Merck halts phase 3 TIGIT trial after immune-mediated adverse events prompt discontinuations

Merck & Co. has bailed early on a phase 3 test of the anti-TIGIT antibody vibostolimab after a high rate of discontinuations rendered the trial's success unlikely. 

The Big Pharma had been evaluating vibostolimab in combination with anti-PD-1 immunotherapy Keytruda in the KeyVibe-010 trial as an adjuvant treatment for patients with resected high-risk melanoma.

But a higher rate of discontinuations mainly due to “immune-mediated adverse experiences” among patients taking the combination regimen meant it was “highly unlikely that the trial could achieve a statistically significant improvement” in the primary endpoint of recurrence-free survival, the company said.

As a result, the independent data monitoring committee recommended that Merck unblind the trial and offer all patients the option of receiving just Keytruda. The study had originally been expected to read out in 2026.

“Through our clinical development program, we continue to ask the tough questions in an effort to fully explore the potential of novel co-formulations and combinations that build on the foundation of Keytruda, with a goal to improve upon current standards of care and help even more patients with cancer,” Marjorie Green, senior vice president and head of oncology, global clinical development at Merck Research Laboratories, said in the May 13 release.

This is not the first time vibostolimab has run into problems in the clinic. Last year, Merck revealed that a combination of vibostolimab and Keytruda was numerically less effective than the chemotherapy docetaxel in terms of progression-free survival among non-small cell lung cancer patients.

It’s still not the end of the road for vibostolimab, however. Merck has four other phase 3 lung cancer trials involving the antibody ongoing with a combined total of about 3,000 patients enrolled. None of these trials are expected to be altered in the wake of today’s news, the company stressed.

Talking to investors at an event back in December 2023, Merck’s chief medical officer Eliav Barr, M.D., identified phase 3 as where TIGITs would need to prove their worth. “We have to acknowledge that there have been phase 2 studies that have looked good, and then there's been phase 3s that have been more complex. So, the way I see the compound is we would wait to see phase 3 and go from there,” Barr said at the time.

Merck’s executives can take some comfort from the fact that their Big Pharma peers have also struggled to demonstrate the effect of TIGIT blockade on cancer, despite the high hopes once heaped on the modality. Still, the year got off to a decent start with Roche posting a phase 3 win for tiragolumab in esophageal cancer, even if the use of a comparator that is no longer the standard of care complicates efforts to tease out the antibody's impact.