Roche's TIGIT drug fails Phase 3 lung cancer survival endpoint

Roche's TIGIT drug has encountered significant setbacks in its development, culminating in the failure to achieve success in a pivotal late-stage cancer trial. This year has been particularly challenging for the class of drugs targeting TIGIT, which was once heralded as a promising avenue in the field of immuno-oncology.

The Swiss pharmaceutical company's tiragolumab, when combined with Tecentriq, did not meet the overall survival endpoint in the final analysis of the Phase 3 SKYSCRAPER-01 study. This trial was conducted on patients with previously untreated PD-L1-high locally advanced unresectable or metastatic non-small cell lung cancer (NSCLC). According to a press release issued on Tuesday, the study had already missed its other primary endpoint of progression-free survival two years prior. Despite this setback, Roche had hoped that the overall survival data would provide more positive results.

In a rapid follow-up announcement, just ten minutes after the TIGIT trial failure, Roche revealed its acquisition of Poseida Therapeutics for $1 billion upfront. Poseida is known for its advancements in cell therapy, indicating Roche's strategic pivot following the disappointing outcomes with tiragolumab.

The year has not been favorable for tiragolumab. In July, the combined treatment involving tiragolumab, Tecentriq, and chemotherapy failed to meet both progression-free survival and overall survival endpoints in another Phase 3 trial. This trial involved patients with previously untreated locally advanced unresectable or metastatic nonsquamous NSCLC. As a result of this failure, Roche decided to halt two other studies involving tiragolumab in different NSCLC forms as part of a broader pipeline adjustment.

Nevertheless, tiragolumab did achieve one success earlier in the year. In January, the drug met both survival endpoints in the SKYSCRAPER-08 study involving Asian patients with specific forms of esophageal squamous cell carcinoma. However, this positive outcome was tempered by the fact that the trial's comparator arm, which tested chemotherapy and placebo, did not match up to the latest standard of care that includes checkpoint inhibitors, diminishing the impact of these results.

Elsewhere in the TIGIT drug space, there was a glimmer of hope in September. GSK and iTeos reported that their TIGIT-targeting drug, belrestotug, combined with Jemperli, improved overall response rates by more than 30 percentage points compared to Jemperli alone in a Phase 3 trial for patients with previously untreated PD-L1-high locally-advanced or metastatic NSCLC. This result provides some optimism for the potential of TIGIT-targeting therapies, albeit within a different combination and context.

On the other hand, Merck experienced a significant setback in May when it had to terminate a late-stage study of its anti-TIGIT drug, vibostolimab, for skin cancer. The trial faced a high number of patient dropouts due to immune-related side effects, highlighting the challenges and complexities associated with developing TIGIT-targeting therapies.

Overall, the series of disappointments this year for Roche's TIGIT drug underscores the unpredictable nature of drug development and the high stakes involved in the quest for new cancer treatments. The mixed results across different trials and combinations reflect the ongoing challenges in harnessing the potential of TIGIT inhibitors to deliver consistent and significant clinical benefits.