Merck Ends KeyVibe-008 Trial Over Safety Concerns: A Setback in Lung Cancer

Merck has discontinued its KeyVibe-008 trial for extensive-stage small cell lung cancer due to unmet primary endpoints and increased adverse events. The trial evaluated a fixed-dose combination of vibostolimab and pembrolizumab. Despite this setback, Merck remains committed to advancing lung cancer research, including ongoing trials and collaborations with Daiichi Sankyo on new therapeutic options.

Pharmaceutical giant Merck has announced the discontinuation of the KeyVibe-008 clinical trial, aimed at treating extensive-stage small cell lung cancer (ES-SCLC). This decision, influenced by the recommendations of an independent Data Monitoring Committee (DMC), marks a pause in what was anticipated to be a promising advance in cancer therapy.

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.

Dr. Marjorie Green, SVP and Head of Oncology at Merck Research Laboratories, expressed disappointment over the trial's outcome, stating, “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.”

The phase 3 trial was evaluating a novel fixed-dose combination of vibostolimab, an anti-TIGIT antibody, and pembrolizumab—Merck’s acclaimed anti-PD-1 therapy, KEYTRUDA®—in conjunction with chemotherapy. 

This regimen was compared against the established therapy of atezolizumab combined with chemotherapy. However, a pre-planned interim analysis revealed that the trial did not meet its primary endpoint of improving overall survival, prompting the DMC to declare the study futile.

Compounding the trial’s challenges, the Merck-led study noted a higher incidence of adverse events in patients receiving the new combination therapy compared to those on the control arm. These included both general and immune-related adverse events, raising concerns about patient safety and treatment efficacy.

Despite this setback, Merck's research efforts in lung cancer remain robust. The company highlighted ongoing trials, such as KeyVibe-003, KeyVibe-006, and KeyVibe-007, which continue to explore the therapeutic potential of vibostolimab and pembrolizumab in various settings.

Further, Merck is advancing its partnership with Daiichi Sankyo, exploring other promising agents like the investigational antibody-drug conjugate ifinatamab deruxtecan (I-DXd) in relapsed SCLC. This collaboration recently extended to include MK-6070, a delta-like ligand 3 (DLL3) targeting T-cell engager, showcasing an aggressive strategy to combat lung cancer at multiple stages.