A Safety and Efficacy Study of Treatment Combinations With and Without Chemotherapy in Adult Participants With Advanced Upper Gastrointestinal Tract Malignancies
Phase 2
Active, not recruiting
- Conditions
- Gastrointestinal Tract Malignancies
- Interventions
- Registration Number
- NCT05329766
- Lead Sponsor
- Arcus Biosciences, Inc.
- 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).
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 332
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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description A1: First Line - Treatment Naïve Participants Domvanalimab Domvanalimab and zimberelimab once every 4 weeks (Q4W) in addition to FOLFOX chemotherapy by intravenous (IV) infusion once every 2 weeks (Q2W) A2: First Line - Treatment Naïve Participants Zimberelimab Zimberelimab Q4W in addition to chemotherapy with FOLFOX administered by IV infusion Q2W A3 First Line - Treatment Naïve Participants Fluorouracil 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 A4 First Line - Treatment Naïve Participants Zimberelimab Zimberelimab administered Q4W via IV infusion over 30 minutes, in addition to FOLFOX chemotherapy via IV infusion Q2W A4 First Line - Treatment Naïve Participants Oxaliplatin Zimberelimab administered Q4W via IV infusion over 30 minutes, in addition to FOLFOX chemotherapy via IV infusion Q2W B2: Second Line or greater Checkpoint Inhibitor Naïve Participants Quemliclustat Quemliclustat Q2W and zimberelimab Q4W administered by IV infusion B1: Second Line or greater Checkpoint Inhibitor Naïve Participants Domvanalimab Domvanalimab and zimberelimab administered once every three weeks (Q3W) by IV infusion Cohort C1: Second Line or greater - Checkpoint Inhibitor Experienced Participants Domvanalimab Domvanalimab and zimberelimab Q3W administered by IV infusion A3 First Line - Treatment Naïve Participants Domvanalimab 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 A1: First Line - Treatment Naïve Participants Fluorouracil Domvanalimab and zimberelimab once every 4 weeks (Q4W) in addition to FOLFOX chemotherapy by intravenous (IV) infusion once every 2 weeks (Q2W) A1: First Line - Treatment Naïve Participants Zimberelimab Domvanalimab and zimberelimab once every 4 weeks (Q4W) in addition to FOLFOX chemotherapy by intravenous (IV) infusion once every 2 weeks (Q2W) A1: First Line - Treatment Naïve Participants Oxaliplatin Domvanalimab and zimberelimab once every 4 weeks (Q4W) in addition to FOLFOX chemotherapy by intravenous (IV) infusion once every 2 weeks (Q2W) A1: First Line - Treatment Naïve Participants Leucovorin Domvanalimab and zimberelimab once every 4 weeks (Q4W) in addition to FOLFOX chemotherapy by intravenous (IV) infusion once every 2 weeks (Q2W) A2: First Line - Treatment Naïve Participants Fluorouracil Zimberelimab Q4W in addition to chemotherapy with FOLFOX administered by IV infusion Q2W A2: First Line - Treatment Naïve Participants Oxaliplatin Zimberelimab Q4W in addition to chemotherapy with FOLFOX administered by IV infusion Q2W A2: First Line - Treatment Naïve Participants Leucovorin Zimberelimab Q4W in addition to chemotherapy with FOLFOX administered by IV infusion Q2W A3 First Line - Treatment Naïve Participants Zimberelimab 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 A3 First Line - Treatment Naïve Participants Leucovorin 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 A3 First Line - Treatment Naïve Participants Oxaliplatin 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 A4 First Line - Treatment Naïve Participants Fluorouracil Zimberelimab administered Q4W via IV infusion over 30 minutes, in addition to FOLFOX chemotherapy via IV infusion Q2W A4 First Line - Treatment Naïve Participants Leucovorin Zimberelimab administered Q4W via IV infusion over 30 minutes, in addition to FOLFOX chemotherapy via IV infusion Q2W B2: Second Line or greater Checkpoint Inhibitor Naïve Participants Zimberelimab Quemliclustat Q2W and zimberelimab Q4W administered by IV infusion B1: Second Line or greater Checkpoint Inhibitor Naïve Participants Zimberelimab Domvanalimab and zimberelimab administered once every three weeks (Q3W) by IV infusion Cohort C1: Second Line or greater - Checkpoint Inhibitor Experienced Participants Zimberelimab Domvanalimab and zimberelimab Q3W administered by IV infusion
- Primary Outcome Measures
Name Time Method Number of Participants with Adverse Events (AEs) Up to 18 months Objective Response Rate (ORR) as measured by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 Up to 18 months
- Secondary Outcome Measures
Name Time Method 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
Trial Locations
- Locations (49)
Mayo Clinic - Arizona
🇺🇸Phoenix, Arizona, United States
USC/Norris Comprehensive Cancer Center
🇺🇸Los Angeles, California, United States
Ronald Reagan UCLA Medical Center
🇺🇸Santa Monica, California, United States
Yale Cancer Center
🇺🇸Derby, Connecticut, United States
Florida Cancer Specialist - South
🇺🇸Fort Myers, Florida, United States
Mayo Clinic - Jacksonville
🇺🇸Jacksonville, Florida, United States
Florida Cancer Specialist - North
🇺🇸Saint Petersburg, Florida, United States
Massachusetts General Hospital
🇺🇸Boston, Massachusetts, United States
Memorial Sloan Kettering Cancer Center
🇺🇸New York, New York, United States
Columbia University
🇺🇸New York, New York, United States
Scroll for more (39 remaining)Mayo Clinic - Arizona🇺🇸Phoenix, Arizona, United States