Arcus Biosciences Pivots Strategy As STAR-221 Trial Hits Roadblock In Gastric Cancer Program

Arcus Biosciences and its partner Gilead Sciences have brought their Phase 3 STAR-221 investigation to an early halt following recommendations from the Independent Data Monitoring Committee. The trial, which had been assessing a combination therapy approach in advanced gastric and esophageal cancers, failed to demonstrate superior survival outcomes compared to established treatment standards.

Trial Outcome and Clinical Implications

The 221-designated study examined whether pairing the anti-TIGIT antibody domvanalimab with the checkpoint inhibitor zimberelimab alongside chemotherapy could outperform the current benchmark of nivolumab-based chemotherapy for first-line advanced disease. At its interim efficacy checkpoint, the experimental regimen did not translate into the hoped-for overall survival advantage. Tolerability considerations remained favorable, with the domvanalimab combination exhibiting a safety profile comparable to the control arm, suggesting the agents themselves were manageable but lacked the clinical benefit needed to justify continued development in this indication.

Strategic Reorientation and Future Pipeline

Rather than dwelling on the 221 setback, Arcus has signaled its intention to intensify efforts around casdatifan, an HIF-2 alpha inhibitor candidate showing promise as a potential best-in-class therapy. The company anticipates multiple clinical readouts for this program throughout 2026. Additionally, Arcus retains full development rights to casdatifan in most territories after Taiho Pharmaceutical secured exclusive options for Japanese and select Asian markets in late 2025.

The firm is also channeling resources into five early-stage programs targeting inflammatory and autoimmune conditions, with a small-molecule MRGPRX2 antagonist slated to enter human trials in 2026. These initiatives reflect a deliberate shift toward adjacent therapeutic areas.

Financial Position Supports Sustained Development

With approximately one billion dollars in liquid resources and investments on hand, Arcus maintains sufficient runway to fund its pipeline through at least the second half of 2028. This financial cushion provides the runway needed to advance multiple programs concurrently and weather setbacks like the 221 discontinuation without immediate pressure to raise capital or make drastic portfolio cuts.