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

Arcus Biosciences

Status and phase: Enrolling; Phase 2

Conditions: Gastrointestinal Tract Malignancies

Treatments: Drug: Quemliclustat; Drug: Zimberelimab; Drug: Leucovorin; Drug: Oxaliplatin; Drug: Fluorouracil; Drug: Domvanalimab

Study type: Interventional

Funder types: Industry

Identifiers

NCT05329766

ARC-21

2021-006291-16 (EudraCT Number)

Details and patient eligibility

About

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).

Enrollment: 360 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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360 participants in 7 patient groups

A1: First Line - Treatment Naïve Participants

Experimental group

Description:

Domvanalimab and zimberelimab once every 4 weeks (Q4W) in addition to FOLFOX chemotherapy by intravenous (IV) infusion once every 2 weeks (Q2W)

Treatment:

Drug: Domvanalimab

Drug: Fluorouracil

Drug: Oxaliplatin

Drug: Leucovorin

Drug: Zimberelimab

A2: First Line - Treatment Naïve Participants

Experimental group

Description:

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

Treatment:

Drug: Fluorouracil

Drug: Oxaliplatin

Drug: Leucovorin

Drug: Zimberelimab

A3 First Line - Treatment Naïve Participants

Experimental group

Description:

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

Treatment:

Drug: Domvanalimab

Drug: Fluorouracil

Drug: Oxaliplatin

Drug: Leucovorin

Drug: Zimberelimab

A4 First Line - Treatment Naïve Participants

Experimental group

Description:

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

Treatment:

Drug: Fluorouracil

Drug: Oxaliplatin

Drug: Leucovorin

Drug: Zimberelimab

B1: Second Line or greater Checkpoint Inhibitor Naïve Participants

Experimental group

Description:

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

Treatment:

Drug: Domvanalimab

Drug: Zimberelimab

B2: Second Line or greater Checkpoint Inhibitor Naïve Participants

Experimental group

Description:

Quemliclustat Q2W and zimberelimab Q4W administered by IV infusion

Treatment:

Drug: Zimberelimab

Drug: Quemliclustat

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

Experimental group

Description:

Domvanalimab and zimberelimab Q3W administered by IV infusion

Treatment:

Drug: Domvanalimab

Drug: Zimberelimab