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
210
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
210 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
June 1, 2026
ExpectedStudy Completion
Last participant's last visit for all outcomes
June 1, 2026
April 2, 2026
April 1, 2025
3.5 years
October 3, 2022
March 31, 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
Oral Tablets
IV Aqueous Solution
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 (210)
Genesis Cancer Center and Blood Institute - Hot Springs
Hot Springs, Arkansas, 71913, United States
Kaiser Permanente - Los Angeles Medical Center
Los Angeles, California, 90027, United States
Norris Comprehensive Cancer Center
Los Angeles, California, 90033, United States
University of California Irvine Health Chao Family Comprehensive Cancer Center
Orange, California, 92868, United States
UCLA Health - Santa Monica Cancer Care
Santa Monica, California, 90404, United States
Yale Cancer Center
New Haven, Connecticut, 06520, United States
Georgetown Lombardi Comprehensive Cancer Center
Washington D.C., District of Columbia, 22057, United States
SCRI - Florida Cancer Specialists - South Region Research Office
Fort Myers, Florida, 33901, United States
SCRI - Florida Cancer Specialists - North Region Research Office
St. Petersburg, Florida, 33705, United States
SCRI - Florida Cancer Specialists - Panhandle Research Office
Tallahassee, Florida, 32308, United States
SCRI - Florida Cancer Specialists - East Region Research Office
West Palm Beach, Florida, 33401, United States
University of Louisville James Graham Brown Cancer Center
Louisville, Kentucky, 40202, United States
Norton Cancer Institute - Poplar Level Road
Louisville, Kentucky, 40217, United States
Ochsner Cancer Institute
New Orleans, Louisiana, 70121, United States
Massachusetts General Hospital
Boston, Massachusetts, 02114, United States
University of Michigan Rogel Cancer Center
Ann Arbor, Michigan, 48109, United States
HealthPartners Cancer Center at Regions Hospital
Saint Louis Park, Minnesota, 55426, United States
Regions Hospital
Saint Louis Park, Minnesota, 55426, United States
Perlmutter Cancer Ctr NYU
Mineola, New York, 11501, United States
Perlmutter Cancer Center - 38th Street
New York, New York, 10016, United States
Memorial Sloan Kettering Cancer Center - New York
New York, New York, 10065, United States
Duke University Medical Center
Durham, North Carolina, 27710, United States
Cleveland Clinic - Taussig Cancer Center
Cleveland, Ohio, 44106, United States
University Hospitals Cleveland Medical Center
Cleveland, Ohio, 44106, United States
Cleveland Clin - Fairview Hosp
Cleveland, Ohio, 44111, United States
Mark H. Zangmeister Cancer Center
Columbus, Ohio, 43219, United States
Cleveland Clin-Hillcrest Hosp
Mayfield Heights, Ohio, 44124, United States
Prov Care Clinic - Westside
Portland, Oregon, 97225, United States
Providence Cancer Center Oncology and Hematology Care Westside Portland
Portland, Oregon, 97225, United States
Prisma Health Cancer Institute
Greenville, South Carolina, 29605, United States
Tennessee Oncology - Chattanooga - Memorial Plaza
Nashville, Tennessee, 37203, United States
Tennessee Oncology - Nashville - Centennial
Nashville, Tennessee, 37203, United States
Vanderbilt - Ingram Cancer Center
Nashville, Tennessee, 37232, United States
University of Texas Southwestern Medical Center
Dallas, Texas, 75390, United States
The Center for Cancer & Blood Disorders - Fort Worth
Fort Worth, Texas, 76104, United States
Harris Health System
Houston, Texas, 77054, United States
USOR - Virginia Cancer Specialists - Fairfax Office
Fairfax, Virginia, 22031, United States
Fred Hutchinson Cancer Center - Seattle Cancer Care Alliance (SCCA) Location
Seattle, Washington, 98109, United States
Froedtert Clinical Cancer Center
Milwaukee, Wisconsin, 53226, United States
Hospital Británico de Buenos Aires
Buenos Aires, Argentina
CORI
La Rioja, Argentina
Instituto de Investigaciones Clínicas Mar del Plata
Mar del Plata, Argentina
Monash University
Clayton, Australia
Gosford Hospital
Gosford, Australia
Liverpool Hospital
Liverpool, Australia
Oncology West - Murdoch
Murdoch, Australia
Fundação Pio XII - Hospital de Câncer de Barretos - Hospital de Amor
Barretos, Brazil
ONCOSITE - Centro de Pesquisa Clinica Em Oncologia Ltda.
