A Clinical Trial of a New Combination Treatment, Domvanalimab and Zimberelimab, Plus Chemotherapy, for People With an Upper Gastrointestinal Tract Cancer That Cannot be Removed With Surgery That Has Spread to Other Parts of the Body
Phase 3
Active, not recruiting
- Conditions
- Advanced Upper Gastrointestinal Tract Adenocarcinoma
- Interventions
- Registration Number
- NCT05568095
- Lead Sponsor
- Arcus Biosciences, Inc.
- Brief Summary
This randomized Phase 3 open-label study will compare the efficacy of the T-cell immunoglobulin and immunoreceptor tyrosine-based inhibitory motif (ITIM) domain (TIGIT) monoclonal antibody domvanalimab, the anti programmed cell death protein 1 (PD-1) monoclonal antibody zimberelimab, and multiagent chemotherapy versus the anti PD-1 monoclonal antibody nivolumab and multiagent chemotherapy in the first-line treatment of participants with locally advanced unresectable or metastatic gastric, gastroesophageal junction (GEJ), and esophageal adenocarcinoma.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 1040
Inclusion Criteria
- Capable of giving signed informed consent which is in compliance with the requirements and restrictions listed in the informed consent form (ICF) and in protocol.
- Histologically confirmed diagnosis of locally advanced unresectable or metastatic gastric, GEJ, or esophageal adenocarcinoma.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.
- At least one measurable target lesion per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.
Key
Exclusion Criteria
- Underlying medical or psychiatric conditions that, in the investigator's or sponsor's opinion, will make the administration of study-specified therapy hazardous, including but not limited to:
- Interstitial lung disease, including history of interstitial lung disease or non-infectious pneumonitis. Active viral, bacterial, or fungal infections requiring parenteral treatment within 14 days of randomization.
- Clinically significant cardiovascular disease, such as New York Heart Association Class II or greater cardiac disease or cerebrovascular accident within 3 months prior to randomization, unstable angina, or new onset angina within 3 months prior to randomization, myocardial infarction within 6 months prior to randomization, or unstable arrhythmia within 3 months prior to randomization.
- History of prior solid-organ transplantation, including allogenic bone marrow transplantation.
- Dementia, psychiatric, or substance abuse disorders that would interfere with satisfying the requirements of the trial.
- Known human epidermal growth factor receptor 2 (HER-2) positive tumor.
- Known untreated, symptomatic, or actively progressing central nervous system (CNS) (brain) metastases. Participants with leptomeningeal metastases are excluded from enrollment.
- Received prior systemic treatment for locally advanced unresectable or metastatic gastric, GEJ, or esophageal adenocarcinoma.
- Disease progression within 6 months of completion of neoadjuvant or adjuvant therapy.
Note: Other protocol defined Inclusion/Exclusion criteria may apply.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Domvanalimab + Zimberelimab + FOLFOX/CAPOX (PI Choice) Domvanalimab Participants in this arm will receive Domvanalimab and zimberelimab doses once every 4 weeks (Q4W) in addition to chemotherapy with FOLFOX (oxaliplatin, leucovorin, fluorouracil) once every 2 weeks (Q2W) or Domvanalimab and zimberelimab once every 3 weeks (Q3W) in addition to chemotherapy with CAPOX (capecitabine and oxaliplatin) Q3W. Nivolumab + FOLFOX/CAPOX (PI Choice) Fluorouracil Participants in this arm will receive Nivolumab Q2W and FOLFOX Q2W or Nivolumab Q3W + CAPOX Q3W. Domvanalimab + Zimberelimab + FOLFOX/CAPOX (PI Choice) Oxaliplatin Participants in this arm will receive Domvanalimab and zimberelimab doses once every 4 weeks (Q4W) in addition to chemotherapy with FOLFOX (oxaliplatin, leucovorin, fluorouracil) once every 2 weeks (Q2W) or Domvanalimab and zimberelimab once every 3 weeks (Q3W) in addition to chemotherapy with CAPOX (capecitabine and oxaliplatin) Q3W. Domvanalimab + Zimberelimab + FOLFOX/CAPOX (PI