Arcus, Gilead halt Phase III TIGIT lung cancer trial for futility; collaboration narrows

Arcus Biosciences has discontinued the Phase III STAR-121 trial of TIGIT-targeted domvanalimab in first-line metastatic non-small cell lung cancer (NSCLC) after a planned interim analysis found the study unlikely to meet its endpoint, as revealed in an SEC filing. Alongside that announcement, Arcus revealed that Gilead would not be exercising its option to the molecule, dealing a setback to their TIGIT program and broader partnership.

The decision followed a recommendation from an Independent Data Monitoring Committee based on a pre-specified futility analysis. STAR-121 evaluated the anti-TIGIT antibody domvanalimab in combination with the anti-PD-1 antibody zimberelimab and chemotherapy versus pembrolizumab plus chemotherapy in the first-line setting.

Safety was not formally assessed at the futility analysis, though no new safety issues had been identified in ongoing reviews. An exploratory arm evaluating zimberelimab plus chemotherapy showed overall survival consistent with pembrolizumab plus chemotherapy.

The discontinuation extends to the Phase II EDGE-Lung study, with Gilead Sciences working with investigators on next steps for enrolled patients.

Separately, the companies disclosed that Gilead will not exercise its option to extend collaboration rights under the 2020 agreement, allowing the option period to expire on July 14, 2026. As a result, Gilead will not gain rights to additional early-stage programs, including CCR6, CD89, and CD40L.

Gilead retains time-limited options on select assets, including AB801, AB598, AB102, and a TNF small molecule inhibitor. Arcus Biosciences also retains full rights to its HIF-2α inhibitor casdatifan outside previously licensed Asian territories.

The outcome adds to broader uncertainty around TIGIT-targeting strategies in lung cancer, where multiple late-stage programs have struggled to demonstrate benefit in combination with PD-1 blockade.