Arcus Biosciences Pivots Research Focus After STAR-221 Failure, Eyes Growth Through Next-Gen Pipeline

Arcus Biosciences, Inc. (RCUS) has decided to halt its Phase 3 STAR-221 clinical trial conducted jointly with Gilead Sciences, Inc. (GILD) following disappointing efficacy results in the treatment of advanced gastric and esophageal malignancies. The Independent Data Monitoring Committee recommended discontinuation after reviewing interim overall survival data, which showed the experimental domvanalimab-zimberelimab-chemotherapy regimen failed to demonstrate survival advantages over the standard-of-care nivolumab plus chemotherapy approach for first-line treatment.

Clinical Trial Outcome and Strategic Implications

The STAR-221 investigation examined an anti-TIGIT antibody (domvanalimab) paired with an anti-PD-1 agent (zimberelimab) alongside chemotherapy. Despite the combination’s tolerable safety profile—comparable to the nivolumab control arm—it did not meet the primary endpoint of improved overall survival. This setback underscores the competitive challenges in immuno-oncology, where combination therapies face mounting difficulty demonstrating incremental benefits over established checkpoint inhibitors.

Refocusing Resources on HIF-2α Platform and Arcus Cloud Infrastructure

Rather than persisting with the failing program, Arcus is redirecting its development engine toward casdatifan, a HIF-2α inhibitor candidate demonstrating robust monotherapy activity. The company retained worldwide rights to casdatifan (excluding Japan and select Asian markets, which Taiho Pharmaceutical secured in October 2025), and anticipates multiple clinical readouts throughout 2026.

The organization is simultaneously expanding its early-stage portfolio targeting inflammatory and autoimmune conditions, with a small molecule MRGPRX2 modulator expected to enter human trials in 2026. These programs represent the foundation of Arcus’s diversification strategy.

Financial Position and Runway

With approximately $1 billion in cash reserves, Arcus maintains sufficient capital to fund operations through at least mid-2028, providing a multi-year runway for its evolving pipeline. This financial cushion enables the company to absorb the STAR-221 discontinuation while continuing investment in promising candidates without immediate pressure for major pivots or partnerships.

The STAR-221 discontinuation highlights how emerging biotech companies must rapidly adapt when clinical data diverge from expectations, redirecting focus toward programs with stronger probability-of-success profiles.