Merck has announced the discontinuation of its Phase 3 KeyVibe-008 trial, which was investigating a fixed-dose combination of vibostolimab (an anti-TIGIT antibody) and pembrolizumab (Keytruda) in combination with chemotherapy for the first-line treatment of patients with extensive-stage small cell lung cancer (ES-SCLC).
The decision follows a recommendation from an independent Data Monitoring Committee (DMC) after a pre-planned interim analysis showed that the primary endpoint of overall survival (OS) met pre-specified futility criteria. This means that the trial was unlikely to demonstrate a statistically significant benefit in OS compared to the control arm, which was treated with atezolizumab plus chemotherapy.
Additionally, the analysis revealed a higher rate of adverse events (AEs) and immune-related AEs in patients receiving the vibostolimab and pembrolizumab combination compared to those in the control group. This raised concerns about the safety profile of the combination therapy, leading to the trial's early termination.
Merck has communicated this decision to study investigators and advised them to stop the ongoing treatment with the combination therapy. Patients currently enrolled in the study are being offered the option to switch to atezolizumab as an alternative treatment.
Despite the setback, Merck remains committed to advancing research in lung cancer. The company is conducting multiple ongoing Phase 3 studies involving the vibostolimab and pembrolizumab fixed-dose combination in different lung cancer settings. These trials, which include KeyVibe-003, KeyVibe-006, and KeyVibe-007, are undergoing regular safety monitoring by external data committees, and no modifications have been made based on interim reviews so far.
In addition to its efforts with vibostolimab and pembrolizumab, Merck has partnered with Daiichi Sankyo to develop new therapies for small cell lung cancer (SCLC). This includes the IDeate-Lung02 Phase 3 trial, which is evaluating the efficacy of ifinatamab deruxtecan (I-DXd) in patients with relapsed SCLC, and the potential combination of MK-6070, a DLL3-targeting T-cell engager, with I-DXd in certain patient populations.
Merck's research in lung cancer is extensive, encompassing nearly 200 clinical trials and involving over 36,000 patients worldwide. The company aims to become leader in lung cancer treatment by exploring new combinations and fixed-dose formulations, including those that involve their leading anti-PD-1 therapy, KEYTRUDA. While small cell lung cancer (SCLC) represents only about 15% of all lung cancers, it is particularly aggressive with poor survival rates, underscoring the critical need for effective new treatments.
Despite the discontinuation of the KeyVibe-008 trial, Merck’s broader research efforts continue, focusing on earlier disease stages and innovative combinations that may ultimately improve outcomes for patients with lung cancer.
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