Merck’s Keytruda, Anti-TIGIT Combo Fails Phase II NSCLC Trial

Merck research laboratories_iStock, hapabapa

Pictured: Merck Research Laboratories building in California/iStock, hapabapa

A combination of Merck’s blockbuster anti-PD-1 drug Keytruda and its experimental anti-TIGIT antibody vibostolimab failed to meet endpoints in a Phase II study of metastatic non-small cell lung cancer patients with progressive disease after treatment with immunotherapy and chemotherapy, the pharma giant reported Thursday. 

The results showed the combo, when it included docetaxel, had a median progression-free survival (PFS) of 2.4 months against those only treated with docetaxel. Still, the endpoint did not hit statistical significance and earned a p-value of p=0.0910. Vibostolimab and Keytruda alone did not improve the median PFS against docetaxel alone, having a PFS of 2.7 months against 3.2 months and a p-value of p=0.9622. 

The secondary endpoints of the study included overall survival, overall response rate, and duration of response, with overall survival and time of response not reaching their statistical significance. Merck also noted four treatment-related deaths in the vibostolimab, Keytruda, and docetaxel arm and one in each of the vibostolimab, Keytruda, and docetaxel-only component.

“This study was designed to evaluate a co-formulation of vibostolimab and pembrolizumab in a population of patients who are heavily pre-treated and have progressed following treatment with standard-of-care therapies, often leaving them with limited treatment options and a poor prognosis. We will leverage our evolving understanding of novel combinations and co-formulations to help inform our comprehensive research program evaluating this co-formulation across a wide range of tumor types,” Scot Ebbinghaus, vice president of global clinical development at Merck Research Laboratories, said in a statement.

Merck on Thursday also reported poor results for a combination of Keytruda and AstraZeneca’s PARP inhibitor Lynparza, which will not be going forward after failing to meet its endpoints in a Phase III trial in patients with metastatic squamous NSCLC. The company detailed that after an independent Data Monitoring Committee looked at the interim analysis it will be halting the study based on the committee’s recommendation. The combination of Keytruda, Lynparza, and chemotherapy did not improve overall survival when put up against a placebo.

The other endpoint in the study, PFS, was also not statistically significant, but Merck emphasized that there was “numerical improvement” when up against the control arm. Merck found no new safety issues and is informing investigators of the recommendation to put the kibosh on the study. Merck plans to unveil the full details of the data at a later point.

“While there have been significant scientific advancements in lung cancer research in recent years, unmet needs remain for patients with advanced non-small cell lung cancer,” Marjorie Green, senior vice president and head of late-stage oncology, global clinical development at Merck Research Laboratories, said in a statement.

Nonetheless, Keytruda remains a significant moneymaker for Merck and earned another approval from the FDA in November 2023 for the treatment of biliary tract cancer. The green light marked the sixth indication for the drug in gastrointestinal cancers.

Tyler Patchen is a staff writer at BioSpace. You can reach him at tyler.patchen@biospace.com. Follow him on LinkedIn.

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