A Safety and Efficacy Study of Treatment Combinations With and Without Chemotherapy in Adult Participants With Advanced Upper Gastrointestinal Tract Malignancies (EDGE-Gastric)

August 28, 2026 updated by: Arcus Biosciences, Inc.

A Phase 2 Trial to Evaluate the Safety and Efficacy of Combination Therapies in Patients With Advanced Upper Gastrointestinal Tract Malignancies (EDGE-Gastric)

The purpose of this study is to evaluate the safety and preliminary clinical activity of treatment combinations with and without chemotherapy in participants with locally advanced unresectable or metastatic gastric, GEJ, and esophageal adenocarcinoma. Chemotherapy will consist of FOLFOX (oxaliplatin, leucovorin, fluorouracil).

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

332

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Canada
      • Toronto, Canada
        • Research Site
  • Chile
      • Las Condes, Chile
        • Research Site
      • Recoleta, Chile
        • Research Site
      • Santiago, Chile
        • Research Site
      • Talca, Chile
        • Research Site
  • France
      • Bordeaux, France
        • Research Site
      • Brest, France
        • Research Site
      • Caen, France
        • Research Site
      • Lille, France
        • Research Site
      • Lyon, France
        • Research Site
      • Marseille, France
        • Research Site
      • Montpellier, France
        • Research Site
      • Plérin, France
        • Research Site
      • Poitiers, France
        • Research Site
      • Rouen, France
        • Research Site
      • Toulouse, France
        • Research Site
      • Villejuif, France
        • Research Site
  • Serbia
      • Belgrade, Serbia
        • Research Site
      • Kamenitz, Serbia
        • Research Site
      • Kragujevac, Serbia
        • Research Site
  • South Korea
      • Busan, South Korea
        • Research Site
      • Daegu, South Korea
        • Research Site
      • Hwasun, South Korea
        • Research Site
      • Seongnam-si, South Korea
        • Research Site
      • Seoul, South Korea
        • Research Site
      • Suwon, South Korea
        • Research Site
  • United States
    • Arizona
      • Phoenix, Arizona, United States, 85054
        • Research Site
    • California
      • Los Angeles, California, United States, 90033
        • Research Site
      • Santa Monica, California, United States, 90024
        • Research Site
    • Connecticut
      • Derby, Connecticut, United States, 06418
        • Research Site
    • Florida
      • Fort Myers, Florida, United States, 33901
        • Research Site
      • Jacksonville, Florida, United States, 32224
        • Research Site
      • St. Petersburg, Florida, United States, 33705
        • Research Site
    • Massachusetts
      • Boston, Massachusetts, United States, 02109
        • Research Site
    • New York
      • New York, New York, United States, 10032
        • Research Site
      • New York, New York, United States, 10021-0005
        • Research Site
    • North Carolina
      • Durham, North Carolina, United States, 27710
        • Research Site
    • Ohio
      • Columbus, Ohio, United States, 43219
        • Research Site
    • Oklahoma
      • Oklahoma City, Oklahoma, United States, 73104
        • Research Site
    • Tennessee
      • Nashville, Tennessee, United States, 37203
        • Research Site
      • Nashville, Tennessee, United States, 37232
        • Research Site
    • Virginia
      • Fairfax, Virginia, United States, 22031
        • Research Site

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Key Inclusion Criteria:

  • Participants with histologically confirmed diagnosis of locally advanced unresectable or metastatic gastric, GEJ, or esophageal adenocarcinoma with life expectancy ≥3 months as assessed by the Investigator
  • Eastern cooperative oncology group (ECOG) Performance Score of 0-1
  • At least one measurable target lesion per RECIST v1.1.
  • Adequate organ and marrow function
  • Able to provide an archival tumor sample that is representative of the cancer under investigation and suitable for central PD-L1 testing

Key Exclusion Criteria:

  • Participants with underlying medical conditions that, in the Investigator's or Sponsor's opinion, will make the administration of investigational products hazardous
  • Only for Cohort A: Known Human Epidermal Growth Factor Receptor 2 (HER-2) positive tumor
  • Known untreated, symptomatic, or actively progressing central nervous system (brain) metastases. Participants with leptomeningeal metastases are excluded from enrollment.
  • Discontinued use of prior immune checkpoint therapy due to immune related adverse events; received prior treatment with an anti-TIGIT monoclonal antibody.
  • History of trauma or major surgery within 28 days prior to enrollment.

