Arcus Biosciences, Inc. (RCUS) announced Friday it's pulling the plug on its Phase 3 STAR-221 study, conducted alongside Gilead Sciences, Inc. (GILD), after an Independent Data Monitoring Committee determined the trial was unlikely to succeed.
The verdict came during a pre-specified interim analysis of overall survival data. STAR-221 was testing a combination therapy featuring the anti-TIGIT antibody domvanalimab plus anti-PD-1 antibody zimberelimab and chemotherapy against nivolumab plus chemotherapy in patients with previously untreated advanced gastric and esophageal cancers.
The results? The domvanalimab-based combination simply didn't improve overall survival compared to the nivolumab regimen. On the safety front, at least, the experimental combo performed similarly to the comparison arm with no unexpected red flags emerging.
Both STAR-221 and the related Phase 2 EDGE-Gastric studies will be discontinued. Arcus and Gilead are working with investigators to determine next steps for enrolled patients while conducting a detailed post-mortem of the data.
Betting Big on Kidney Cancer
Rather than lick its wounds, Arcus is redirecting its research dollars toward casdatifan, what it believes could be a best-in-class HIF-2α inhibitor for treating clear cell renal cell carcinoma.
The enthusiasm isn't baseless. Casdatifan targets a well-validated biological pathway and has shown impressive single-agent activity in over 120 late-line ccRCC patients enrolled in the ARC-20 Phase 1/1b study. The data demonstrate improvements across all efficacy measures, including overall response rate and progression-free survival, versus the only approved HIF-2α inhibitor currently on the market.
Arcus retains global rights to casdatifan except in Japan and parts of Asia, which were optioned to Taiho Pharmaceutical in October 2025.
The company has laid out an aggressive roadmap for casdatifan through 2026:
Early 2026: Additional ARC-20 monotherapy analyses in late-line ccRCC, including updated progression-free survival data for the 100 mg once-daily dose selected for Phase 3 development.
Mid-2026: More mature ARC-20 combination data evaluating casdatifan plus cabozantinib in IO-experienced patients, aligned with the ongoing Phase 3 PEAK-1 study.
Second Half 2026: Initial ARC-20 data in earlier-line treatment settings and a go/no-go decision for the Phase 3 portion of eVOLVE-RCC02.
Late 2026: Potential launch of a Phase 3 registrational trial in early-line or first-line ccRCC.
The Rest of the Pipeline
Arcus isn't putting all its eggs in the kidney cancer basket. The company is also advancing quemliclustat, a small-molecule CD73 inhibitor being evaluated in the Phase 3 PRISM-1 trial for first-line metastatic pancreatic ductal adenocarcinoma. That trial completed enrollment earlier this year, with results expected in 2027. The study is testing quemliclustat combined with gemcitabine and nab-paclitaxel against the standard treatment regimen.
Immunology Ambitions
Beyond oncology, Arcus is building out an immunology and inflammation portfolio focused on oral small-molecule programs that could compete with today's injectable therapies.
Two candidates are expected to enter clinical trials on the following timeline:
- 2026: MRGPRX2 targeting atopic dermatitis and chronic spontaneous urticaria.
- Late 2026 to Early 2027: TNF inhibitor for rheumatoid arthritis, psoriasis, and inflammatory bowel disease, including ulcerative colitis.
Price Action: RCUS stock dropped 11.10% to $23.35 at publication on Friday.
