Arcus Biosciences Halts Advanced Cancer Trial as Anti-TIGIT Strategy Falls Short of Clinical Benchmarks

Arcus Biosciences, Inc. (RCUS) and partner Gilead Sciences, Inc. (GILD) have terminated the Phase 3 STAR-221 trial following a futility determination by its Independent Data Monitoring Committee. The decision reflects interim analysis findings showing that the experimental regimen failed to deliver superior overall survival compared to the established standard of care in advanced gastrointestinal malignancies.

Trial Design and Disappointing Results

The STAR-221 study was designed to evaluate domvanalimab, an anti-TIGIT monoclonal antibody, combined with zimberelimab (anti-PD-1) and chemotherapy as first-line therapy for advanced gastric and esophageal cancers. This three-drug combination was tested against nivolumab plus chemotherapy in an event-driven trial design. At the interim efficacy review, the domvanalimab-containing arm failed to demonstrate OS improvement relative to the nivolumab control group. Notably, both regimens demonstrated comparable tolerability profiles, meaning the futility stemmed from efficacy gaps rather than safety concerns.

Strategic Pivot: Redirecting Resources

Rather than continuing down the anti-TIGIT pathway in gastric cancer, Arcus is reallocating development resources toward casdatifan, a HIF-2α inhibitor candidate that has shown robust single-agent antitumor activity. The company retains exclusive global development rights outside Japan and select Asian markets, having licensed those territories to Taiho Pharmaceutical Co., Ltd. in October 2025. Multiple casdatifan readouts are anticipated throughout 2026.

Supporting Immunology and Early-Stage Pipeline

Beyond oncology, Arcus intends to accelerate five early-stage programs targeting inflammatory and autoimmune conditions. A novel MRGPRX2-targeted small molecule is projected to enter clinical development in 2026, representing the company’s broader therapeutic ambitions beyond cancer.

Financial Runway

With approximately $1 billion in cash and investments on hand, Arcus projects sufficient capital to sustain operational spending through at least mid-2028, providing a multi-year window to generate meaningful clinical and regulatory milestones across its portfolio.