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

NCT ID: NCT05329766

Last Updated: 2025-12-31

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

PHASE2

Total Enrollment

332 participants

Study Classification

INTERVENTIONAL

Study Start Date

2022-06-10

Study Completion Date

2027-06-30

Brief Summary

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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).

Detailed Description

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Conditions

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Gastrointestinal Tract Malignancies

Keywords

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

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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)

Group Type EXPERIMENTAL

Domvanalimab

Intervention Type DRUG

Administered as specified in the treatment arm

Zimberelimab

Intervention Type DRUG

Administered as specified in the treatment arm

Fluorouracil

Intervention Type DRUG

Administered as specified in the treatment arm

Leucovorin

Intervention Type DRUG

Administered as specified in the treatment arm

Oxaliplatin

Intervention Type DRUG

Administered as specified in the treatment arm

A2: First Line - Treatment Naïve Participants

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

Group Type EXPERIMENTAL

Zimberelimab

Intervention Type DRUG

Administered as specified in the treatment arm

Fluorouracil

Intervention Type DRUG

Administered as specified in the treatment arm

Leucovorin

Intervention Type DRUG

Administered as specified in the treatment arm

Oxaliplatin

Intervention Type DRUG

Administered as specified in the treatment arm

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

Group Type EXPERIMENTAL

Domvanalimab

Intervention Type DRUG

Administered as specified in the treatment arm

Zimberelimab

Intervention Type DRUG

Administered as specified in the treatment arm

Fluorouracil

Intervention Type DRUG

Administered as specified in the treatment arm

Leucovorin

Intervention Type DRUG

Administered as specified in the treatment arm

Oxaliplatin

Intervention Type DRUG

Administered as specified in the treatment arm

A4 First Line - Treatment Naïve Participants

Zimberelimab administered Q4W via IV infusion over 30 minutes, in addition to FOLFOX chemotherapy via IV infusion Q2W

Group Type EXPERIMENTAL

Zimberelimab

Intervention Type DRUG

Administered as specified in the treatment arm

Fluorouracil

Intervention Type DRUG

Administered as specified in the treatment arm

Leucovorin

Intervention Type DRUG

Administered as specified in the treatment arm

Oxaliplatin

Intervention Type DRUG

Administered as specified in the treatment arm

B1: Second Line or greater Checkpoint Inhibitor Naïve Participants

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

Group Type EXPERIMENTAL

Domvanalimab

Intervention Type DRUG

Administered as specified in the treatment arm

Zimberelimab

Intervention Type DRUG

Administered as specified in the treatment arm

B2: Second Line or greater Checkpoint Inhibitor Naïve Participants

Quemliclustat Q2W and zimberelimab Q4W administered by IV infusion

Group Type EXPERIMENTAL

Quemliclustat

Intervention Type DRUG

Administered as specified in the treatment arm

Zimberelimab

Intervention Type DRUG

Administered as specified in the treatment arm

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

Domvanalimab and zimberelimab Q3W administered by IV infusion

Group Type EXPERIMENTAL

Domvanalimab

Intervention Type DRUG

Administered as specified in the treatment arm

Zimberelimab

Intervention Type DRUG

Administered as specified in the treatment arm

Interventions

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Domvanalimab

Administered as specified in the treatment arm

Intervention Type DRUG

Quemliclustat

Administered as specified in the treatment arm

Intervention Type DRUG

Zimberelimab

Administered as specified in the treatment arm

Intervention Type DRUG

Fluorouracil

Administered as specified in the treatment arm

Intervention Type DRUG

Leucovorin

Administered as specified in the treatment arm

Intervention Type DRUG

Oxaliplatin

Administered as specified in the treatment arm

Intervention Type DRUG

Eligibility Criteria

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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

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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Gilead Sciences

INDUSTRY

Sponsor Role collaborator

Arcus Biosciences, Inc.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Medical Director

Role: STUDY_DIRECTOR

Arcus Biosciences, Inc.

