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
STAR-221
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
6 other identifiers
interventional
1,040
29 countries
168
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_3
Started Nov 2022
Typical duration for phase_3
168 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
October 3, 2022
CompletedFirst Posted
Study publicly available on registry
October 5, 2022
CompletedStudy Start
First participant enrolled
November 21, 2022
CompletedPrimary Completion
Last participant's last visit for primary outcome
August 1, 2026
CompletedStudy Completion
Last participant's last visit for all outcomes
August 1, 2026
CompletedJuly 31, 2026
May 1, 2026
3.7 years
October 3, 2022
July 29, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Overall survival
From date of randomization until date of death from any cause (Approximately 15 months)]
Secondary Outcomes (5)
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)
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)
Study Arms (2)
Domvanalimab + Zimberelimab + FOLFOX/CAPOX (PI Choice)
EXPERIMENTALParticipants 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)
ACTIVE COMPARATORParticipants in this arm will receive Nivolumab Q2W and FOLFOX Q2W or Nivolumab Q3W + CAPOX Q3W.
Interventions
Intravenous (IV) Aqueous Solution
IV Aqueous Solution
IV Aqueous Solution
Oral Tablets
IV Aqueous Solution
IV Aqueous Solution
Eligibility Criteria
You may qualify if:
- 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.
You may not qualify if:
- 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.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Arcus Biosciences, Inc.lead
- Gilead Sciencescollaborator
- Taiho Pharmaceutical Co., Ltd.collaborator
Study Sites (168)
Research Site
Los Angeles, California, 90033, United States
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Orange, California, 92868, United States
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Santa Monica, California, 90404, United States
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New Haven, Connecticut, 06520, United States
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Washington D.C., District of Columbia, 22057, United States
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Fort Myers, Florida, 33901, United States
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St. Petersburg, Florida, 33705, United States
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Tallahassee, Florida, 32308, United States
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Louisville, Kentucky, 40202, United States
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Louisville, Kentucky, 40217, United States
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New Orleans, Louisiana, 70121, United States
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Boston, Massachusetts, 02114, United States
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Ann Arbor, Michigan, 48109, United States
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Saint Louis Park, Minnesota, 55426, United States
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Mineola, New York, 11501, United States
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New York, New York, 10016, United States
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New York, New York, 10065, United States
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Durham, North Carolina, 27710, United States
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Cleveland, Ohio, 44106, United States
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Cleveland, Ohio, 44111, United States
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Columbus, Ohio, 43219, United States
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Mayfield Heights, Ohio, 44124, United States
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Portland, Oregon, 97225, United States
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Nashville, Tennessee, 37203, United States
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Nashville, Tennessee, 37232, United States
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Dallas, Texas, 75390, United States
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Fort Worth, Texas, 76104, United States
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Houston, Texas, 77054, United States
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Fairfax, Virginia, 22031, United States
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Seattle, Washington, 98109, United States
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Milwaukee, Wisconsin, 53226, United States
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Buenos Aires, Argentina
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La Rioja, Argentina
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Mar del Plata, Argentina
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Clayton, Australia
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Murdoch, Australia
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Barretos, Brazil
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Ijuí, Brazil
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Natal, Brazil
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Porto Alegre, Brazil
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Halifax, Canada
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Montreal, Canada
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Ottawa, Canada
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Toronto, Canada
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La Florida, Chile
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Port Montt, Chile
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Providencia, Chile
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Recoleta, Chile
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Santiago, Chile
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Talca, Chile
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Changchun, China
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Changzhou, China
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Fuzhou, China
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Guangzhou, China
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Haikou, China
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Hangzhou, China
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Hefei, China
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Shanghai, China
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Tianjin, China
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Zhengzhou, China
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Bordeaux, France
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Brest, France
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Caen, France
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Lille, France
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Lyon, France
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Montpellier, France
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Plérin, France
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Poitiers, France
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Toulouse, France
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Villejuif, France
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Kutaisi, 4600, Georgia
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Tbilisi, 112, Georgia
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Tbilisi, 144, Georgia
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Tbilisi, 159, Georgia
