Domvanalimab has failed its pivotal phase 3 trial in untreated metastatic non-small cell lung cancer, and Gilead Sciences is stepping back from its collaboration with Arcus Biosciences.
The Star-221 study, launched in October 2022, was testing domvanalimab paired with Arcus’ anti-PD-1 antibody zimberelimab plus chemotherapy against Keytruda. Arcus disclosed the futility call in an April 20 SEC filing. No new safety signals emerged. A companion phase 2 NSCLC study was also cancelled.
Gilead is surrendering its option to license early-stage Arcus programs targeting CCR6, CD89, and CD40L. It’s keeping options on two clinical-stage candidates: the AXL inhibitor AB801 and the anti-CD39 antibody AB102, plus two preclinical assets including an MRGPRX2 antagonist and an unnamed TNF small molecule inhibitor.
The TIGIT field has been brutal. Roche, GSK, and BeOne Medicines all retreated after their own failures. Domvanalimab’s Fc-silent design was supposed to set it apart: its Fc function was deliberately mutated out, unlike most of the Fc-enabled antibodies that came before it. The data didn’t cooperate.
This defeat follows a head-to-head loss against BMS’s Opdivo in gastric and esophageal cancers, after brief promise in the Edge-Gastric study in October 2025. Arcus had already pivoted toward casdatifan, its HIF-2a inhibitor, and small-molecule inflammatory and autoimmune programs.
AstraZeneca’s rilvegostomig, a TIGIT/PD-1 bispecific, is the last candidate standing in the modality. Star-221 was scheduled to run through June 2028. It won’t.
Sarah Chen