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)

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: Recruiting
• Conditions: Gastrointestinal Tract Malignancies
• Intervention / Treatment: Drug: Oxaliplatin; Drug: Zimberelimab; Drug: Domvanalimab; Drug: Quemliclustat; Drug: Fluorouracil; Drug: Leucovorin

• Study Type: Interventional
• Enrollment (Estimated): 360
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Medical Director; Phone Number: +1-510-462-3330; Email: ClinicalTrials@arcusbio.com

Study Locations

• Canada
  • Toronto, Canada
    • Recruiting
    • UHN - Princess Margaret Cancer Centre
• France
  • Bordeaux, France
    • Recruiting
    • Institut Bergonie
  • Brest, France
    • Recruiting
    • CHU de Brest_Brest
  • Caen, France
    • Recruiting
    • Centre François Baclesse
  • Lille, France
    • Recruiting
    • Centre Oscar Lambret
  • Lyon, France
    • Recruiting
    • Centre Leon Berard
  • Marseille, France
    • Recruiting
    • Hôpital Timone
  • Montpellier, France
    • Recruiting
    • Institut de Recherche en Cancerologie de Montpellier
  • Plérin, France
    • Recruiting
    • Centre Armoricain de Radiothérapie, d'Imagerie Médicale et d'Oncologie
  • Poitiers, France
    • Recruiting
    • Pôle Régional de Cancérologie - Service d'Oncologie Médicale - Poitiers
  • Rouen, France
    • Recruiting
    • Centre Henri Becquerel
  • Rouen, France
    • Recruiting
    • Centre Henri Becquerel - Rouen
  • Toulouse, France
    • Recruiting
    • CHU de Toulouse_Oncopole
• Korea, Republic of
  • Busan, Korea, Republic of
    • Recruiting
    • Dong-A University Hospital
  • Daegu, Korea, Republic of
    • Recruiting
    • Kyungpook National University Chilgok Hospital
  • Hwasun, Korea, Republic of
    • Recruiting
    • Chonnam National University Hwasun Hospital
  • Junggu, Korea, Republic of
    • Recruiting
    • Chungnam National University Hospital
  • Seongnam, Korea, Republic of
    • Recruiting
    • CHA Bundang Medical Center
  • Seoul, Korea, Republic of
    • Recruiting
    • Seoul National University Hospital
  • Seoul, Korea, Republic of
    • Recruiting
    • Samsung Medical Center
  • Seoul, Korea, Republic of
    • Recruiting
    • Korea University Anam Hospital
  • Seoul, Korea, Republic of
    • Recruiting
    • Korea University Guro Hospital
  • Seoul, Korea, Republic of
    • Recruiting
    • Asan Medical Center Hospital
  • Seoul, Korea, Republic of
    • Recruiting
    • Severance Hospital Cancer Center
  • Seoul, Korea, Republic of
    • Recruiting
    • The Catholic University of Korea Seoul Saint Mary's Hospital
  • Suwon, Korea, Republic of
    • Recruiting
    • Ajou University Hospital
  • Suwon-si, Korea, Republic of
    • Recruiting
    • St. Vincent's Hospital, The Catholic University of Korea
• Serbia
  • Belgrad, Serbia
    • Recruiting
    • MSB - Medicinski Sistem Beograd
  • Belgrade, Serbia
    • Recruiting
    • University Hospital Medical Center (KBC) Bezanijska Kosa
  • Kragujevac, Serbia
    • Recruiting
    • Clinical Center Kragujevac
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85054
      • Recruiting
      • Mayo Clinic - Arizona
  • California
    • Los Angeles, California, United States, 90033
      • Recruiting
      • USC/Norris Comprehensive Cancer Center
    • Santa Monica, California, United States, 90024
      • Recruiting
      • Ronald Reagan UCLA Medical Center
  • Connecticut
    • Derby, Connecticut, United States, 06418
      • Recruiting
      • Yale Cancer Center
  • Florida
    • Fort Myers, Florida, United States, 33901
      • Recruiting
      • SCRI - Florida Cancer Specialists - North Region Research Office
    • Jacksonville, Florida, United States, 32224
      • Recruiting
      • Mayo Clinic - Jacksonville
    • Saint Petersburg, Florida, United States, 33705
      • Recruiting
      • SCRI - Florida Cancer Specialists - South Region Research Office
  • Massachusetts
    • Boston, Massachusetts, United States, 02109
      • Recruiting
      • Massachusetts General Hospital
  • New York
    • Buffalo, New York, United States, 14203
      • Recruiting
      • Roswell Park Comprehensive Cancer Center
    • New York, New York, United States, 10065
      • Recruiting
      • Memorial Sloan Kettering Cancer Center
    • New York, New York, United States, 10032
      • Recruiting
      • Columbia University
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Recruiting
      • Duke University
  • Ohio
    • Columbus, Ohio, United States, 43219
      • Recruiting
      • Zangmeister Cancer Center
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • Recruiting
      • OU - Stephenson Cancer Center
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Recruiting
      • University of Pennsylvania
  • South Carolina
    • Spartanburg, South Carolina, United States, 29307
      • Recruiting
      • Greenville Health System Cancer Institute (Prisma)
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Recruiting
      • Vanderbilt-Ingram Cancer Center
    • Nashville, Tennessee, United States, 37203
      • Recruiting
      • SCRI Tennessee Oncology - Nashville
  • Virginia
    • Fairfax, Virginia, United States, 22031
      • Recruiting
      • Virginia Cancer Specialists-Fairfax Office

Participation Criteria

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

How is the study designed?

Design Details

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

Number of Arms

7

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	Up to 18 months
Number of Participants with Adverse Events (AEs)	Up to 18 months

Secondary Outcome Measures

Outcome Measure	Time Frame
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
Plasma concentration of domvanalimab	Up to 18 months
Plasma concentration of zimberelimab	Up to 18 months
Plasma concentration of quemliclustat	Up to 18 months
Percentage of participants with anti-drug antibodies to domvanalimab	Up to 18 months
Percentage of participants with anti-drug antibodies to zimberelimab	Up to 18 months

Collaborators and Investigators

• Sponsor: Arcus Biosciences, Inc.
• Collaborators: Gilead Sciences
• Investigators: Study Director: Medical Director, Arcus Biosciences, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): June 10, 2022
• Primary Completion (Estimated): September 1, 2026
• 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): April 8, 2024
• Last Update Submitted That Met QC Criteria: April 5, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: Gastric cancer; Esophageal adenocarcinoma; Gastroesophageal junction cancer; Gastric adenocarcinoma; Anti-PD-1 antibody; Zimberelimab; Domvanalimab; Anti-CD73; anti-TIGIT antibody; Quemliclustat
• Additional Relevant MeSH Terms: Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Protective Agents; Antineoplastic Agents, Immunological; Micronutrients; Vitamins; Immune Checkpoint Inhibitors; Antidotes; Vitamin B Complex; Fluorouracil; Oxaliplatin; Leucovorin; Quemliclustat
• Other Study ID Numbers: ARC-21; 2021-006291-16 (EudraCT Number)

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