‘Au Revoir TIGIT’: Gilead, Arcus Cut Gastro Cancer Drug After Late-Stage Failure

Arcus Biosciences and Gilead Sciences are discontinuing development of the anti‑TIGIT antibody domvanalimab in advanced gastric and esophageal cancers after the Phase 3 STAR-221 trial was deemed futile for overall survival.1 2 4 5

STAR-221 tested domvanalimab plus Arcus’ anti‑PD‑1 antibody zimberelimab and chemotherapy versus Bristol Myers Squibb’s Opdivo (nivolumab) plus chemotherapy as first‑line treatment in advanced gastric and esophageal cancers.1 2 3 4 6

An independent data monitoring committee recommended stopping STAR‑221 after an interim analysis showed the domvanalimab regimen did not improve overall survival compared with the Opdivo-based control arm, with similar benefit and no new safety signals.1 2 3 4 6

Based on the Phase 3 failure, Arcus and Gilead will also stop the related Phase 2 EDGE‑Gastric study of domvanalimab combinations in gastric cancer and halt further development of domvanalimab in upper GI cancers.1 2 5 8

The setback adds to a growing list of TIGIT-class failures across biopharma, following discontinued or unsuccessful programs from GSK, Merck, Roche, BeOne Medicines, Agenus and iTeos, undermining earlier optimism about TIGIT as a major next‑generation checkpoint target.1 2 3 7

In response, Arcus will refocus R&D investment on casdatifan, a wholly owned HIF‑2α inhibitor for kidney cancer, and on its early‑stage inflammation and immunology pipeline, positioning casdatifan as the company’s new primary growth driver.1 2 3 5

Analysts at Truist Securities reacted to the news with the line “Au Revoir TIGIT”, indicating they are writing off the broader domvanalimab program despite remaining studies in other gastrointestinal and lung cancers and expecting Arcus to further trim its pipeline.1

Domvanalimab is an Fc‑silent anti‑TIGIT antibody, differing from many earlier Fc‑enabled TIGIT candidates that have also failed; with domvanalimab’s setback, AstraZeneca’s rilvegostomig (a TIGIT/PD‑1 bispecific using an Fc‑silent anti‑TIGIT) is now one of the few notable TIGIT assets still in active development.2

Despite the discontinuations, Arcus states it is well capitalized and will continue development of other programs such as quemliclustat (CD73 inhibitor) in pancreatic cancer, with a Phase 3 trial fully enrolled and data expected later in the decade.2 3 5

TIGIT (T cell immunoreceptor with Ig and ITIM domain) is an immunosuppressive receptor often overexpressed in tumors; repeated clinical failures of TIGIT‑blocking antibodies are prompting industry‑wide reassessment of this immuno‑oncology strategy.1 3