Merck & Co.’s TIGIT program has suffered another setback. Months after shuttering a phase 3 melanoma trial, the Big Pharma has terminated a pivotal lung cancer study after an interim review revealed efficacy and safety problems.
The trial enrolled 460 people with extensive-stage small cell lung cancer (SCLC). Investigators randomized the participants to receive either a fixed-dose combination of Merck’s Keytruda and anti-TIGIT antibody vibostolimab or Roche’s checkpoint inhibitor Tecentriq. All participants received their assigned therapy, as a first-line treatment, during and after chemotherapy regimen.
Merck’s fixed-dose combination, code-named MK-7684A, failed to move the needle. A pre-planned look at the data showed the primary overall survival endpoint met the pre-specified futility criteria. The study also linked MK-7684A to a higher rate of adverse events, including immune-related effects.
Based on the findings, Merck is telling investigators that patients should stop treatment with MK-7684A and be offered the option to switch to Tecentriq. The drugmaker is still analyzing the data and plans to share the results with the scientific community.
The action is the second big blow to Merck’s work on TIGIT, a target that has underwhelmed across the industry, in a matter of months. The earlier blow arrived in May, when a higher rate of discontinuations, mainly due to “immune-mediated adverse experiences,” led Merck to stop a phase 3 trial in melanoma. Immune-related adverse events have now proven to be a problem in two of Merck’s phase 3 TIGIT trials.
Merck is continuing to evaluate vibostolimab with Keytruda in three phase 3 non-SCLC trials that have primary completion dates in 2026 and 2028. The company said “interim external data monitoring committee safety reviews have not resulted in any study modifications to date.”
Those studies give vibostolimab a shot at redemption, and Merck has also lined up other attempts to treat SCLC. The drugmaker is making a big play for the SCLC market, one of the few solid tumors shut off to Keytruda, and kept testing vibostolimab in the setting even after Roche’s rival TIGIT drug failed in the hard-to-treat cancer.
Merck has other shots on goal in SCLC. The drugmaker’s $4 billion bet on Daiichi Sankyo’s antibody-drug conjugates secured it one candidate. Buying Harpoon Therapeutics for $650 million gave Merck a T-cell engager to throw at the tumor type. The Big Pharma brought the two threads together this week by partnering the ex-Harpoon program with Daiichi.