Ijuí, Brazil
Liga Contra o Câncer - Centro Avançado de Oncologia
Natal, Brazil
Hospital Ernesto Dornelles
Porto Alegre, Brazil
Instituto Nacional de Câncer - Brazil
Rio de Janeiro, Brazil
Queen Elizabeth II Health Sciences Centre-Victoria General
Halifax, Canada
Hôpital Notre-Dame
Montreal, Canada
Ottawa Hospital - General Campus
Ottawa, Canada
Princess Margaret Cancer Centre
Toronto, Canada
Sunnybrook Health Sciences Centre - Bayview Campus
Toronto, Canada
Icegclinic
La Florida, Chile
Hospital Puerto Montt
Port Montt, Chile
Oncovida - Santiago
Providencia, Chile
Bradford Hill Centro de Investigaciones Clinicas
Recoleta, Chile
Centro de Estudios Clínicos SAGA
Santiago, Chile
Pontificia Universidad Catolica de Chile - Escuela De Medicina - Clinica UC San Carlos de Apoq
Santiago, Chile
Clínica Universidad Católica del Maule - Talca
Talca, Chile
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
Zhejiang Cancer Hospital
Hangzhou, China
2nd hosp Anhui Med University
Hefei, China
Anhui Provincial Hospital
Hefei, China
Shanghai East Hospital
Shanghai, China
Tianjin Cancer Hospital
Tianjin, China
Qinghai UNV Afl Hospital
Xining, China
Henan Cancer Hospital
Zhengzhou, China
Institut Bergonié
Bordeaux, France
Hôpital Morvan
Brest, France
Centre de Lutte contre le Cancer - François Baclesse
Caen, France
Hôpital Claude Huriez
Lille, France
Centre Léon Bérard
Lyon, France
Hôpital de la Timone
Marseille, France
Institut Régional du Cancer de Montpellier
Montpellier, France
Centre Armoricain de Radiothérapie, d'Imagerie Médicale et d'Oncologie
Plérin, France
Centre Hospitalier Universitaire de Poitiers
Poitiers, France
CHU de Toulouse - Hopital Rangueil
Toulouse, France
Institut Gustave Roussy
Villejuif, France
Evex Hospitals - Kutaisi Referral Hospital
Kutaisi, 4600, Georgia
LLC Todua Clinic
Tbilisi, 112, Georgia
Ltd Tbilisi State Medical University and Ingorokva High Medical Technology University Clinic
Tbilisi, 144, Georgia
New Vision University Hospital
Tbilisi, 159, Georgia
Multi-profile Clinic "New Hospitals"
Tbilisi, 186, Georgia
Clínica Privada Dr. Rixci Ramírez
Guatemala City, Guatemala
Grupo Medico Angeles
Guatemala City, Guatemala
INTEGRA Cancer Institute
Guatemala City, Guatemala
Medi-k Cayalá
Guatemala City, Guatemala
Centro Regional de Sub Especialidades Médicas (CRESEM) SA
Quetzaltenango, Guatemala
Hong Kong Sanatorium and Hosp
Happy Valley, Hong Kong
Humanity & Health Clinical Trial Centre
Hong Kong, Hong Kong
Queen Mary Hospital - Hong Kong
Hong Kong, Hong Kong
Tuen Mun Hospital
Tuenmen, Hong Kong
Dél-pesti Centrumkórház - Országos Hematológiai és Infektológiai Intézet
Budapest, Hungary
Országos Onkológiai Intézet
Budapest, Hungary
Bács-Kiskun Megyei Oktatókórház - Kecskemét
Kecskemét, Hungary
Pécsi Tudományegyetem Klinikai Központ
Pécs, Hungary
Hadassah University Hospital Ein Kerem
Jerusalem, Israel
Shaare Zedek Medical Center
Jerusalem, Israel
Davidoff Cancer Center
Petah Tikva, Israel
Tel Aviv Sourasky Medical Center
Tel Aviv, Israel
