Merck halts phase 3 lung cancer TIGIT trial for futility, notes immune side effects

Merck & Co.'s TIGIT program has encountered another significant setback. Following the termination of a phase 3 melanoma trial some months ago, the pharmaceutical giant has now halted a crucial lung cancer study due to issues with both efficacy and safety identified during an interim review.

The affected trial involved 460 patients diagnosed with extensive-stage small cell lung cancer (SCLC). Participants were randomly assigned to either a fixed-dose combination of Merck’s Keytruda and anti-TIGIT antibody vibostolimab or Roche’s checkpoint inhibitor Tecentriq. Each patient received their respective treatment as a first-line therapy in conjunction with chemotherapy.

Merck’s fixed-dose combination, known as MK-7684A, did not meet expectations. An interim analysis revealed that the primary endpoint of overall survival met the pre-specified criteria for futility. Additionally, the study linked MK-7684A to a higher incidence of adverse events, particularly immune-related effects. As a result, Merck has advised investigators to discontinue treatment with MK-7684A and offer patients the option to switch to Tecentriq. The company is still reviewing the data and plans to share the findings with the scientific community.

This development marks the second significant blow to Merck’s efforts targeting TIGIT within a few months. In May, Merck halted a phase 3 melanoma trial due to a high rate of discontinuations primarily caused by “immune-mediated adverse experiences.” Immune-related adverse events have now emerged as a recurring problem in two of Merck’s phase 3 TIGIT trials.

Despite these setbacks, Merck continues to explore the potential of vibostolimab in combination with Keytruda in three phase 3 trials for non-small cell lung cancer (NSCLC), with primary completion dates scheduled for 2026 and 2028. According to the company, interim safety reviews conducted by external data monitoring committees have not led to any modifications in these studies so far.

These ongoing trials provide an opportunity for vibostolimab to redeem itself. Moreover, Merck is actively pursuing other strategies to treat SCLC, a challenging tumor type where Keytruda has not yet established efficacy. Despite the failure of Roche’s rival TIGIT drug in this difficult cancer, Merck has persisted in testing vibostolimab for SCLC.

Additionally, Merck has other prospects in the SCLC market. The company's $4 billion investment in Daiichi Sankyo’s antibody-drug conjugates has yielded a promising candidate. Furthermore, Merck’s acquisition of Harpoon Therapeutics for $650 million added a T-cell engager to their arsenal. This week, Merck integrated these efforts by partnering the former Harpoon program with Daiichi.

In summary, while Merck’s TIGIT program has faced significant challenges, particularly with immune-related adverse effects in phase 3 trials for melanoma and lung cancer, the company remains committed to exploring the potential of vibostolimab and other therapeutic strategies for treating challenging cancers like SCLC and NSCLC.