Merck Discontinues Phase 3 KeyVibe-008 Trial of Vibostolimab and Pembrolizumab in Extensive-Stage Small Cell Lung Cancer
Key Insights
Merck (search) halted the Phase 3 KeyVibe-008 trial after an independent review showed the vibostolimab/pembrolizumab combination with chemotherapy did not meet futility criteria for overall survival in ES-SCLC.
Patients receiving the vibostolimab and pembrolizumab fixed-dose combination experienced a higher rate of adverse events and immune-related adverse events compared to the control arm.
The trial evaluated vibostolimab, an anti-TIGIT (search) antibody, combined with pembrolizumab (KEYTRUDA®), an anti-PD-1 (search) therapy, plus chemotherapy versus atezolizumab plus chemotherapy as a first-line treatment.
Merck (search) has announced the discontinuation of the Phase 3 KeyVibe-008 trial evaluating the investigational fixed-dose combination of vibostolimab and pembrolizumab in patients with extensive-stage small cell lung cancer (search) (ES-SCLC). The decision was based on the recommendation of an independent Data Monitoring Committee (DMC) after a pre-planned analysis revealed that the primary endpoint of overall survival (OS) met the pre-specified futility criteria. Furthermore, patients in the vibostolimab and pembrolizumab arm experienced a higher rate of adverse events (AEs) and immune-related AEs compared to the control arm.
The KeyVibe-008 trial (NCT05224141) was a randomized, double-blind study designed to compare the efficacy and safety of a fixed-dose combination of vibostolimab and pembrolizumab (MK-7684A) in combination with etoposide and platinum chemotherapy versus atezolizumab in combination with etoposide and platinum chemotherapy as a first-line treatment for ES-SCLC. The primary endpoint was overall survival (OS), with key secondary endpoints including progression-free survival, objective response rate, and duration of response, all assessed by blinded independent central review (BICR). The trial enrolled 460 patients who were randomized (1:1) to receive either the vibostolimab/pembrolizumab combination or atezolizumab, both in combination with chemotherapy.
Impact on SCLC Treatment Landscape
Small cell lung cancer (search) (SCLC) is a particularly aggressive form of lung cancer, accounting for approximately 15% of all lung cancer cases. Patients with ES-SCLC face a poor prognosis, with an estimated five-year survival rate of only 7% in the United States. The current standard of care typically involves chemotherapy, often in combination with immune checkpoint inhibitors like atezolizumab. The discontinuation of KeyVibe-008 highlights the challenges in improving outcomes for this patient population.
Ongoing Research and Future Directions
Despite the setback with KeyVibe-008, Merck (search) remains committed to advancing research in lung cancer. The company has an extensive clinical development program, including multiple registration-enabling studies focused on earlier stages of disease and novel combinations. Merck is also collaborating with Daiichi Sankyo to evaluate ifinatamab deruxtecan (I-DXd) in a Phase 3 trial (IDeate-Lung02) for relapsed SCLC. Additionally, the companies are planning to evaluate MK-6070, a DLL3 (search)-targeting T-cell engager, in combination with I-DXd in certain patients with SCLC.
Vibostolimab and Pembrolizumab
Vibostolimab (MK-7684) is an investigational humanized anti-TIGIT (search) antibody designed to restore antitumor activity by blocking the TIGIT receptor from binding to its ligands, thereby activating T lymphocytes to destroy tumor cells. Pembrolizumab (KEYTRUDA®) is an anti-PD-1 (search) therapy that enhances the ability of the body’s immune system to detect and fight tumor cells. While the combination showed promise in preclinical studies, the KeyVibe-008 trial indicates that further research is needed to optimize its use in ES-SCLC.
Other Ongoing Trials
Merck (search) has several ongoing Phase 3 studies evaluating the vibostolimab and pembrolizumab fixed-dose combination in lung cancer, including KeyVibe-003, KeyVibe-006, and KeyVibe-007. These trials are routinely monitored by external data monitoring committees, and interim safety reviews have not resulted in any study modifications to date. The studies are undergoing ongoing comprehensive safety monitoring.