Merck (NYSE: MRK) has discontinued the vibostolimab and pembrolizumab coformulation arm of the Phase 3 KeyVibe-010 trial after a pre-planned analysis indicated it was unlikely to meet its primary endpoint of recurrence-free survival (RFS) in patients with resected high-risk melanoma (Stage IIB-IV). The decision, based on the recommendation of an independent Data Monitoring Committee (DMC), prompts a shift to KEYTRUDA monotherapy for patients in the coformulation arm.
The KeyVibe-010 trial (NCT05665595) was a randomized, double-blind, active comparator-controlled study evaluating the coformulation of vibostolimab (anti-TIGIT antibody) and pembrolizumab (KEYTRUDA, anti-PD-1 therapy) versus KEYTRUDA alone as adjuvant treatment. The trial enrolled 1594 patients who were randomly assigned (1:1) to receive either the vibostolimab/pembrolizumab coformulation or pembrolizumab monotherapy.
Futility Analysis and Discontinuation
Data from the pre-planned analysis revealed that the coformulation arm did not meet the pre-specified futility criteria for RFS. Furthermore, a higher rate of discontinuation of all adjuvant therapy was observed in the coformulation arm compared to the KEYTRUDA-only arm, primarily due to immune-mediated adverse experiences. This higher discontinuation rate made it highly improbable that the trial could achieve a statistically significant improvement in RFS.
Dr. Marjorie Green, senior vice president and head of oncology, global clinical development, Merck Research Laboratories, stated, "Through our clinical development program, we continue to ask the tough questions in an effort to fully explore the potential of novel coformulations and combinations that build on the foundation of KEYTRUDA, with a goal to improve upon current standards of care and help even more patients with cancer."
Ongoing Studies and Future Directions
Despite the setback with KeyVibe-010, Merck remains committed to developing new treatment options for melanoma. The company is actively pursuing other avenues, including the ongoing Phase 3 V940-001 study in collaboration with Moderna. This study evaluates V940 (mRNA-4157), an investigational individualized neoantigen therapy (INT), in combination with KEYTRUDA as adjuvant treatment in patients with resected high-risk melanoma.
Additionally, Merck is evaluating the vibostolimab and pembrolizumab coformulation in several Phase 3 lung cancer trials (KeyVibe-003, KeyVibe-006, KeyVibe-007, and KeyVibe-008). Interim external data monitoring committee safety reviews have not resulted in any safety-related study modifications to date, and no changes to these studies are anticipated based on the KeyVibe-010 findings.
About Vibostolimab and KEYTRUDA
Vibostolimab (MK-7684) is an investigational humanized anti-TIGIT antibody designed to restore antitumor activity by blocking the TIGIT receptor from binding to its ligands (CD112 and CD155), thereby activating T lymphocytes that help destroy tumor cells. KEYTRUDA (pembrolizumab) is an anti-programmed death receptor-1 (PD-1) therapy that enhances the body’s immune system to detect and fight tumor cells by blocking the interaction between PD-1 and its ligands, PD-L1 and PD-L2.
Melanoma Context
Melanoma, the most serious form of skin cancer, is characterized by the uncontrolled growth of pigment-producing cells. Worldwide, there were more than 330,000 new cases diagnosed in 2022. In the U.S., it is estimated that there will be more than 100,000 new cases of melanoma diagnosed and more than 8,000 deaths resulting from the disease in 2024.
