CClinicalTrials.gg
Active, not recruitingNCT05329766EDGE-GastricUpdated Sep 29, 2026

A Safety and Efficacy Study of Treatment Combinations With and Without Chemotherapy in Adult Participants With Advanced Upper Gastrointestinal Tract Malignancies

A Phase 2 interventional study of Domvanalimab and Quemliclustat in Gastrointestinal Tract Malignancies, sponsored by Arcus Biosciences, Inc.. Active, not recruiting at 43 sites in 6 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-09-29.

Sponsored by Arcus Biosciences, Inc. · Phase 2, Interventional, and Treatment

Phase
Phase 2
Study type
Interventional
Enrollment
332
Allocation
Randomized
Ages
18 Years and older
Sex
All
01

Study 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).

02

Conditions studied

  • Gastrointestinal Tract Malignancies

Keywords

  • Domvanalimab
  • Quemliclustat
  • Zimberelimab
  • Esophageal adenocarcinoma
  • Gastric adenocarcinoma
  • Gastric cancer
  • Gastroesophageal junction cancer
  • Anti-PD-1 antibody
  • Anti-CD73
  • anti-TIGIT antibody
03

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

Eligibility criteria

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.

04

Study design

Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
None (open label)
Enrollment
332 participants (actual)

Study arms

  • 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: Domvanalimab · Drug: Zimberelimab · Drug: Fluorouracil · Drug: Leucovorin · Drug: Oxaliplatin

  • Experimental
    A2: First Line - Treatment Naïve Participants

    Zimberelimab Q4W in addition to chemotherapy with FOLFOX administered by IV infusion Q2W

    Drug: Zimberelimab · Drug: Fluorouracil · Drug: Leucovorin · Drug: Oxaliplatin

  • 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: Domvanalimab · Drug: Zimberelimab · Drug: Fluorouracil · Drug: Leucovorin · Drug: Oxaliplatin

  • 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: Zimberelimab · Drug: Fluorouracil · Drug: Leucovorin · Drug: Oxaliplatin

  • Experimental
    B1: Second Line or greater Checkpoint Inhibitor Naïve Participants

    Domvanalimab and zimberelimab administered once every three weeks (Q3W) by IV infusion

    Drug: Domvanalimab · Drug: Zimberelimab

  • Experimental
    B2: Second Line or greater Checkpoint Inhibitor Naïve Participants

    Quemliclustat Q2W and zimberelimab Q4W administered by IV infusion

    Drug: Quemliclustat · Drug: Zimberelimab

  • Experimental
    Cohort C1: Second Line or greater - Checkpoint Inhibitor Experienced Participants

    Domvanalimab and zimberelimab Q3W administered by IV infusion

    Drug: Domvanalimab · Drug: Zimberelimab

Interventions

  • DrugDomvanalimab

    Administered as specified in the treatment arm

  • DrugQuemliclustat

    Administered as specified in the treatment arm

  • DrugZimberelimab

    Administered as specified in the treatment arm

  • DrugFluorouracil

    Administered as specified in the treatment arm

  • DrugLeucovorin

    Administered as specified in the treatment arm

  • DrugOxaliplatin

    Administered as specified in the treatment arm

05

What researchers measure

Primary outcomes

  1. Number of Participants with Adverse Events (AEs)

    Time frame: Up to 18 months

  2. Objective Response Rate (ORR) as measured by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1

    Time frame: Up to 18 months

Secondary outcomes

  1. Objective Response Rate (ORR) as measured by PD-L1 Expression Level

    Time frame: Up to 18 months

  2. Overall survival (OS)

    Time frame: From date of first dose until the date of death due to any cause (approximately 18 months)

  3. Progression-free survival (PFS) as determined by the Investigator according to RECIST v1.1

    Time frame: Up to 18 months

  4. Disease Control (complete response, partial response, or stable disease) for greater than equal to 12 weeks

    Time frame: Up to 18 months

  5. Duration of response (DOR) as determined by the Investigator according to RECIST v1.1

    Time frame: Up to 18 months

  6. Plasma concentration of domvanalimab

    Time frame: Up to 18 months

  7. Plasma concentration of zimberelimab

    Time frame: Up to 18 months

  8. Plasma concentration of quemliclustat

    Time frame: Up to 18 months

  9. Percentage of participants with anti-drug antibodies to domvanalimab

    Time frame: Up to 18 months

  10. Percentage of participants with anti-drug antibodies to zimberelimab

    Time frame: Up to 18 months

06

Study locations

43 sites
  • 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
    Portland, Oregon 97213, 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
07

References and documents

Publications

  • 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. PubMed 41109921 ↗

Individual participant data

Plan to share: Yes — 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.

Supporting information: Study protocol, Sap, Csr

08

Registry details

Key details

Study ID
NCT05329766
Lead sponsor
Arcus Biosciences, Inc.
Collaborators
Gilead Sciences
Responsible party
Sponsor
First posted
Apr 15, 2022
Start date
Jun 10, 2022
Primary completion
Jan 2027 (estimated)
Completion
Jun 2027 (estimated)
Last update
Sep 29, 2026

Study contacts

Medical Director
study director · Arcus Biosciences, Inc.

Oversight

Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

Not currently enrolling

This study is active, not recruiting, as verified in Apr 2026. You cannot join it, but the record below documents what was studied.

Follow this study

Get an email when the registry record changes — status, dates, results — or when someone posts here.

Sign in to follow

Discussion

Questions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.

Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.

Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.

Start the discussion