News Releases

Taiho Pharmaceutical Co., Ltd. (“Taiho”) today announced the discontinuation of the Phase 3 STAR-221 study due to futility. STAR-221 study, conducted with Arcus Biosciences, Inc.(“Arcus”) and Gilead Sciences, Inc.(“Gilead”), evaluated the anti-TIGIT antibody domvanalimab (development code: AB154) plus anti-PD-1 antibody zimberelimab (development code: AB122) and chemotherapy versus nivolumab plus chemotherapy as first-line treatment for HER2-negative advanced gastric and esophageal cancers. The decision is based on the recommendation from the Independent Data Monitoring Committee (IDMC) following their review of data from an event-driven, pre-specified interim analysis of overall survival (OS), the primary endpoint of the study.

At the interim analysis, the combination of domvanalimab plus zimberelimab and chemotherapy did not improve OS relative to nivolumab plus chemotherapy, the standard of care. The safety profile for the combination of domvanalimab plus zimberelimab and chemotherapy was similar to that of nivolumab plus chemotherapy, and there were no new safety findings.

The companies are communicating with investigators to determine appropriate next steps for patients in the study. Detailed analysis to understand these results are being conducted.

Domvanalimab and zimberelimab are investigational molecules, and this combination therapy have not received approval from any regulatory authority for any use globally, and their safety and efficacy have not been established.

According to the World Health Organization, gastric cancer and esophageal cancer are the fifth and seventh leading causes of cancer deaths globally, accounting for more than 1.1 million cancer deaths each year. More than one-third of patients are diagnosed at an advanced stage, when five-year survival rates are only 5-7%. ^1,2

The STAR-221 study is a global, randomized, open-label, Phase 3 trial evaluating domvanalimab plus zimberelimab and chemotherapy versus nivolumab plus chemotherapy as a first-line treatment in locally advanced unresectable or metastatic HER2-negative gastric, gastroesophageal junction and esophageal adenocarcinomas. The study enrolled 1,040 patients from nearly 30 countries and participants were randomized 1:1 between two arms:

The primary endpoint of the study is overall survival. Key secondary endpoints include progression-free survival (PFS) and patient-reported outcomes (PROs). Secondary endpoints include objective response rate (ORR), duration of response (DOR) and safety.

Taiho Pharmaceutical has development and commercial rights in Japan and other countries in Asia, excluding China, for domvanalimab and zimberelimab, and is conducting the ongoing STAR-221 Phase 3 registrational study in Japan.

More information about STAR-221 is available at ClinicalTrials.gov: NCT05568095.

Domvanalimab is an Fc-silent investigational monoclonal antibody which binds the T-cell immunoreceptor with Ig and ITIM domains (TIGIT), a checkpoint receptor on immune cells that acts as a brake on the anticancer immune response. By binding to TIGIT with Fc-silent properties, domvanalimab is believed to work by freeing up immune-activating pathways and activating immune cells to attack and kill cancer cells without depleting the peripheral regulatory T cells important in avoiding immune-related toxicity.

Combined inhibition of both TIGIT and programmed cell death protein-1 (PD-1) is believed to enhance immune cell activation, as these checkpoint receptors play distinct, complementary roles in anti-tumor activity.

Zimberelimab is an anti-programmed cell death protein-1 (PD-1) monoclonal antibody that binds PD-1, with the goal of restoring the antitumor activity of T cells.

Zimberelimab is being evaluated in the U.S. and globally as a foundational anti-PD-1 treatment option in multiple ongoing clinical studies in combination with other immunotherapies.

Based on the option and license agreement that Taiho and Arcus entered into in 2017, Taiho has obtained exclusive development and commercialization rights to a total of five Arcus programs in Japan and certain other territories in Asia (excluding mainland China): (1) etrumadenant, a dual A2a/b adenosine receptor antagonist program in 2018; (2) zimberelimab, the anti-PD-1 program in 2019; (3) domvanalimab, the anti-TIGIT program in 2021; (4) quemliclustat, CD73 inhibitor program in 2024, and (5) casdatifan, HIF-2α inhibitor in 2025.

Arcus Biosciences is a clinical-stage, global biopharmaceutical company developing differentiated molecules and combination therapies for people with cancer, inflammatory and autoimmune diseases. In partnership with industry collaborators, patients and physicians around the world, Arcus is expediting the development of first- and/or best-in-class medicines against well-characterized biological targets and pathways and studying novel, biology-driven combinations that have the potential to help people with cancer live longer. Founded in 2015, the company has advanced multiple investigational medicines into registrational clinical trials including casdatifan, a HIF-2a inhibitor for clear cell renal cell carcinoma, and quemliclustat, a small-molecule CD73 inhibitor for pancreatic cancer. For more information about Arcus Biosciences’ clinical and preclinical programs, please visit www.arcusbio.com.

Gilead Sciences, Inc. is a biopharmaceutical company that has pursued and achieved breakthroughs in medicine for more than three decades, with the goal of creating a healthier world for all people. The company is committed to advancing innovative medicines to prevent and treat life-threatening diseases, including HIV, viral hepatitis, COVID-19, cancer, and inflammation. Gilead operates in more than 35 countries worldwide, with headquarters in Foster City, Calif.

1. https://gco.iarc.who.int/media/globocan/factsheets/cancers/6-oesophagus-fact-sheet.pdf (Last accessed: December 2025.)

2. https://gco.iarc.who.int/media/globocan/factsheets/cancers/7-stomach-fact-sheet.pdf (Last accessed: December 2025.)