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Tbilisi, 186, Georgia
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Guatemala City, Guatemala
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Quetzaltenango, Guatemala
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Happy Valley, Hong Kong
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Hong Kong, Hong Kong
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Tuenmen, Hong Kong
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Budapest, Hungary
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Kecskemét, Hungary
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Pécs, Hungary
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Jerusalem, Israel
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Petah Tikva, Israel
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Tel Aviv, Israel
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Florence, Italy
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Milan, Italy
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Milan, Italy
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Ravenna, Italy
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Rozzano, Italy
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Udine, Italy
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Akashi, Japan
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Bunkyō City, Japan
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Chiba, Japan
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Fukuoka, Japan
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Kashiwa-shi, Japan
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Kawasaki, Japan
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Kōtō City, Japan
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Matsuyama, Japan
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Nagaizumi-cho, Japan
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Nagoya, Japan
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Niigata, Japan
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Osaka, Japan
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Osakasayama-shi, Japan
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Ota-shi, Japan
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Saitama, Japan
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Tokyo, Japan
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Yokohama, Japan
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Kaunas, Lithuania
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Klaipėda, Lithuania
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Vilnius, Lithuania
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George Town, Malaysia
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Kuala Lumpur, Malaysia
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Kuching, Malaysia
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Colonia Centro, 94300, Mexico
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Mexico City, 3100, Mexico
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Mérida, 97134, Mexico
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San Pedro Garza García, 66278, Mexico
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Toluca, 50120, Mexico
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San Isidro, Peru
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San Juán de Miraflores, Peru
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Surquillo, Peru
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Bacolod City, Philippines
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Baguio City, Philippines
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Cebu City, Philippines
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Manila, Philippines
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Lublin, Poland
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Tychy, Poland
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Warsaw, Poland
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Coimbra, Portugal
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Lisbon, Portugal
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Porto, Portugal
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Baia Mare, Romania
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Bucharest, Romania
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Cluj-Napoca, Romania
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Craiova, Romania
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Florești, Romania
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Iași, Romania
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Suceava, Romania
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Belgrade, Serbia
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Kragujevac, Serbia
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Busan, South Korea
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Daegu, South Korea
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Seongnam, South Korea
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Seoul, South Korea
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Barcelona, Spain
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Madrid, Spain
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Santander, Spain
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Valencia, Spain
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Zaragoza, Spain
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Bang Phlat, Thailand
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Hat Yai, Thailand
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Ubon Ratchathani, Thailand
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Adana, Turkey (Türkiye)
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Ankara, Turkey (Türkiye)
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Edirne, Turkey (Türkiye)
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Istanbul, Turkey (Türkiye)
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İzmit, Turkey (Türkiye)
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Malatya, Turkey (Türkiye)
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Mamak, Turkey (Türkiye)
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Van, Turkey (Türkiye)
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Yakutiye, Turkey (Türkiye)
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Yüreğir, Turkey (Türkiye)
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London, United Kingdom
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Manchester, United Kingdom
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Oxford, United Kingdom
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Sutton, United Kingdom
Related Publications (1)
Yu J, Mehta R. Biomarker-Driven Approach to the Treatment of Metastatic Gastric or Gastroesophageal Adenocarcinoma. J Natl Compr Canc Netw. 2025 May;23(5):e257036. doi: 10.6004/jnccn.2025.7036.
PMID: 40341124DERIVED
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- STUDY DIRECTOR
Medical Director
Arcus Biosciences
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
October 3, 2022
First Posted
October 5, 2022
Study Start
November 21, 2022
Primary Completion
August 1, 2026
Study Completion
August 1, 2026
Last Updated
July 31, 2026
Record last verified: 2026-05
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, SAP, CSR
Arcus will provide access to individual de-identified participant data and related study documents \[e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)\] upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. For more information, please visit our website.