A Phase 2 Trial to Evaluate the Safety and Efficacy of Combination Therapies in Patients With Advanced Upper Gastrointestinal Tract Malignancies (EDGE-Gastric)
Overview
- Phase
- Phase 2
- Intervention
- Domvanalimab
- Conditions
- Gastrointestinal Tract Malignancies
- Sponsor
- Arcus Biosciences, Inc.
- Enrollment
- 332
- Locations
- 99
- Primary Endpoint
- Number of Participants with Adverse Events (AEs)
- Status
- Active, Not Recruiting
- Last Updated
- 3 days ago
Overview
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).
Investigators
Eligibility Criteria
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.
- •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.
- •Note: Other protocol defined Inclusion/Exclusion criteria may apply.
Arms & Interventions
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)
Intervention: Domvanalimab
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)
Intervention: Zimberelimab
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)
Intervention: Fluorouracil
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)
Intervention: Leucovorin
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)
Intervention: Oxaliplatin
A2: First Line - Treatment Naïve Participants
Zimberelimab Q4W in addition to chemotherapy with FOLFOX administered by IV infusion Q2W
Intervention: Zimberelimab
A2: First Line - Treatment Naïve Participants
Zimberelimab Q4W in addition to chemotherapy with FOLFOX administered by IV infusion Q2W
Intervention: Fluorouracil
A2: First Line - Treatment Naïve Participants
Zimberelimab Q4W in addition to chemotherapy with FOLFOX administered by IV infusion Q2W
Intervention: Leucovorin
A2: First Line - Treatment Naïve Participants
Zimberelimab Q4W in addition to chemotherapy with FOLFOX administered by IV infusion Q2W
Intervention: Oxaliplatin
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
Intervention: Zimberelimab
A4 First Line - Treatment Naïve Participants
Zimberelimab administered Q4W via IV infusion over 30 minutes, in addition to FOLFOX chemotherapy via IV infusion Q2W
Intervention: Oxaliplatin
B1: Second Line or greater Checkpoint Inhibitor Naïve Participants
Domvanalimab and zimberelimab administered once every three weeks (Q3W) by IV infusion
Intervention: Zimberelimab
B2: Second Line or greater Checkpoint Inhibitor Naïve Participants
Quemliclustat Q2W and zimberelimab Q4W administered by IV infusion
Intervention: Zimberelimab
Cohort C1: Second Line or greater - Checkpoint Inhibitor Experienced Participants
Domvanalimab and zimberelimab Q3W administered by IV infusion
Intervention: Zimberelimab
B1: Second Line or greater Checkpoint Inhibitor Naïve Participants
Domvanalimab and zimberelimab administered once every three weeks (Q3W) by IV infusion
Intervention: Domvanalimab
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
Intervention: Domvanalimab
B2: Second Line or greater Checkpoint Inhibitor Naïve Participants
Quemliclustat Q2W and zimberelimab Q4W administered by IV infusion
Intervention: Quemliclustat
Cohort C1: Second Line or greater - Checkpoint Inhibitor Experienced Participants
Domvanalimab and zimberelimab Q3W administered by IV infusion
Intervention: Domvanalimab
A4 First Line - Treatment Naïve Participants
Zimberelimab administered Q4W via IV infusion over 30 minutes, in addition to FOLFOX chemotherapy via IV infusion Q2W
Intervention: Fluorouracil
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
Intervention: Fluorouracil
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
Intervention: Leucovorin
A4 First Line - Treatment Naïve Participants
Zimberelimab administered Q4W via IV infusion over 30 minutes, in addition to FOLFOX chemotherapy via IV infusion Q2W
Intervention: Zimberelimab
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
Intervention: Oxaliplatin
A4 First Line - Treatment Naïve Participants
Zimberelimab administered Q4W via IV infusion over 30 minutes, in addition to FOLFOX chemotherapy via IV infusion Q2W
Intervention: Leucovorin
Outcomes
Primary Outcomes
Number of Participants with Adverse Events (AEs)
Time Frame: Up to 18 months
Objective Response Rate (ORR) as measured by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
Time Frame: Up to 18 months
Secondary Outcomes
- 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))
- 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 zimberelimab(Up to 18 months)
- Plasma concentration of domvanalimab(Up to 18 months)
- Plasma concentration of quemliclustat(Up to 18 months)
- Percentage of participants with anti-drug antibodies to zimberelimab(Up to 18 months)
- Percentage of participants with anti-drug antibodies to domvanalimab(Up to 18 months)
- Progression-free survival (PFS) as determined by the Investigator according to RECIST v1.1(Up to 18 months)