A Safety and Efficacy Study of Treatment Combinations With and Without Chemotherapy in Adult Participants With Advanced Upper Gastrointestinal Tract Malignancies
EDGE-Gastric
A Phase 2 Trial to Evaluate the Safety and Efficacy of Combination Therapies in Patients With Advanced Upper Gastrointestinal Tract Malignancies (EDGE-Gastric)
3 other identifiers
interventional
332
6 countries
42
Brief Summary
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).
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_2
Started Jun 2022
Longer than P75 for phase_2
42 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
April 8, 2022
CompletedFirst Posted
Study publicly available on registry
April 15, 2022
CompletedStudy Start
First participant enrolled
June 10, 2022
CompletedPrimary Completion
Last participant's last visit for primary outcome
January 1, 2027
ExpectedStudy Completion
Last participant's last visit for all outcomes
June 1, 2027
April 29, 2026
April 1, 2026
4.6 years
April 8, 2022
April 28, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (2)
Number of Participants with Adverse Events (AEs)
Up to 18 months
Objective Response Rate (ORR) as measured by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
Up to 18 months
Secondary Outcomes (10)
Objective Response Rate (ORR) as measured by PD-L1 Expression Level
Up to 18 months
Overall survival (OS)
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
Up to 18 months
Disease Control (complete response, partial response, or stable disease) for greater than equal to 12 weeks
Up to 18 months
Duration of response (DOR) as determined by the Investigator according to RECIST v1.1
Up to 18 months
- +5 more secondary outcomes
Study Arms (7)
A1: First Line - Treatment Naïve Participants
EXPERIMENTALDomvanalimab and zimberelimab once every 4 weeks (Q4W) in addition to FOLFOX chemotherapy by intravenous (IV) infusion once every 2 weeks (Q2W)
A2: First Line - Treatment Naïve Participants
EXPERIMENTALZimberelimab Q4W in addition to chemotherapy with FOLFOX administered by IV infusion Q2W
A3 First Line - Treatment Naïve Participants
EXPERIMENTALNon-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
A4 First Line - Treatment Naïve Participants
EXPERIMENTALZimberelimab administered Q4W via IV infusion over 30 minutes, in addition to FOLFOX chemotherapy via IV infusion Q2W
B1: Second Line or greater Checkpoint Inhibitor Naïve Participants
EXPERIMENTALDomvanalimab and zimberelimab administered once every three weeks (Q3W) by IV infusion
B2: Second Line or greater Checkpoint Inhibitor Naïve Participants
EXPERIMENTALQuemliclustat Q2W and zimberelimab Q4W administered by IV infusion
Cohort C1: Second Line or greater - Checkpoint Inhibitor Experienced Participants
EXPERIMENTALDomvanalimab and zimberelimab Q3W administered by IV infusion
Interventions
Administered as specified in the treatment arm
Administered as specified in the treatment arm
Administered as specified in the treatment arm
Administered as specified in the treatment arm
Administered as specified in the treatment arm
Administered as specified in the treatment arm
Eligibility Criteria
You may qualify if:
- 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
You may not qualify if:
- 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.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Arcus Biosciences, Inc.lead
- Gilead Sciencescollaborator
Study Sites (42)
Research Site
Phoenix, Arizona, 85054, United States
Research Site
Los Angeles, California, 90033, United States
Research Site
Santa Monica, California, 90024, United States
Research Site
Derby, Connecticut, 06418, United States
Research Site
Fort Myers, Florida, 33901, United States
Research Site
Jacksonville, Florida, 32224, United States
Research Site
St. Petersburg, Florida, 33705, United States
Research Site
Boston, Massachusetts, 02109, United States
Research Site
New York, New York, 10021-0005, United States
Research Site
New York, New York, 10032, United States
Research Site
Durham, North Carolina, 27710, United States
Research Site
Columbus, Ohio, 43219, United States
Research Site
Oklahoma City, Oklahoma, 73104, United States
Research Site
Nashville, Tennessee, 37203, United States
Research Site
Nashville, Tennessee, 37232, United States
Research Site
Fairfax, Virginia, 22031, United States
Research Site
Toronto, Canada
Research Site
Las Condes, Chile
Research Site
Recoleta, Chile
Research Site
Santiago, Chile
Research Site
Talca, Chile
Research Site
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
Belgrade, Serbia
Research Site
Kamenitz, Serbia
Research Site
Kragujevac, Serbia
Research Site
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
Related Publications (1)
Janjigian YY, Oh DY, Pelster M, Wainberg ZA, Prusty S, Nelson S, DuPage A, Thompson A, Koralek DO, Sison EAR, Rha SY. Domvanalimab and zimberelimab in advanced gastric, gastroesophageal junction or esophageal cancer: a phase 2 trial. Nat Med. 2025 Dec;31(12):4274-4280. doi: 10.1038/s41591-025-04022-w. Epub 2025 Oct 18.
PMID: 41109921DERIVED
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- STUDY DIRECTOR
Medical Director
Arcus Biosciences, Inc.
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
April 8, 2022
First Posted
April 15, 2022
Study Start
June 10, 2022
Primary Completion (Estimated)
January 1, 2027
Study Completion (Estimated)
June 1, 2027
Last Updated
April 29, 2026
Record last verified: 2026-04
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, SAP, CSR
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.