A Clinical Trial of a New Combination Treatment, Domvanalimab and Zimberelimab, Plus Chemotherapy, for People With an Upper Gastrointestinal Tract Cancer That Cannot be Removed With Surgery That Has Spread to Other Parts of the Body

Study Overview
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Brief Summary
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This randomized Phase 3 open-label study will compare the efficacy of the T-cell immunoglobulin and immunoreceptor tyrosine-based inhibitory motif (ITIM) domain (TIGIT) monoclonal antibody domvanalimab, the anti programmed cell death protein 1 (PD-1) monoclonal antibody zimberelimab, and multiagent chemotherapy versus the anti PD-1 monoclonal antibody nivolumab and multiagent chemotherapy in the first-line treatment of participants with locally advanced unresectable or metastatic gastric, gastroesophageal junction (GEJ), and esophageal adenocarcinoma.

Official Title
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A Randomized, Open-Label, Multicenter Phase 3 Trial of Domvanalimab, Zimberelimab, and Chemotherapy Versus Nivolumab and Chemotherapy in Participants With Previously Untreated Locally Advanced Unresectable or Metastatic Gastric, Gastroesophageal Junction, and Esophageal Adenocarcinoma

Conditions
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Advanced Upper Gastrointestinal Tract Adenocarcinoma

Intervention / Treatment
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* Drug: Domvanalimab
* Drug: Zimberelimab
* Drug: Capecitabine
* Drug: Fluorouracil
* Drug: Leucovorin
* Drug: Oxaliplatin
* Drug: Nivolumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age >= 18 years at the time of signing the informed consent. Capable of giving signed informed consent which is in compliance with the requirements and restrictions listed in the informed consent form (ICF) and in protocol. Histologically confirmed diagnosis of locally advanced unresectable or metastatic gastric, GEJ, or esophageal adenocarcinoma. Eastern Cooperative Oncology Group (ECOG) Performance Score of 0-1. At least one measurable target lesion per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. Exclusion Criteria: Underlying medical or psychiatric conditions that, in the investigator's or sponsor's opinion, will make the administration of study-specified therapy hazardous, including but not limited to: Interstitial lung disease, including history of interstitial lung disease or non-infectious pneumonitis. Active viral, bacterial, or fungal infections requiring parenteral treatment within 14 days of randomization. Clinically significant cardiovascular disease, such as New York Heart Association Class II or greater cardiac disease or cerebrovascular accident within 3 months prior to randomization, unstable angina, or new onset angina within 3 months prior to randomization, myocardial infarction within 6 months prior to randomization, or unstable arrhythmia within 3 months prior to randomization. History of prior solid-organ transplantation, including allogenic bone marrow transplantation. Dementia, psychiatric, or substance abuse disorders that would interfere with satisfying the requirements of the trial. Known human epidermal growth factor receptor 2 (HER-2) positive tumor. Known untreated, symptomatic, or actively progressing central nervous system (CNS) (brain) metastases. Participants with leptomeningeal metastases are excluded from enrollment. Received prior systemic treatment for locally advanced unresectable or metastatic gastric, GEJ, or esophageal adenocarcinoma. Disease progression within 6 months of neoadjuvant or adjuvant chemotherapy. Other protocol defined Inclusion/Exclusion criteria may apply.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Domvanalimab + Zimberelimab + FOLFOX/CAPOX (PI Choice)<br>Participants in this arm will receive Domvanalimab and zimberelimab doses once every 4 weeks (Q4W) in addition to chemotherapy with FOLFOX (oxaliplatin, leucovorin, fluorouracil) once every 2 weeks (Q2W) or Domvanalimab and zimberelimab once every 3 weeks (Q3W) in addition to chemotherapy with CAPOX (capecitabine and oxaliplatin) Q3W. | Drug: Domvanalimab<br>* Intravenous (IV) Aqueous Solution<br>* Other names: AB154;Drug: Zimberelimab<br>* IV Aqueous Solution<br>* Other names: AB122;Drug: Capecitabine<br>* Oral Tablets<br>Drug: Fluorouracil<br>* IV Aqueous Solution<br>Drug: Leucovorin<br>* IV Aqueous Solution<br>Drug: Oxaliplatin<br>* IV Aqueous Solution<br>|
| Active Comparator: Nivolumab + FOLFOX/CAPOX (PI Choice)<br>Participants in this arm will receive Nivolumab Q2W and FOLFOX Q2W or Nivolumab Q3W + CAPOX Q3W. | Drug: Capecitabine<br>* Oral Tablets<br>Drug: Fluorouracil<br>* IV Aqueous Solution<br>Drug: Leucovorin<br>* IV Aqueous Solution<br>Drug: Oxaliplatin<br>* IV Aqueous Solution<br>Drug: Nivolumab<br>* IV Aqueous Solution<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival |  | From randomization until death from any cause (Approximately 15 months) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free survival (PFS) |  | Approximately 15 months | 
| Objective response rate (ORR) |  | Approximately 15 months | 
| Duration of response (DOR) |  | Approximately 15 months | 
| Incidence and severity of adverse events (AEs) and serious adverse events (SAEs) |  | Approximately 15 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Domvanalimab, Zimberelimab, Nivolumab, Advanced upper gastrointestinal tract adenocarcinoma, Gastroesophageal junction cancer, Esophageal adenocarcinoma, Gastric cancer, Gastric adenocarcinoma