Merck (NYSE: MRK), known as MSD outside of the United States and Canada,  announced the discontinuation of the Phase 3 KeyVibe-008 trial based on the recommendation of an independent Data Monitoring Committee (DMC). The trial is evaluating the investigational fixed-dose combination (coformulation) of vibostolimab, an anti-TIGIT antibody, and pembrolizumab (KEYTRUDA ^® ), Merck’s anti-PD-1 therapy, in combination with chemotherapy compared to atezolizumab in combination with chemotherapy, for the first-line treatment of patients with extensive-stage small cell lung cancer (ES-SCLC). At a pre-planned analysis, data showed that the primary endpoint of overall survival (OS) met the pre-specified futility criteria. Additionally, when compared to patients in the control arm, patients in the vibostolimab and pembrolizumab fixed-dose combination arm experienced a higher rate of adverse events (AEs) and immune-related AEs. A comprehensive analysis of this study is ongoing.

Merck is notifying study investigators of the decision and that patients should stop ongoing treatment with the fixed-dose combination of vibostolimab and pembrolizumab and be offered the option to be treated with atezolizumab. Results will be shared with the scientific community.

“Small cell lung cancer remains a difficult disease to treat, as evident by the seven percent five-year survival rate and limited advancements in treatment options,” said Dr. Marjorie Green, senior vice president and head of oncology, global clinical development, Merck Research Laboratories. “Innovative research plays a critical role in improving our understanding to help patients achieve better outcomes, and while we hoped the results would be different, we remain committed to investigating novel approaches to treat this debilitating disease. We are extremely grateful to all of the patients, caregivers and investigators for their participation in this study.”

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.

In SCLC, Merck and Daiichi Sankyo recently announced that the first patient has been dosed in the IDeate-Lung02 Phase 3 trial evaluating the efficacy and safety of investigational ifinatamab deruxtecan (I-DXd) in patients with relapsed SCLC versus treatment of physician’s choice of chemotherapy. Merck and Daiichi Sankyo also expanded their existing global co-development and co-commercialization agreement for three investigational DXd antibody-drug conjugates to include Merck’s MK-6070, an investigational delta-like ligand 3 (DLL3) targeting T-cell engager that is currently being evaluated in a Phase 1/2 clinical trial (NCT04471727). The companies are planning to evaluate MK-6070 in combination with I-DXd in certain patients with SCLC, as well as other potential combinations. Merck obtained MK-6070 through its acquisition of Harpoon Therapeutics.

Ongoing Phase 3 studies evaluating the vibostolimab and pembrolizumab fixed-dose combination in lung cancer, which are routinely monitored by external data monitoring committees, include KeyVibe-003 , KeyVibe-006 and KeyVibe-007 . Interim external data monitoring committee safety reviews have not resulted in any study modifications to date and the studies are undergoing ongoing comprehensive safety monitoring.