Choice) Zimberelimab Participants in this arm will receive Domvanalimab and zimberelimab doses once every 4 weeks (Q4W) in addition to chemotherapy with FOLFOX (oxaliplatin, leucovorin, fluorouracil) once every 2 weeks (Q2W) or Domvanalimab and zimberelimab once every 3 weeks (Q3W) in addition to chemotherapy with CAPOX (capecitabine and oxaliplatin) Q3W. Domvanalimab + Zimberelimab + FOLFOX/CAPOX (PI Choice) Capecitabine Participants in this arm will receive Domvanalimab and zimberelimab doses once every 4 weeks (Q4W) in addition to chemotherapy with FOLFOX (oxaliplatin, leucovorin, fluorouracil) once every 2 weeks (Q2W) or Domvanalimab and zimberelimab once every 3 weeks (Q3W) in addition to chemotherapy with CAPOX (capecitabine and oxaliplatin) Q3W. Domvanalimab + Zimberelimab + FOLFOX/CAPOX (PI Choice) Fluorouracil Participants in this arm will receive Domvanalimab and zimberelimab doses once every 4 weeks (Q4W) in addition to chemotherapy with FOLFOX (oxaliplatin, leucovorin, fluorouracil) once every 2 weeks (Q2W) or Domvanalimab and zimberelimab once every 3 weeks (Q3W) in addition to chemotherapy with CAPOX (capecitabine and oxaliplatin) Q3W. Domvanalimab + Zimberelimab + FOLFOX/CAPOX (PI Choice) Leucovorin Participants in this arm will receive Domvanalimab and zimberelimab doses once every 4 weeks (Q4W) in addition to chemotherapy with FOLFOX (oxaliplatin, leucovorin, fluorouracil) once every 2 weeks (Q2W) or Domvanalimab and zimberelimab once every 3 weeks (Q3W) in addition to chemotherapy with CAPOX (capecitabine and oxaliplatin) Q3W. Nivolumab + FOLFOX/CAPOX (PI Choice) Capecitabine Participants in this arm will receive Nivolumab Q2W and FOLFOX Q2W or Nivolumab Q3W + CAPOX Q3W. Nivolumab + FOLFOX/CAPOX (PI Choice) Leucovorin Participants in this arm will receive Nivolumab Q2W and FOLFOX Q2W or Nivolumab Q3W + CAPOX Q3W. Nivolumab + FOLFOX/CAPOX (PI Choice) Oxaliplatin Participants in this arm will receive Nivolumab Q2W and FOLFOX Q2W or Nivolumab Q3W + CAPOX Q3W. Nivolumab + FOLFOX/CAPOX (PI Choice) Nivolumab Participants in this arm will receive Nivolumab Q2W and FOLFOX Q2W or Nivolumab Q3W + CAPOX Q3W.
- Primary Outcome Measures
Name Time Method Overall survival From date of randomization until date of death from any cause (Approximately 15 months)]
- Secondary Outcome Measures
Name Time Method Objective response rate (ORR) Proportion of randomized participants who achieved a confirmed best overall response of complete response (CR) or partial response (PR) (Approximately 15 months) Duration of response (DOR) From the date of first confirmed response (CR or PR), until the date of first documented disease progression or date of death from any cause, whichever comes first (Approximately 15 months) Incidence and severity of adverse events (AEs) and serious adverse events (SAEs) From on or after the date of first dose of any study treatment to the date of last study treatment specific safety follow-up or date of initiation of subsequent systemic anti-cancer therapy, whichever occurs first (Approximately 15 months) Time to first symptom deterioration in the FACT-Ga gastric cancer subscale. From the date of randomization to change from baseline in subscale greater than or equal to the deterioration threshold, or death from any cause, whichever comes first (Approximately 15 months) Progression-free survival (PFS) From date of randomization to date of the first documentation of disease progression or date of death from any cause, whichever comes first (Approximately 15 months)
Trial Locations
- Locations (209)
Cleveland Clinic - Taussig Cancer Center
🇺🇸Cleveland, Ohio, United States
Prisma Health Cancer Institute
🇺🇸Greenville, South Carolina, United States
CORI
🇦🇷La Rioja, Argentina
1st Hosp of Jilin University
🇨🇳Changchun, China
1st People's Hosp of Changzhou
🇨🇳Changzhou, China
900 Hospital
🇨🇳Fuzhou, China
Guangdong PR People's Hospital
🇨🇳Guangzhou, China
Sun Yat-Sen Cancer Center
🇨🇳Guangzhou, China
Hainan General Hospital
🇨🇳Haikou, China
Sir Run Run Shaw Hospital
🇨🇳Hangzhou, China
Scroll for more (199 remaining)Cleveland Clinic - Taussig Cancer Center🇺🇸Cleveland, Ohio, United States