NCT07283848

Zimberelimab + Domvanalimab in Gastroesophageal Adenocarcinoma

A Single-Arm, Phase II Study of Perioperative Zimberelimab + Domvanalimab and Neoadjuvant Chemotherapy in Locally Advanced, Resectable, Gastroesophageal Adenocarcinoma

• Status: Withdrawn
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 0 (actual)
• Sponsor: Massachusetts General Hospital · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

The purpose of the study is to understand whether study drugs domvanalimab and zimberelimab are safe and effective in combination with standard chemotherapy for patients with operable cancer of the esophagus, stomach, or gastroesophageal junction (where the stomach meets the esophagus). All participants will receive the study treatment. Participants will receive chemotherapy and two immune therapies drugs (domvanalimab and zimberelimab) for up to 4 months before surgery. After surgery and at least a 4 week recovery, participants will receive domvanalimab and zimberelimab for up to 8 months. After completion of the study treatment, participants will be followed for up to 5 years per standard of care.

Detailed description

This is a single-center, phase II study evaluating the efficacy, activity and safety of domvanalimab and zimberelimab with standard chemotherapy (FLOT: fluorouracil (also called 5FU), oxaliplatin, leucovorin, docetaxel) in locally advanced, resectable, gastroesophageal adenocarcinomas. This study will enroll up to 28 participants with untreated, locally advanced, resectable adenocarcinoma of the stomach and gastroesophageal junction. Participants will receive up to 8 2-week cycles of domvanalimab , zimberelimab, and FLOT. If there is no evidence of progressive disease and participants remain good surgical candidates, they will undergo surgery 4-6 weeks after last dose of FLOT as per standard of care. Beginning 4-12 weeks after surgery, participants will receive domvanalimab + zimberelimab for up to 8 4-week cycles. Total treatment duration is approximately 12 months. Participants will remain on study unless they do not safely tolerate therapy, develop progressive disease, or withdraw consent. Participants will be followed for up to 5 years. The U.S. Food and Drug Administration (FDA) has not approved zimberelimab, domvanalimab, and FLOT in combination as a treatment for any disease. The FDA has not approved zimberelimab as a treatment for any disease. The FDA has not approved domvanalimab as a treatment for any disease. The FDA has approved FLOT (5-FU, oxaliplatin, leucovorin, and docetaxel) as approved chemotherapy drugs used to treat stomach and gastroesophageal cancers, as well as among many other cancers. Arcus Biosciences, Inc. (with Gilead Sciences) are providing study drugs zimberelimab and domvanalimab. Gateway for Cancer Research, a nonprofit organization, is providing funding for this study.

Conditions

• Adenocarcinoma Stomach
• Adenocarcinoma Gastroesophageal Junction

Interventions

Type	Name	Description
DRUG	Zimberelimab	480mg administered intravenously once every 4 weeks before surgery (up to 4 doses) and once every 4 weeks after surgery (up to 8 doses).
DRUG	Domvanalimab	1600mg administered by intravenous \[IV\] infusion over about 60 minutes once every 4 weeks before surgery (up to 4 doses), and once every 4 weeks after surgery (up to 8 doses).
DRUG	FLOT (Fluorouracil+Leucovorin+Oxaliplatin+Docetaxel)	Administered by IV every 2 weeks before surgery for up to 8 doses. FLOT is given using a continuous IV infusion over 24 hours. FLOT will be administered according to standard clinical practice. Participants will receive FLOT before surgery but not after surgery.

Timeline

• Start date: 2026-02-01
• Primary completion: 2026-12-01
• Completion: 2029-12-01
• First posted: 2025-12-16
• Last updated: 2025-12-26

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study