Both vibostolimab and favezelimab have had disappointing runs leading up to their termination, sustaining several late-stage failures.
Merck announced on Monday that it will discontinue the development of two cancer assets, vibostolimab and favezelimab, following underwhelming Phase III data. The pharma was studying both candidates as combination treatments with the blockbuster therapy Keytruda (pembrolizumab).
Vibostolimab is a monoclonal antibody that works by blocking the TIGIT pathway, in turn restoring the immune system’s anticancer activity and boosting the activity of T lymphocytes.
According to the Monday announcement, Merck was running the Phase III KeyVibe-003 and KeyVibe-007 trials, testing a fixed-dose combo of vibostolimab with Keytruda in certain non-small cell lung cancer (NSCLC) populations.However, during a pre-planned analysis, an independent Data Monitoring Committee (DMC) determined that both studies met their respective criteria for futility for the primary endpoint of overall survival, and recommended that both trials be terminated.
Merck also reported an excess of immune-related adverse events in patients treated with vibostolimab plus Keytruda, though this finding is consistent with the known safety profile of dual checkpoint inhibitor therapies, according to the company.
“Considering the totality of the data from the Phase 3 KeyVibe studies, including the efficacy outcomes from KeyVibe-003 and KeyVibe-007, the company has decided to discontinue the Phase 3 KeyVibe-006 trial and other vibostolimab studies,” Merck’s news release stated.
Monday’s announcement ends a disappointing run for vibostolimab. In December 2023, Merck reported that vibostolimab plus Keytruda and docetaxel failed to significantly improve progression-free survival in NSCLC patients who had progressed after immunotherapy and chemotherapy, as compared with docetaxel alone.
In May 2023, the pharma was forced to pull the plug on the Phase III KeyVibe-010 study, which was likewise testing vibostolimab plus Keytruda in resected, high-risk melanoma. The decision was driven by a higher rate of patients dropping out of the combo treatment arm, driven by immune-mediated adverse events.
Because of the patient discontinuations, an independent DMC concluded that it would be “highly unlikely” for the trial to achieve a significant improvement in recurrence-free survival.
A few months later, in August, the pharma revealed that the Phase III KeyVibe-008 study likewise met the futility criteria for its primary efficacy endpoint of overall survival, pushing Merck to discontinue the trial. KeyVibe-008 was testing vibostolimab with Keytruda and chemotherapy in patients with extensive-stage small cell lung cancer.
Aside from vibostolimab, Merck on Monday announced that it would drop the clinical development of the anti-LAG-3 antibody favezelimab following a “thorough evaluation of data from the favezelimab clinical program.” Merck will cease enrollment into the KEYFORM-008 study, which was testing favezelimab with Keytruda in relapsed or refractory classical Hodgkin lymphoma patients.
In September favezelimab failed the KEYFORM-007 study, in which it did not significantly improve overall survival in metastatic colorectal patients when combined with Keytruda, as compared with the current standard of care.
