merck is committed to transforming lung cancer treatment through extensive research efforts aimed at improving patient outcomes. With nearly 200 clinical trials involving over 36,000 patients worldwide, Merck is leading the charge in lung cancer research. KEYTRUDA has six approved indications in the U.S. and is approved in over 95 countries, with ongoing trials exploring its use in earlier stages of lung cancer and in combination with other treatments.

Vibostolimab, discovered and developed by Merck, is an investigational anti-TIGIT antibody designed to enhance antitumor activity by blocking the TIGIT receptor, thus activating T lymphocytes to target tumor cells. The fixed-dose combination of vibostolimab and pembrolizumab is being tested across various cancers, including lung cancer, other solid tumors, and blood cancers.

KEYTRUDA, an anti-PD-1 therapy, enhances the body's immune response against tumor cells. It is part of Merck's largest immuno-oncology clinical research program, with over 1,600 trials across a variety of cancers and treatment settings. The program aims to understand the role of KEYTRUDA in different cancers and identify biomarkers that predict patient response to the treatment. KEYTRUDA is not approved for treating SCLC.