Merck Stops Phase 3 TIGIT Trial Due to Immune-Mediated Adverse Events

Merck & Co. has decided to halt a phase 3 trial of its anti-TIGIT antibody, vibostolimab, due to a high rate of discontinuations, making the trial's success unlikely. The pharmaceutical giant was evaluating vibostolimab in combination with their anti-PD-1 immunotherapy, Keytruda, in the KeyVibe-010 trial. This trial aimed to assess the combination as an adjuvant treatment for patients with resected high-risk melanoma. However, the trial faced a significant setback when a higher rate of discontinuations occurred, primarily due to "immune-mediated adverse experiences" among patients receiving the combination therapy. Consequently, it became "highly unlikely that the trial could achieve a statistically significant improvement" in its primary endpoint of recurrence-free survival, as stated by the company.

Due to these developments, the independent data monitoring committee recommended that Merck unblind the trial and offer all patients the option to receive only Keytruda. Initially, the study was expected to provide results by 2026. Marjorie Green, senior vice president and head of oncology, global clinical development at Merck Research Laboratories, reiterated the company's commitment to exploring novel combinations and formulations that build on Keytruda, aiming to improve current standards of care for cancer patients.

This is not the first clinical challenge for vibostolimab. Last year, Merck disclosed that a combination of vibostolimab and Keytruda was less effective than the chemotherapy drug docetaxel in terms of progression-free survival among non-small cell lung cancer patients. Despite these setbacks, vibostolimab's journey is far from over. Merck is continuing with four other phase 3 lung cancer trials involving the antibody, collectively enrolling around 3,000 patients. The company emphasized that these trials would remain unaffected by the recent developments in the KeyVibe-010 trial.

In a December 2023 event, Merck's chief medical officer Eliav Barr, M.D., underscored the importance of phase 3 trials for TIGITs to prove their efficacy. He acknowledged that while some phase 2 studies had shown promise, phase 3 trials often presented more complexities. Barr indicated that the real value of the compound would become clear after evaluating the results of the phase 3 trials.

Merck's challenges with TIGITs are not unique. Other major pharmaceutical companies have also struggled to demonstrate the effectiveness of TIGIT blockade in cancer treatments, despite initial high expectations. However, there have been some positive developments in the field. For instance, Roche recently announced a phase 3 success for tiragolumab in treating esophageal cancer. Although the use of a comparator that is no longer the standard of care complicates the interpretation of the antibody's impact, it is still a positive step forward.

In summary, while Merck has faced significant hurdles with its vibostolimab trials, the company remains committed to investigating its potential in other ongoing phase 3 lung cancer trials. The broader pharmaceutical landscape also reflects the complexities and challenges of developing effective TIGIT inhibitors for cancer treatment.