Setback For Arcus-Gilead Partnership: 221 Study Fails To Show Survival Benefit In Advanced Cancers

Arcus Biosciences, Inc. (RCUS) and its partner Gilead Sciences, Inc. (GILD) have decided to terminate the Phase 3 STAR-221 trial, marking a significant disappointment for the collaborative effort in oncology. The halt was triggered by interim data suggesting the experimental regimen lacks meaningful efficacy against chemotherapy alternatives.

Trial Collapse and Key Findings

The 221 study compared a combination therapy—featuring the anti-TIGIT antibody domvanalimab paired with the anti-PD-1 agent zimberelimab alongside chemotherapy—against nivolumab combined with chemotherapy for newly diagnosed advanced gastric and esophageal cancers. Following an Independent Data Monitoring Committee evaluation of survival metrics at a pre-planned checkpoint, results demonstrated that the domvanalimab-based approach failed to extend overall survival compared to the nivolumab control arm. While the tolerability data showed comparable safety profiles between the two regimens, the lack of OS advantage rendered the 221 program untenable.

Strategic Pivot and Pipeline Refocus

Rather than prolonging the development of domvanalimab in this indication, Arcus is redirecting resources toward casdatifan, a potential differentiated HIF-2α inhibitor displaying encouraging monotherapy activity. The company anticipates multiple casdatifan readouts throughout 2026, positioning it as a cornerstone asset. Rights to the molecule extend globally except Japan and select Asian markets, where Taiho Pharmaceutical secured an option in October 2025.

Expanded I&I Portfolio and Cash Position

The company is concurrently broadening its early-stage efforts across five programs targeting inflammatory and autoimmune conditions. A novel MRGPRX2 antagonist is projected to enter human testing in 2026. With approximately $1 billion in cash and marketable securities on hand, Arcus projects sufficient runway to sustain operations into the latter half of 2028, providing a buffer for its recalibrated development agenda.