Azienda Ospedaliero - Universitaria Careggi
Florence, Italy
Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) - Ospedale San Raffaele
Milan, Italy
Istituto Europeo di Oncologia
Milan, Italy
Ospedale Santa Maria Croci
Ravenna, Italy
Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) - Istituto Clinico Humanitas
Rozzano, Italy
Azienda Sanitaria Universitaria Friuli Centrale ? P.O. Santa Maria della Misericordia
Udine, Italy
Hyogo Cancer Center
Akashi, Japan
Tokyo Metro Ctr
Bunkyō City, Japan
University of Tokyo Hospital
Bunkyō City, Japan
Chiba Cancer Center
Chiba, Japan
Kyushu Cancer Center
Fukuoka, Japan
Nat Cancer Ctr-Kashiwa Campus
Kashiwa-shi, Japan
St. Marianna Uni Hosp
Kawasaki, Japan
Cancer Inst Hosp of JFCR
Kōtō City, Japan
Kumamoto University Hospital
Kumamoto, Japan
Shikoku Cancer Center
Matsuyama, Japan
Shizuoka Cancer Center
Nagaizumi-cho, Japan
Aichi Cancer Center
Nagoya, Japan
Niigata Cancer Center Hospital
Niigata, Japan
Osaka Prefectural Hosp Org
Osaka, Japan
Kindai University Hospital
Osakasayama-shi, Japan
Gunma Prefectural Cancer Ctr
Ota-shi, Japan
Saitama Cancer Center
Saitama, Japan
National Cancer Ctr Hosp
Tokyo, Japan
Kanagawa Cancer Center
Yokohama, Japan
Kauno Klinikos
Kaunas, Lithuania
Klaipedos Universitetine Ligonine
Klaipėda, Lithuania
Nacionalinis Vėžio Institutas
Vilnius, Lithuania
Vilniaus Universiteto Ligoninė Santariškių Klinikos
Vilnius, Lithuania
Hospital Pulau Pinang
George Town, Malaysia
Hospital Kuala Lumpur
Kuala Lumpur, Malaysia
Pusat Perubatan Universiti Malaya
Kuala Lumpur, Malaysia
Hospital Umum Sarawak
Kuching, Malaysia
CLIMERS Clinical Medical Research
Colonia Centro, 94300, Mexico
Centro Especializado en Investigacion y Tratamiento Oncologicos SC
Mexico City, 3100, Mexico
Centro de Atención e Investigación Clínica en Oncología
Mérida, 97134, Mexico
Hospital Zambrano Hellion TecSalud
San Pedro Garza García, 66278, Mexico
Centro Hemato - Oncológico Privado (CHOP)
Toluca, 50120, Mexico
Hosp Nacional Daniel Carrion
Bellavista, Peru
SANNA - Clínica El Golf
San Isidro, Peru
Hospital Maria Auxiliadora
San Juán de Miraflores, Peru
Instituto Nacional de Enfermedades Neoplásicas
Surquillo, Peru
Dr Pablo O. Torre Memorial Hospital - Riverside Medical Center
Bacolod City, Philippines
Baguio General Hospital and Medical Center
Baguio City, Philippines
Cebu Doctors' University Hospital
Cebu City, Philippines
Manila Doctors Hospital
Manila, Philippines
Centrum Onkologii Ziemi Lubelskiej im. św. Jana z Dukli
Lublin, Poland
Samodzielny Publiczny Szpital Kliniczny nr 1 w Lublinie
Lublin, Poland
Szpital Miejski w Tychach
Tychy, Poland
Narodowy Instytut Onkologii im. Marii Skłodowskiej-Curie - Państwowy Instytut Badawczy
Warsaw, Poland
Centro Hospitalar e Universitário de Coimbra
Coimbra, Portugal
Fundação D. Anna de Sommer Champalimaud e Dr. Carlos Montez Champalimaud
Lisbon, Portugal
Instituto Português de Oncologia do Porto Francisco Gentil
Porto, Portugal
Spitalul Judetean de Urgenta
Baia Mare, Romania
Institutul Clinic Fundeni
