STAR-221: 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

Sponsor

Arcus Biosciences, Inc. (Industry)

Overall Status

Recruiting

CT.gov ID

NCT05568095

Collaborator

Gilead Sciences (Industry)

970

Enrollment

Locations

Arms

49.3

Anticipated Duration (Months)

80.8

Patients Per Site

1.6

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Advanced Upper Gastrointestinal Tract Adenocarcinoma	Drug: Zimberelimab Drug: Domvanalimab Drug: Nivolumab Drug: Oxaliplatin Drug: Leucovorin Drug: Fluorouracil Drug: Capecitabine	Phase 3

Study Design

Study Type:

Interventional

Anticipated Enrollment :

970 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Randomized, Open-Label, Multicenter Phase 3 Trial of Domvanalimab, Zimberelimab, and Chemotherapy Versus Nivolumab and Chemotherapy in Participants With Previously Untreated Locally Advanced Unresectable or Metastatic Gastric, Gastroesophageal Junction, and Esophageal Adenocarcinoma

Actual Study Start Date :

Nov 21, 2022

Anticipated Primary Completion Date :

Sep 1, 2026

Anticipated Study Completion Date :

Jan 1, 2027

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Domvanalimab + Zimberelimab + FOLFOX/CAPOX (PI Choice) 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.	Drug: Zimberelimab Intravenous (IV) Aqueous Solution Other Names: AB122 Drug: Domvanalimab IV Aqueous Solution Other Names: AB154 Drug: Oxaliplatin IV Aqueous Solution Drug: Leucovorin IV Aqueous Solution Drug: Fluorouracil IV Aqueous Solution Drug: Capecitabine Oral Tablets
Active Comparator: Nivolumab + FOLFOX/CAPOX (PI Choice) Participants in this arm will receive Nivolumab Q2W and FOLFOX Q2W or Nivolumab Q3W + CAPOX Q3W.	Drug: Nivolumab IV Aqueous Solution Drug: Oxaliplatin IV Aqueous Solution Drug: Leucovorin IV Aqueous Solution Drug: Fluorouracil IV Aqueous Solution Drug: Capecitabine Oral Tablets

Arm

Intervention/Treatment

Experimental: Domvanalimab + Zimberelimab + FOLFOX/CAPOX (PI Choice)

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.

Drug: Zimberelimab

Intravenous (IV) Aqueous Solution

Other Names:

AB122

Drug: Domvanalimab

IV Aqueous Solution

Other Names:

AB154

Drug: Oxaliplatin

IV Aqueous Solution

Drug: Leucovorin

IV Aqueous Solution

Drug: Fluorouracil

IV Aqueous Solution

Drug: Capecitabine

Oral Tablets

Active Comparator: Nivolumab + FOLFOX/CAPOX (PI Choice)

Participants in this arm will receive Nivolumab Q2W and FOLFOX Q2W or Nivolumab Q3W + CAPOX Q3W.

Drug: Nivolumab

IV Aqueous Solution

Drug: Oxaliplatin

IV Aqueous Solution

Drug: Leucovorin

IV Aqueous Solution

Drug: Fluorouracil

IV Aqueous Solution

Drug: Capecitabine

Oral Tablets

Outcome Measures

Primary Outcome Measures

Overall survival [From randomization until death from any cause (Approximately 15 months)]

Secondary Outcome Measures

Progression-free survival (PFS) [Approximately 15 months]
Objective response rate (ORR) [Approximately 15 months]
Duration of response (DOR) [Approximately 15 months]
Incidence and severity of adverse events (AEs) and serious adverse events (SAEs) [Approximately 15 months]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Age >= 18 years at the time of signing the informed consent.
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 Score of 0-1.
At least one measurable target lesion per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.

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 neoadjuvant or adjuvant chemotherapy.

Other protocol defined Inclusion/Exclusion criteria may apply.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Genesis Cancer and Blood Institute	Hot Springs	Arkansas	United States	71913
2	SCRI - Florida Cancer Specialists - South Region Research Office	Fort Myers	Florida	United States	33901
3	SCRI - Florida Cancer Specialists - North Region Research Office	Saint Petersburg	Florida	United States	33705
4	SCRI - Florida Cancer Specialists - Panhandle Research Office	Tallahassee	Florida	United States	32308
5	SCRI - Florida Cancer Specialists - East Region Research Office	West Palm Beach	Florida	United States	33401
6	Norton Cancer Institute	Louisville	Kentucky	United States	40217
7	HealthPartners Cancer Center at Regions Hospital	Saint Louis Park	Minnesota	United States	55426
8	Mark H. Zangmeister Cancer Center	Columbus	Ohio	United States	43219
9	Prisma Health Cancer Insitute	Greenville	South Carolina	United States	29615
10	SCRI - Tennessee Oncology - Chattanooga - Memorial Plaza	Nashville	Tennessee	United States	37203
11	SCRI - Tennessee Oncology - Nashville - Centennial	Nashville	Tennessee	United States	37203
12	The Center for Cancer & Blood Disorders - Fort Worth	Fort Worth	Texas	United States	76104