Roche stops pivotal TIGIT trial after Keytruda lands knockout blow at first attempt

Keytruda has beaten Roche’s TIGIT drug candidate at the first interim analysis of a phase 2/3 lung cancer trial, prompting the Swiss drugmaker to stop the study and consider changes to the broader program.

The data come from SKYSCRAPER-06, a study that randomized patients to receive either tiragolumab and Roche’s checkpoint inhibitor Tecentriq or Merck & Co.’s Keytruda and chemotherapy. The participants had previously untreated, locally advanced unresectable or metastatic non-squamous non-small cell lung cancer (NSCLC). 

Roche found the survival data favored the Keytruda regimen at the first interim analysis. The assessment of progression-free survival (PFS) generated a hazard ratio of 1.27. A hazard ratio above 1 indicates the control performed better than the investigational treatment. 

Another tiragolumab NSCLC trial, SKYSCRAPER-01, previously found the anti-TIGIT failed to improve PFS, but leaked overall survival data suggested it may be having a positive effect on overall survival (OS). Roche saw no such silver lining in SKYSCRAPER-06. The OS hazard ratio was 1.33 at the first interim analysis, indicating that patients are living longer on Keytruda than tiragolumab.

Roche responded by setting out plans to unblind and stop the study. The Swiss drugmaker is continuing to test the TIGIT prospect in other clinical trials but said it will “evaluate any relevant changes needed to the ongoing tiragolumab program” in light of the SKYSCRAPER-06 failure.

The company is studying tiragolumab in a broad clinical development program, which features multiple NSCLC studies as well as trials in other forms of lung, esophageal and liver cancers. Roche has reported the failure of a small cell lung cancer trial, plus the PFS miss in SKYSCRAPER-01. An esophageal trial met its primary endpoint, but the use of an outdated control therapy left doubts about clinical significance. 

If SKYSCRAPER-01 keeps trending in the same direction, Roche could rack up a phase 3 OS win in NSCLC in the future. But, even if that happens, the company may again face questions about the comparator. SKYSCRAPER-01 is comparing the effect of adding tiragolumab or placebo to Tecentriq. Having failed to beat Keytruda in SKYSCRAPER-06, a win against Tecentriq in the other study could come with an asterisk.

Shares in Roche opened down more than 2% in Switzerland.