Arcus Biosciences Completes Enrollment for Phase 3 Trial of Domvanalimab Regimen in Metastatic Upper GI Cancers

Arcus Biosciences, Inc., a clinical-stage biopharmaceutical company specializing in cancer therapies, has announced the completion of patient enrollment for its Phase 3 trial, STAR-221. This trial, conducted in partnership with Gilead Sciences, is investigating a combination therapy for upper gastrointestinal adenocarcinomas, including gastric, gastroesophageal junction, and esophageal cancers. The regimen being evaluated combines the Fc-silent anti-TIGIT antibody domvanalimab with the anti-PD-1 monoclonal antibody zimberelimab and chemotherapy.

Dimitry S.A. Nuyten, M.D., Ph.D., the Chief Medical Officer of Arcus Biosciences, highlighted the significant interest from the global medical community in this trial, noting that domvanalimab is the first and only anti-TIGIT antibody to reach a Phase 3 trial for upper gastrointestinal adenocarcinomas. The company is now preparing for the trial's readout and is optimistic about the potential impact on patients suffering from these types of cancers.

Prior results from a Phase 2 study, EDGE-Gastric, were presented at the American Society of Clinical Oncology (ASCO) Annual Meeting. The study tested the same combination of domvanalimab, zimberelimab, and chemotherapy in a similar patient population. Data revealed a median progression-free survival (PFS) of 12.9 months, outperforming historical benchmarks for anti-PD-1 plus chemotherapy alone. Remarkably, nearly 60% of patients achieved PFS at 12 months, and the regimen showed sustained improvement across various efficacy measures, even in patients with low PD-L1 expression. No unexpected safety concerns were reported at the data cutoff point.

The STAR-221 trial has enrolled approximately 1,050 participants globally. The primary endpoints of the study include overall survival in PD-L1-high tumors and in the intent-to-treat population covering all PD-L1 levels. Secondary endpoints encompass progression-free survival, objective response rate, and duration of response. Participants were randomized into two treatment arms:
1. Domvanalimab (1600 mg intravenously every four weeks) plus zimberelimab (480 mg intravenously every four weeks) and FOLFOX (every two weeks) or domvanalimab (1200 mg) plus zimberelimab (360 mg every three weeks) and CAPOX (every three weeks).
2. Nivolumab (240 mg intravenously every two weeks) plus FOLFOX (every two weeks) or nivolumab (360 mg) plus CAPOX (every three weeks).

Domvanalimab is an investigational Fc-silent monoclonal antibody targeting TIGIT, a checkpoint receptor on immune cells that inhibits the anticancer immune response. By binding to TIGIT without depleting peripheral regulatory T cells, domvanalimab aims to activate immune cells to attack cancer cells. It is being evaluated in various combinations, including with zimberelimab, another investigational anti-PD-1 monoclonal antibody, and other cancer immunotherapies and adenosine receptor antagonists in multiple clinical trials.

Zimberelimab is intended to restore T cell antitumor activity by binding to PD-1. It has shown high affinity, selectivity, and potency in different tumor types and is being investigated as a foundational anti-PD-1 treatment in several clinical studies. Zimberelimab has obtained approval in China for treating recurrent or metastatic cervical cancer and relapsed or refractory classical Hodgkin’s lymphoma through Guangzhou Gloria Biosciences Co. Ltd., which holds commercialization rights in greater China. However, it is not yet approved for use in the U.S. or other regions outside of China.

Arcus Biosciences, founded in 2015, focuses on developing innovative therapies and combination treatments for cancer. Collaborating with industry partners, patients, and physicians globally, Arcus is driven to expedite the development of first- or best-in-class medicines that target specific biological pathways. The company has rapidly advanced several investigational medicines into clinical studies, including new approaches targeting TIGIT, PD-1, the adenosine axis, and other biological targets.