The pharma said Thursday it is stopping a late-stage study of its blockbuster Keytruda plus the anti-TIGIT antibody vibostolimab and chemotherapy as a first-line treatment for extensive-stage small cell lung cancer, following a recommendation from an independent data monitoring committee.
Merck announced Thursday that it is ending a late-stage trial of its blockbuster Keytruda, anti-TIGIT antibody vibostolimab and chemotherapy in the first line treatment of extensive-stage small cell lung cancer, after a recommendation from an independent data monitoring committee.
The Phase III KeyVibe-008 trial compared the anti-TIGIT, Keytruda and chemo combination against Roche’s Tecentriq. However, extensive-stage small cell lung cancer (ES-SCLC) patients who were taking the combo encountered a higher rate of adverse events, including immune-related adverse events. In addition, data showed that the primary endpoint of overall survival (OS) met the pre-specified futility criteria.
Merck said a comprehensive analysis is ongoing and that the company is notifying study investigators of the trial halt. Patients should stop ongoing treatment with the combination and be offered the option of being treated with Tencentriq, according to the announcement. Merck said it will share the study results 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,” Marjorie Green, senior vice president and head of oncology global clinical development for Merck Research Laboratories, said in a statement. “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.”
This is not the only setback that Merck has run into for its anti-TIGIT combinations. Last year, Merck axed a Phase II study investigating the combo of Keytruda and vibostolimab which failed to reach statistical significance in progression-free survival in treating metastatic non-small cell lung cancer (NSCLC) patients with progressive disease after treatment with immunotherapy and chemotherapy.
In May 2024, Merck also pulled the plug on a Phase III trial of a Keytruda and vibostolimab combo in skin cancer after a high rate of dropouts due to immune-mediated adverse events, which would have made reaching statistical significance unlikely.
However, Merck is still working on its combination of vibostolimab and Keytruda, investigating the combination in three separate clinical trials to treat NSCLC. The company said the interim external data from the committee safety reviews have not resulted in any modifications and are undergoing “comprehensive safety monitoring.”
Other pharmas have also encountered challenges with anti-TIGIT antibodies. Last month, Roche stopped a Phase III study of its antibody tiragolumab after revealing that it would not improve survival in patients with NSCLC. Last week, Massachusetts-based biotech Agenus announced that Bristol Myers Squibb returned the rights to a bispecific antibody that binds to TIGIT after forging a potential billion-dollar deal in 2021.
