Otsuka Unit Taiho Halts Phase 3 STAR-121 Trial After Futility Analysis

Otsuka Holdings Co., Ltd., through its oncology subsidiary Taiho Pharmaceutical Co., Ltd., has discontinued the Phase 3 STAR-121 trial after an interim futility analysis indicated the study was unlikely to meet its primary endpoint of overall survival.

The global, randomized, open-label trial was conducted in collaboration with Arcus Biosciences, Inc. and Gilead Sciences, Inc., and evaluated the investigational combination of domvanalimab (AB154), an anti-TIGIT antibody, and zimberelimab (AB122), an anti–PD-1 antibody, in combination with chemotherapy as a first-line treatment for metastatic Non-Small Cell Lung Cancer. Comparator arms included pembrolizumab plus chemotherapy, as well as zimberelimab with chemotherapy.

The study enrolled patients without actionable genomic alterations, including EGFR and ALK mutations, and assessed overall survival both in patients with PD-L1 expression of at least 1% and in the overall population. However, following a pre-planned interim review, the Independent Data Monitoring Committee (IDMC) determined that the trial was unlikely to demonstrate a statistically significant survival benefit, leading to the recommendation to terminate the study.

While safety was not formally evaluated as part of the futility analysis, no new safety signals have been identified in ongoing reviews. Investigators are currently being notified to determine appropriate next steps for patients participating in the trial.

The discontinuation represents a setback for the dual checkpoint inhibition strategy targeting TIGIT and PD-1, which is designed to enhance anti-tumor immune responses through complementary mechanisms. Domvanalimab is engineered as an Fc-silent antibody to block TIGIT without depleting regulatory T cells, aiming to reduce immune-related toxicity, while zimberelimab targets PD-1 to restore T-cell activity against tumors. The combination has been under investigation as a potential next-generation immunotherapy approach in lung cancer.

NSCLC accounts for approximately 85% of all lung cancer cases globally, with lung cancer remaining the leading cause of cancer-related mortality worldwide. Despite advances in immunotherapy, there remains a need for improved first-line treatment options, particularly for patients without targetable mutations.

Both domvanalimab and zimberelimab remain investigational, with no regulatory approvals to date, and their safety and efficacy have not been established. The programs are part of a broader collaboration between Taiho and Arcus under a 2017 agreement, which grants Taiho development and commercialization rights across Japan and parts of Asia for multiple immuno-oncology candidates.

Reference

Update on the Phase 3 STAR-121 Study of Anti-TIGIT Antibody Domvanalimab and Anti-PD-1 Antibody Zimberelimab in Non-Small Cell Lung Cancer | 2026 | TAIHO PHARMA