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: A1: First Line - Treatment Naïve Participants
Domvanalimab and zimberelimab once every 4 weeks (Q4W) in addition to FOLFOX chemotherapy by intravenous (IV) infusion once every 2 weeks (Q2W)
Drug: Oxaliplatin
Administered as specified in the treatment arm
Drug: Zimberelimab
Administered as specified in the treatment arm
Drug: Domvanalimab
Administered as specified in the treatment arm
Drug: Fluorouracil
Administered as specified in the treatment arm
Drug: Leucovorin
Administered as specified in the treatment arm
Experimental: A2: First Line - Treatment Naïve Participants
Zimberelimab Q4W in addition to chemotherapy with FOLFOX administered by IV infusion Q2W
Drug: Oxaliplatin
Administered as specified in the treatment arm
Drug: Zimberelimab
Administered as specified in the treatment arm
Drug: Fluorouracil
Administered as specified in the treatment arm
Drug: Leucovorin
Administered as specified in the treatment arm
Experimental: B1: Second Line or greater Checkpoint Inhibitor Naïve Participants
Domvanalimab and zimberelimab administered once every three weeks (Q3W) by IV infusion
Drug: Zimberelimab
Administered as specified in the treatment arm
Drug: Domvanalimab
Administered as specified in the treatment arm
Experimental: Cohort C1: Second Line or greater - Checkpoint Inhibitor Experienced Participants
Domvanalimab and zimberelimab Q3W administered by IV infusion
Drug: Zimberelimab
Administered as specified in the treatment arm
Drug: Domvanalimab
Administered as specified in the treatment arm
Experimental: B2: Second Line or greater Checkpoint Inhibitor Naïve Participants
Quemliclustat Q2W and zimberelimab Q4W administered by IV infusion
Drug: Zimberelimab
Administered as specified in the treatment arm
Drug: Quemliclustat
Administered as specified in the treatment arm
Experimental: A3 First Line - Treatment Naïve Participants

Non-randomized A3 safety run-in cohort: Domvanalimab and zimberelimab co-administered Q4W via IV infusion over 60 minutes in addition to FOLFOX chemotherapy via IV infusion Q2W.

After completion of A3 safety run-in cohort, participants are randomized to the A3 arm. Domvanalimab and zimberelimab co-administered Q4W via IV infusion over 30 minutes, in addition to FOLFOX chemotherapy via IV infusion Q2W
Drug: Oxaliplatin
Administered as specified in the treatment arm
Drug: Zimberelimab
Administered as specified in the treatment arm
Drug: Domvanalimab
Administered as specified in the treatment arm
Drug: Fluorouracil
Administered as specified in the treatment arm
Drug: Leucovorin
Administered as specified in the treatment arm
Experimental: A4 First Line - Treatment Naïve Participants
Zimberelimab administered Q4W via IV infusion over 30 minutes, in addition to FOLFOX chemotherapy via IV infusion Q2W
Drug: Oxaliplatin
Administered as specified in the treatment arm
Drug: Zimberelimab
Administered as specified in the treatment arm
Drug: Fluorouracil
Administered as specified in the treatment arm
Drug: Leucovorin
Administered as specified in the treatment arm

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Objective Response Rate (ORR) as measured by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
Time Frame: Up to 18 months
Up to 18 months
Number of Participants with Adverse Events (AEs)
Time Frame: Up to 18 months
Up to 18 months

Secondary Outcome Measures

Outcome Measure
Time Frame
Objective Response Rate (ORR) as measured by PD-L1 Expression Level
Time Frame: Up to 18 months
Up to 18 months
Overall survival (OS)
Time Frame: From date of first dose until the date of death due to any cause (approximately 18 months)
From date of first dose until the date of death due to any cause (approximately 18 months)
Progression-free survival (PFS) as determined by the Investigator according to RECIST v1.1
Time Frame: Up to 18 months
Up to 18 months
Disease Control (complete response, partial response, or stable disease) for greater than equal to 12 weeks
Time Frame: Up to 18 months
Up to 18 months
Duration of response (DOR) as determined by the Investigator according to RECIST v1.1
Time Frame: Up to 18 months
Up to 18 months
Plasma concentration of domvanalimab
Time Frame: Up to 18 months
Up to 18 months
Plasma concentration of zimberelimab
Time Frame: Up to 18 months
Up to 18 months
Plasma concentration of quemliclustat
Time Frame: Up to 18 months
Up to 18 months
Percentage of participants with anti-drug antibodies to domvanalimab
Time Frame: Up to 18 months
Up to 18 months
Percentage of participants with anti-drug antibodies to zimberelimab
Time Frame: Up to 18 months
Up to 18 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Arcus Biosciences, Inc.

Collaborators

Gilead Sciences

Investigators

  • Study Director: Medical Director, Arcus Biosciences, Inc.

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

June 10, 2022

Primary Completion (Estimated)

January 1, 2027

Study Completion (Estimated)

June 1, 2027

Study Registration Dates

First Submitted

April 8, 2022

First Submitted That Met QC Criteria

April 8, 2022

First Posted (Actual)

April 15, 2022

Study Record Updates

Last Update Posted (Actual)

August 31, 2026

Last Update Submitted That Met QC Criteria

August 28, 2026

Last Verified

April 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ARC-21
  • 2021-006291-16 (EudraCT Number)
  • 2024-511917-40-00 (Ctis)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

Arcus will provide access to individual de-identified participant data and related study documents (e.g., protocol, Statistical Analysis Plan [SAP], Clinical Study Report [CSR]) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions.

For more information, please visit our website.

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP
  • CSR

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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