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

NCT ID: NCT05568095

Last Updated: 2025-12-23

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE3
• Total Enrollment: 1040 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-11-21
• Study Completion Date: 2026-06-30

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.

Conditions

Advanced Upper Gastrointestinal Tract Adenocarcinoma

Keywords

Domvanalimab; Zimberelimab; Nivolumab; Advanced upper gastrointestinal tract adenocarcinoma; Gastroesophageal junction cancer; Esophageal adenocarcinoma; Gastric cancer; Gastric adenocarcinoma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Domvanalimab

Intervention Type: DRUG

Intravenous (IV) Aqueous Solution

Zimberelimab

Intervention Type: DRUG

IV Aqueous Solution

Capecitabine

Intervention Type: DRUG

Oral Tablets

Fluorouracil

Intervention Type: DRUG

IV Aqueous Solution

Leucovorin

Intervention Type: DRUG

IV Aqueous Solution

Oxaliplatin

Intervention Type: DRUG

IV Aqueous Solution

Nivolumab + FOLFOX/CAPOX (PI Choice)

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

Group Type: ACTIVE_COMPARATOR

Capecitabine

Intervention Type: DRUG

Oral Tablets

Fluorouracil

Intervention Type: DRUG

IV Aqueous Solution

Leucovorin

Intervention Type: DRUG

IV Aqueous Solution

Oxaliplatin

Intervention Type: DRUG

IV Aqueous Solution

Nivolumab

Intervention Type: DRUG

IV Aqueous Solution

Interventions

Domvanalimab

Intravenous (IV) Aqueous Solution

Intervention Type: DRUG

Zimberelimab

IV Aqueous Solution

Intervention Type: DRUG

Capecitabine

Oral Tablets

Intervention Type: DRUG

Fluorouracil

IV Aqueous Solution

Intervention Type: DRUG

Leucovorin

IV Aqueous Solution

Intervention Type: DRUG

Oxaliplatin

IV Aqueous Solution

Intervention Type: DRUG

Nivolumab

IV Aqueous Solution

Intervention Type: DRUG

Other Intervention Names

AB154; AB122

Eligibility Criteria

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.

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Gilead Sciences

INDUSTRY

Sponsor Role: collaborator

Taiho Pharmaceutical Co., Ltd.

INDUSTRY

Sponsor Role: collaborator

Arcus Biosciences, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Medical Director

Role: STUDY_DIRECTOR

Arcus Biosciences

Locations

Genesis Cancer Center and Blood Institute - Hot Springs

Hot Springs, Arkansas, United States

Kaiser Permanente - Los Angeles Medical Center

Los Angeles, California, United States

Norris Comprehensive Cancer Center

Los Angeles, California, United States

University of California Irvine Health Chao Family Comprehensive Cancer Center

Orange, California, United States

UCLA Health - Santa Monica Cancer Care

Santa Monica, California, United States

Yale Cancer Center

New Haven, Connecticut, United States

Georgetown Lombardi Comprehensive Cancer Center

Washington D.C., District of Columbia, United States

SCRI - Florida Cancer Specialists - South Region Research Office

Fort Myers, Florida, United States

SCRI - Florida Cancer Specialists - North Region Research Office

St. Petersburg, Florida, United States

SCRI - Florida Cancer Specialists - Panhandle Research Office

Tallahassee, Florida, United States

SCRI - Florida Cancer Specialists - East Region Research Office

West Palm Beach, Florida, United States

University of Louisville James Graham Brown Cancer Center

Louisville, Kentucky, United States

Norton Cancer Institute - Poplar Level Road

Louisville, Kentucky, United States

Ochsner Cancer Institute

New Orleans, Louisiana, United States

Massachusetts General Hospital

Boston, Massachusetts, United States

University of Michigan Rogel Cancer Center

Ann Arbor, Michigan, United States

HealthPartners Cancer Center at Regions Hospital

Saint Louis Park, Minnesota, United States

Regions Hospital

Saint Louis Park, Minnesota, United States

Perlmutter Cancer Ctr NYU

Mineola, New York, United States

Perlmutter Cancer Center - 38th Street

New York, New York, United States

Memorial Sloan Kettering Cancer Center - New York

New York, New York, United States

Duke University Medical Center

Durham, North Carolina, United States

Cleveland Clinic - Taussig Cancer Center

Cleveland, Ohio, United States

University Hospitals Cleveland Medical Center

Cleveland, Ohio, United States

Cleveland Clin - Fairview Hosp

Cleveland, Ohio, United States

Mark H. Zangmeister Cancer Center

Columbus, Ohio, United States

Cleveland Clin-Hillcrest Hosp

Mayfield Heights, Ohio, United States

Prov Care Clinic - Westside

Portland, Oregon, United States

Providence Cancer Center Oncology and Hematology Care Westside Portland

Portland, Oregon, United States

Prisma Health Cancer Institute

Greenville, South Carolina, United States

Tennessee Oncology - Chattanooga - Memorial Plaza

Nashville, Tennessee, United States

Tennessee Oncology - Nashville - Centennial

Nashville, Tennessee, United States

Vanderbilt - Ingram Cancer Center

Nashville, Tennessee, United States

University of Texas Southwestern Medical Center

Dallas, Texas, United States

The Center for Cancer & Blood Disorders - Fort Worth

Fort Worth, Texas, United States

Harris Health System

Houston, Texas, United States

USOR - Virginia Cancer Specialists - Fairfax Office

Fairfax, Virginia, United States

Fred Hutchinson Cancer Center - Seattle Cancer Care Alliance (SCCA) Location

Seattle, Washington, United States

Froedtert Clinical Cancer Center

Milwaukee, Wisconsin, 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, , Georgia

LLC Todua Clinic

Tbilisi, , Georgia

Ltd Tbilisi State Medical University and Ingorokva High Medical Technology University Clinic

Tbilisi, , Georgia

New Vision University Hospital

Tbilisi, , Georgia

Multi-profile Clinic "New Hospitals"

Tbilisi, , 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, , Mexico

Centro Especializado en Investigacion y Tratamiento Oncologicos SC

Mexico City, , Mexico

Centro de Atención e Investigación Clínica en Oncología

Mérida, , Mexico

Hospital Zambrano Hellion TecSalud

San Pedro Garza García, , Mexico

Centro Hemato - Oncológico Privado (CHOP)

Toluca, , 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

Countries

Greece; United States; Argentina; Australia; Brazil; Canada; Chile; China; France; Georgia; Guatemala; Hong Kong; Hungary; Israel; Italy; Japan; Lithuania; Malaysia; Mexico; Peru; Philippines; Poland; Portugal; Romania; Serbia; South Korea; Spain; Thailand; Turkey (Türkiye); United Kingdom

Related Links

https://trials.arcusbio.com/study/?id=STAR-221

STAR-221 Public Website

Other Identifiers

jRCT2051220179

Identifier Type: REGISTRY

Identifier Source: secondary_id

MOH_2023-04-30_012590

Identifier Type: REGISTRY

Identifier Source: secondary_id

CTR20233469

Identifier Type: REGISTRY

Identifier Source: secondary_id

CTR20233470

Identifier Type: REGISTRY

Identifier Source: secondary_id

2023-507522-16-00

Identifier Type: OTHER

Identifier Source: secondary_id

STAR-221

Identifier Type: -

Identifier Source: org_study_id