Merck Updates on KeyVibe and KEYFORM Trials for Vibostolimab and Favezelimab with Pembrolizumab

RAHWAY, N.J.--Merck, recognized as MSD outside the United States and Canada, made a significant announcement on December 16, 2024, regarding the discontinuation of its clinical development programs for two investigational antibodies: vibostolimab and favezelimab. Vibostolimab, an anti-TIGIT antibody, was being explored in combination with pembrolizumab (KEYTRUDA) under the KeyVibe program, while favezelimab, an anti-LAG-3 antibody, was paired with pembrolizumab in the KEYFORM program.

Merck has chosen to end Phase 3 trials KeyVibe-003 and KeyVibe-007, which were assessing the efficacy of the combination of vibostolimab and pembrolizumab in specific patients with non-small cell lung cancer (NSCLC). This decision followed the recommendation of an independent Data Monitoring Committee (DMC), which, through a pre-planned analysis, found that both trials met the pre-specified futility criteria for overall survival, the primary endpoint. Despite the anticipated increase in immune-related adverse events with the dual therapy, no new safety concerns emerged. Upon reviewing all data from the Phase 3 KeyVibe studies, Merck also decided to discontinue the Phase 3 KeyVibe-006 trial and other related studies involving vibostolimab.

In a separate strategic move, Merck has opted to terminate the development of favezelimab, halting enrollment in the Phase 3 KEYFORM-008 trial. This trial was examining the combination of favezelimab and pembrolizumab in patients with relapsed or refractory classical Hodgkin lymphoma (cHL) who had previously undergone anti-PD-1 therapy. Current participants will be allowed to continue treatment until the trial concludes. The decision to end the favezelimab program follows a comprehensive evaluation of existing data and reflects Merck’s intention to focus on other promising candidates within its oncology pipeline. It is important to note that this decision was not motivated by safety concerns regarding the drug combination.

Merck is actively communicating with investigators involved in these trials, advising patients to discuss future steps and treatment options with their study teams and healthcare providers. Although data analyses for the Phase 3 trials are still ongoing, Merck plans to share the findings with the broader scientific community.

Dr. Marjorie Green, Senior Vice President and Head of Oncology, Global Clinical Development at Merck Research Laboratories, expressed gratitude to all participants and researchers who contributed to these studies. She emphasized that the discontinuation reflects Merck’s commitment to prioritizing projects with the highest potential to enhance cancer treatment outcomes.

The KeyVibe-003 trial was a randomized, double-blind Phase 3 study evaluating the combination of vibostolimab and pembrolizumab versus pembrolizumab alone as a first-line treatment for patients with PD-L1 positive metastatic NSCLC. It focused on overall survival and included secondary endpoints like progression-free survival and overall response rate.

KeyVibe-007 was another randomized, double-blind Phase 3 trial exploring the combination of vibostolimab and pembrolizumab with chemotherapy in treatment-naïve metastatic NSCLC patients. It aimed to assess overall survival and other endpoints such as safety and patient-reported outcomes.

Meanwhile, the KEYFORM-008 trial was a randomized, open-label Phase 3 study assessing the combination of favezelimab and pembrolizumab against physician’s choice chemotherapy for patients with PD-1 relapsed or refractory cHL. The primary goal was progression-free survival as per the Lugano Response Criteria evaluated by Blinded Independent Central Review.

Vibostolimab and favezelimab were both investigational antibodies developed by Merck, targeting specific immune receptors to enhance T cell response against tumor cells. Despite halting their development, Merck continues to harness its extensive oncology pipeline to pursue treatments that offer significant benefits to cancer patients.