Recently, biotechnology company Arcus Biosciences and its partner Gilead announced the formal termination of the Phase III clinical trial STAR-221 , which combines PD-1, TIGIT, and chemotherapy as first-line treatment for gastric cancer , because the study showed no efficacy in the interim analysis .

STAR-221 is a global, randomized, open-label phase III clinical trial that enrolled approximately 1040 patients with locally advanced, unresectable, or metastatic HER-2-negative gastric cancer, gastroesophageal junction cancer, and esophageal adenocarcinoma. The study aimed to evaluate the efficacy and safety of Arcus' anti-TIGIT monoclonal antibody domvanalimab in combination with its PD-1 inhibitor zimberelimab and chemotherapy regimens (FOLFOX or CAPOX) as first-line treatment, compared to the standard therapy nivolumab (Opdivo) in combination with chemotherapy.

The primary endpoint of the study was to assess overall survival (OS) in tumors with high PD-L1 expression (TAP ≥ 5%), PD-L1-positive tumors (TAP ≥ 1%), and the intention-to-treat population (all PD-L1 levels) based on central PD-L1 assays using tumor region positivity (TAP) scores.

The results showed that, compared with the control group, the domvanalimab combination regimen failed to significantly prolong overall survival , and the trial did not meet its primary endpoint. Although the safety profiles of the two groups were similar and no new safety signals were identified, the fact that the efficacy was insufficient was enough for both companies to take decisive action to cut their losses.

demonstrated encouraging data in the Phase II EDGE-Gastric study . Results released in October 2025 showed a median overall survival of 26.7 months, an objective response rate of 59%, and a median progression-free survival of 12.9 months in 41 patients. These data were considered proof of concept for STAR-221 at the time, providing strong support for initiating a large-scale Phase III trial.

The failure of STAR-221 prompted Arcus to quickly restructure its strategy. The company announced the immediate cessation of all development work with domvanalimab in the upper gastrointestinal oncology field , including the simultaneous termination of the ongoing Phase II EDGE-Gastric study. Instead, Arcus focused its resources on casdatifan (AB521), a potentially best-in-class HIF-2α inhibitor, and five small molecule projects targeting inflammatory and autoimmune diseases.

In conclusion , the termination of STAR-221 once again demonstrates that the path of tumor immunotherapy is fraught with uncertainty. From the impressive data of the Phase II study to the unexpected failure of the Phase III trial, this case highlights the significant gap between early exploration and confirmatory research in clinical trials.

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