Locations

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Mayo Clinic - Arizona

Phoenix, Arizona, United States

Site Status

USC/Norris Comprehensive Cancer Center

Los Angeles, California, United States

Site Status

Ronald Reagan UCLA Medical Center

Santa Monica, California, United States

Site Status

Yale Cancer Center

Derby, Connecticut, United States

Site Status

Florida Cancer Specialist - South

Fort Myers, Florida, United States

Site Status

Mayo Clinic - Jacksonville

Jacksonville, Florida, United States

Site Status

Florida Cancer Specialist - North

St. Petersburg, Florida, United States

Site Status

Massachusetts General Hospital

Boston, Massachusetts, United States

Site Status

Memorial Sloan Kettering Cancer Center

New York, New York, United States

Site Status

Columbia University

New York, New York, United States

Site Status

Duke University

Durham, North Carolina, United States

Site Status

Zangmeister Cancer Center

Columbus, Ohio, United States

Site Status

OU - Stephenson Cancer Center

Oklahoma City, Oklahoma, United States

Site Status

SCRI Tennessee Oncology - Nashville

Nashville, Tennessee, United States

Site Status

Vanderbilt-Ingram Cancer Center

Nashville, Tennessee, United States

Site Status

Virginia Cancer Specialists

Fairfax, Virginia, United States

Site Status

UHN - Princess Margaret Cancer Centre

Toronto, , Canada

Site Status

Clínica San Carlos de Apoquindo

Las Condes, , Chile

Site Status

Bradford Hill Centro de Investigaciones Clinicas

Recoleta, , Chile

Site Status

Centro de Estudios Clínicos SAGA

Santiago, , Chile

Site Status

Clínica Universidad Católica del Maule

Talca, , Chile

Site Status

Institut Bergonié _ Bordeaux

Bordeaux, , France

Site Status

CHU de Brest_Brest

Brest, , France

Site Status

Centre Baclesse - CAEN

Caen, , France

Site Status

Centre Oscar Lambret _ LILLE

Lille, , France

Site Status

Centre Léon Bérard _ Lyon

Lyon, , France

Site Status

Hôpital Timone - Marseille

Marseille, , France

Site Status

Institut de Recherche en Cancerologie de Montpellier

Montpellier, , France

Site Status

Centre Armoricain de Radiothérapie, d'Imagerie Médicale et d'Oncologie

Plérin, , France

Site Status

Pôle Régional de Cancérologie - Service d'Oncologie Médicale - Poitiers

Poitiers, , France

Site Status

CHU de Toulouse_Oncopole

Toulouse, , France

Site Status

Gustave Roussy - Villejuif

Villejuif, , France

Site Status

MSB - Medicinski Sistem Beograd

Belgrade, , Serbia

Site Status

University Clinical Center of Serbia

Belgrade, , Serbia

Site Status

University Hospital Medical Center (KBC) Bezanijska Kosa

Belgrade, , Serbia

Site Status

Institute of Oncology of Vojvodina

Kamenitz, , Serbia

Site Status

Clinical Center Kragujevac

Kragujevac, , Serbia

Site Status

Dong-A University Hospital

Busan, , South Korea

Site Status

Kyungpook National University Chilgok Hospital

Daegu, , South Korea

Site Status

Chonnam National University Hwasun Hospital

Hwasun, , South Korea

Site Status

CHA Bundang Medical Center

Seongnam-si, , South Korea

Site Status

Asan Medical Center Hospital

Seoul, , South Korea

Site Status

Korea University Anam Hospital

Seoul, , South Korea

Site Status

Korea University Guro Hospital

Seoul, , South Korea

Site Status

Samsung Medical Center

Seoul, , South Korea

Site Status

Seoul National University Hospital

Seoul, , South Korea

Site Status

Severance Hospital Cancer Center

Seoul, , South Korea

Site Status

Ajou University Hospital

Suwon, , South Korea

Site Status

St. Vincent's Hospital, The Catholic University of Korea

Suwon, , South Korea

Site Status

Countries

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Argentina United States Canada Chile France Serbia South Korea

References

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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.

Reference Type DERIVED
PMID: 41109921 (View on PubMed)

Related Links

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Other Identifiers

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2021-006291-16

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

2024-511917-40-00

Identifier Type: CTIS

Identifier Source: secondary_id

ARC-21

Identifier Type: -

Identifier Source: org_study_id