Gilead Sciences and Arcus Biosciences’ domvanalimab, one of the last anti-TIGIT antibodies still standing, has failed another trial—leading Gilead to pull further away from their once wide-ranging collaboration.
The phase 3 Star-221 study was testing domvanalimab with Arcus’ experimental anti-PD-1 drug zimberelimab, plus chemotherapy, versus Keytruda in patients with untreated metastatic non-small cell lung cancer (NSCLC). The trial kicked off in October 2022 and was due to run through June 2028.
But Arcus revealed in an April 20 Securities and Exchange Commission filing that the study had been ended for futility after an interim analysis of the data to date. No new safety issues were identified, the biopharma noted.
A phase 2 study assessing domvanalimab and zimberelimab in patients with NSCLC has also been canned.
Along with the end of their TIGIT dream, Arcus disclosed that Gilead has further loosened the ties between the two companies. Gilead has surrendered its option to license a range of early-stage programs at Arcus focused on the targets like CCR6, CD89 and CD40L, according to the filing.
However, Gilead has retained the option to license a pair of Arcus’ clinical-stage candidates—namely the AXL inhibitor AB801 and the anti-CD39 monoclonal antibody AB102—as well as two preclinical assets in the form of the MRGPRX2 antagonist AB102 and an unnamed TNF small molecule inhibitor.
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The end of the road for their TIGIT plans won’t come as a huge surprise to anyone at Gilead or Arcus headquarters. While domvanalimab showed a glimmer of hope in certain gastric and esophageal cancers in the midstage Edge-Gastric study back in October 2025, the TIGIT drug has since failed in a head-to-head against Bristol Myers Squibb’s Opdivo in the same indication.
That failure already persuaded Arcus to refocus its efforts outside of TIGIT, specifically on its asset casdatifan, an HIF-2a inhibitor once backed by Gilead, as well as its earlier stage small-molecule inflammatory and autoimmune programs.
Domvanalimab was one of the last TIGIT candidates still standing after high-profile clinical failures saw the likes of Roche, GSK and BeOne Medicines retreat from a modality that was once hailed as the future of immuno-oncology.
Most of those discarded candidates were Fc-enabled, meaning the antibodies retain a fully functional Fc region to bind to Fc receptors found on the cell surface and contribute to the protective antitumor functions of the immune system. In contrast, domvanalimab is known as Fc-silent, meaning the Fc function has been mutated out.
The only other TIGIT candidate still in the running—AstraZeneca’s TIGIT/PD-1 bispecific antibody rilvegostomig—uses an Fc-silent anti-TIGIT antibody from Compugen.