Bucharest, Romania
Institutul Oncologic Prof. Dr. Ion Chiricuta
Cluj-Napoca, Romania
Medisprof
Cluj-Napoca, Romania
Centrul De Oncologie Sf Nectarie
Craiova, Romania
Centrul de Radioterapie Amethyst Cluj
Florești, Romania
Centrul de Oncologie Euroclinic
Iași, Romania
Clinica SIGMedical
Suceava, Romania
Institute of Oncology and Radiology of Serbia (Institut za onkologiju i radiologiju Srbije)
Belgrade, Serbia
University Hospital Medical Center (KBC) Bezanijska Kosa
Belgrade, Serbia
Clinical Center Kragujevac
Kragujevac, Serbia
Dong-A University Hospital
Busan, South Korea
Kyungpook Nat Uni Chilgok
Daegu, South Korea
Cha Bundang Medical Center
Seongnam, South Korea
Asan Medical Center
Seoul, South Korea
Korea University Guro Hospital
Seoul, South Korea
Samsung Medical Center
Seoul, South Korea
Seoul Nat Uni Hospital
Seoul, South Korea
Severance Hospital
Seoul, South Korea
Hospital Universitari Vall d'Hebrón
Barcelona, Spain
Institut Català d'Oncologia - Hospital Duran i Reynals (ICO L'Hospitalet)
Barcelona, Spain
Hospital General Universitario Gregorio Marañón
Madrid, Spain
Hospital Universitario HM Sanchinarro
Madrid, Spain
Hospital Universitario Ramón y Cajal
Madrid, Spain
Hospital Universitario Marqués de Valdecilla
Santander, Spain
Hospital Clínico Universitario de Valencia
Valencia, Spain
Hospital Universitario Miguel Servet
Zaragoza, Spain
Faculty of Medicine Siriraj Hospital
Bang Phlat, Thailand
Songklanagarind Hospital
Hat Yai, Thailand
Sunpasitthiprasong Hospital
Ubon Ratchathani, Thailand
T.C. Saglik Bakanligi Adana Sehir Egitim ve Arastirma Hastanesi
Adana, Turkey (Türkiye)
Memorial Ankara Hastanesi
Ankara, Turkey (Türkiye)
Trakya Universitesi Tip Fakultesi
Edirne, Turkey (Türkiye)
T.C. Saglik Bakanligi - Istanbul Il Saglik Mudurlugu - Goztepe Prof. Dr. Suleyman Yalcin Sehir Hastanesi
Istanbul, Turkey (Türkiye)
Kocaeli Üniversitesi Araştırma ve Uygulama Hastanesi
İzmit, Turkey (Türkiye)
Inönü Üniversitesi Turgut Özal Tıp Merkezi
Malatya, Turkey (Türkiye)
Ankara Üniversitesi Tıp Fakültesi - Cebeci Araştırma ve Uygulama Hastanesi
Mamak, Turkey (Türkiye)
Van Yüzüncü Yıl Üniversitesi Dursun Odabaş Tıp Merkezi
Van, Turkey (Türkiye)
Ataturk Universitesi Arastirma Hastanesi
Yakutiye, Turkey (Türkiye)
Başkent Üniversitesi Adana Dr Turgut Noyan Uygulama ve Araştirma Merkezi
Yüreğir, Turkey (Türkiye)
Barts Health NHS Trust
London, United Kingdom
Sarah Cannon Research Institute London
London, United Kingdom
The Royal Marsden NHS Foundation Trust
London, United Kingdom
University College London Hospitals NHS Foundation Trust
London, United Kingdom
The Christie NHS Foundation Trust
Manchester, United Kingdom
Oxford University Hospitals NHS Foundation Trust
Oxford, United Kingdom
The Royal Marsden NHS Foundation Trust
Sutton, United Kingdom
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 (Estimated)
June 1, 2026
Study Completion (Estimated)
June 1, 2026
Last Updated
April 2, 2026
Record last verified: 2025-04
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.