The domvanalimab, an anti-TIGIT antibody from Gilead Sciences and Arcus Biosciences, is one of the most recent remaining anti-TIGIT antibodies. Still, it is failing another trial, further distancing Gilead from its previously broad partnership.
The phase 3 Star-221 trial was comparing domvanalimab with Arcus experimental anti-PD-1 drug zimberelimab with chemotherapy to 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 a 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.
The domvanalimab and zimberelimab phase 2 trial in patients with NSCLC is also cancelled.
Along with the end of their TIGIT dream, Arcus disclosed that Gilead has further loosened the ties between the two companies. As per the filing, Gilead has given up its right to license an assortment of early-stage programs at Arcus centered on the targets such as CCR6, CD89, and CD40L.
Nevertheless, Gilead has not yet given up the right to license two Arcus clinical-stage candidates, both of which are the AXL inhibitor AB801 and anti-CD39 monoclonal antibody AB102, and two preclinical assets, which are the MRGPRX2 antagonist AB102 and an unnamed TNF small molecule antagonist.
Their TIGIT plans will not end in a massive, unexpected fashion at Gilead or Arcus headquarters. Although domvanalimab produced some ray of hope in some gastric and esophageal cancers in the midstage Edge-Gastric study in October 2025, the TIGIT drug has since been defeated in a head-to-head phase against Bristol Myers Squibb 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 became one of the remaining TIGIT candidates following high-profile clinical failures by other contenders such as Roche, GSK, and BeOne Medicines that had stepped out of a modality that had been touted as the future of immuno-oncology.
The vast majority of these discarded candidates were Fc-enabled, i.e., the antibodies still have a fully functional Fc region that attaches to Fc receptors located on the cell surface and helps the immune system to perform its protective antitumor functions. Conversely, domvanalimab is Fc-silent, that is, the Fc activity has been silenced.
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.
Why the TIGIT Program Failed
The Phase 3 STAR-121 trial tested a TIGIT-targeting antibody alongside a PD-1 inhibitor and chemotherapy in lung cancer patients. However, the results failed to demonstrate a meaningful survival advantage compared to existing standard treatments, leading to termination for futility.
Gilead Steps Back From Arcus Partnership
Following the TIGIT failure, Gilead Sciences has begun scaling back its collaboration with Arcus Biosciences. The company has declined to continue certain licensing options tied to early-stage programs, signaling reduced confidence in the broader TIGIT pipeline.
Scientific Complexity Behind Immunotherapy Targets
Developing next-generation immunotherapies is inherently complex. Even when early-phase trials show encouraging signals, larger late-stage studies often reveal limitations in efficacy. Differences in tumor biology, immune response variability, and resistance mechanisms can all influence outcomes, making success difficult to replicate at scale.
Challenges in Combination Therapy Design
Modern oncology increasingly relies on combination therapies, but designing the right mix remains a challenge. Factors such as dosing, sequencing, and patient selection play critical roles in determining whether combinations outperform standard treatments. Small misalignments in these variables can significantly impact trial results.
Financial and Strategic Consequences
Late-stage trial failures can have immediate financial implications, including reduced valuations, partnership changes, and reprioritization of pipelines. Companies often reassess collaboration agreements, focusing only on programs with the highest probability of success while cutting exposure to higher-risk assets.
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