A Safety and Efficacy Study of Domvanalimab + Zimberelimab Combination Therapy in Participants With Advanced Upper Gastrointestinal Tract Malignancies

Sponsor

Arcus Biosciences, Inc. (Industry)

Overall Status

Recruiting

CT.gov ID

NCT05329766

Collaborator

(none)

120

Enrollment

Locations

Arms

23.6

Anticipated Duration (Months)

Patients Per Site

2.5

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This study will evaluate the safety and efficacy of the anti-T cell immunoglobulin and ITIM domain (TIGIT) monoclonal antibody domvanalimab, the anti-programmed cell death protein 1 (PD-1) monoclonal antibody zimberelimab, and multiagent chemotherapy in the first-line setting, and of domvanalimab and zimberelimab in the second-line or greater setting in participants with locally advanced unresectable or metastatic esophageal, gastroesophageal junction (GEJ), and gastric adenocarcinoma.

Condition or Disease	Intervention/Treatment	Phase
Gastrointestinal Tract Malignancies	Drug: Zimberelimab Drug: Domvanalimab Drug: Fluorouracil Drug: Leucovorin Drug: Oxaliplatin	Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

120 participants

Allocation:

Non-Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Phase 2 Trial to Evaluate the Safety and Efficacy of Domvanalimab (AB154) and Zimberelimab (AB122) -Based Treatment Combinations in Patients With Advanced Upper Gastrointestinal Tract Malignancies

Actual Study Start Date :

Jun 10, 2022

Anticipated Primary Completion Date :

Mar 28, 2024

Anticipated Study Completion Date :

May 28, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Cohort A: First Line - Treatment Naïve Participants Domvanalimab and zimberelimab in addition to FOLFOX chemotherapy by intravenous (IV) infusion	Drug: Zimberelimab Zimberelimab is an anti-PD-1 monoclonal antibody Drug: Domvanalimab Domvanalimab is an anti-TIGIT monoclonal antibody Drug: Fluorouracil FOLFOX Drug: Leucovorin FOLFOX Drug: Oxaliplatin FOLFOX
Experimental: Cohort B: Second Line or greater Checkpoint Inhibitor Naïve Participants Domvanalimab and zimberelimab will be administered by IV infusion	Drug: Zimberelimab Zimberelimab is an anti-PD-1 monoclonal antibody Drug: Domvanalimab Domvanalimab is an anti-TIGIT monoclonal antibody
Experimental: Cohort C: Second Line or greater - Checkpoint Inhibitor Experienced Participants Domvanalimab and zimberelimab will be administered by IV infusion	Drug: Zimberelimab Zimberelimab is an anti-PD-1 monoclonal antibody Drug: Domvanalimab Domvanalimab is an anti-TIGIT monoclonal antibody

Arm

Intervention/Treatment

Experimental: Cohort A: First Line - Treatment Naïve Participants

Domvanalimab and zimberelimab in addition to FOLFOX chemotherapy by intravenous (IV) infusion

Drug: Zimberelimab

Zimberelimab is an anti-PD-1 monoclonal antibody

Drug: Domvanalimab

Domvanalimab is an anti-TIGIT monoclonal antibody

Drug: Fluorouracil

FOLFOX

Drug: Leucovorin

FOLFOX

Drug: Oxaliplatin

FOLFOX

Experimental: Cohort B: Second Line or greater Checkpoint Inhibitor Naïve Participants

Domvanalimab and zimberelimab will be administered by IV infusion

Drug: Zimberelimab

Zimberelimab is an anti-PD-1 monoclonal antibody

Drug: Domvanalimab

Domvanalimab is an anti-TIGIT monoclonal antibody

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

Domvanalimab and zimberelimab will be administered by IV infusion

Drug: Zimberelimab

Zimberelimab is an anti-PD-1 monoclonal antibody

Drug: Domvanalimab

Domvanalimab is an anti-TIGIT monoclonal antibody

Outcome Measures

Primary Outcome Measures

Incidence and severity of adverse events (AEs) and serious adverse events (SAEs) [Up to 18 months]
Objective Response Rate as measured by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 [Up to 18 months]

Secondary Outcome Measures

Objective Response Rate as measured by PD-L1 Expression Level [Up to 18 months]
Overall survival [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]
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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Participants with histologically confirmed diagnosis of locally advanced unresectable or metastatic esophageal, GEJ, or gastric 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 symptomatic, actively progressing, or untreated CNS (brain or leptomeningeal) metastases.
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.
Use of any live vaccines against infectious diseases within 28 days prior to enrollment.