Advanced Upper Gastrointestinal Tract AdenocarcinomaPhase 3STAR-221NCT05568095
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
A Phase 3 study testing Domvanalimab, Zimberelimab and Capecitabine in people with Advanced Upper Gastrointestinal Tract Adenocarcinoma, run by Arcus Biosciences, Inc. at 168 sites in 29 countries.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Advanced Upper Gastrointestinal Tract Adenocarcinoma
- What is being tested?
- Domvanalimab, Zimberelimab and Capecitabine
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 1,040 participants
- Where
- 168 sitesin 29 countries
- Study dates
- 21 Nov 2022to 28 Aug 2026
- Phase
- Phase 3
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
168 sites in 29 countries.
168 sites in 29 countries
United States31 sites
Research Site
Ann Arbor, Michigan, 48109
Research Site
Boston, Massachusetts, 02114
Research Site
Cleveland, Ohio, 44106
Research Site
Cleveland, Ohio, 44111
Research Site
Columbus, Ohio, 43219
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Dallas, Texas, 75390
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Durham, North Carolina, 27710
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Fairfax, Virginia, 22031
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Fort Myers, Florida, 33901
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Fort Worth, Texas, 76104
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Houston, Texas, 77054
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Los Angeles, California, 90033
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Louisville, Kentucky, 40202
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Louisville, Kentucky, 40217
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Mayfield Heights, Ohio, 44124
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Milwaukee, Wisconsin, 53226
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Mineola, New York, 11501
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Nashville, Tennessee, 37203
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Nashville, Tennessee, 37232
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New Haven, Connecticut, 06520
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New Orleans, Louisiana, 70121
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New York, New York, 10016
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New York, New York, 10065
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Orange, California, 92868
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Portland, Oregon, 97225
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Saint Louis Park, Minnesota, 55426
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Santa Monica, California, 90404
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Seattle, Washington, 98109
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St. Petersburg, Florida, 33705
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Tallahassee, Florida, 32308
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Washington D.C., District of Columbia, 22057
Japan17 sites
Research Site
Akashi
Research Site
Bunkyō City
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Chiba
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Fukuoka
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Kashiwa-shi
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Kawasaki
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Kōtō City
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Matsuyama
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Nagaizumi-cho
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Nagoya
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Niigata
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Osaka
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Osakasayama-shi
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Ota-shi
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Saitama
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Tokyo
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Yokohama
China10 sites
Research Site
Changchun
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Changzhou
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Fuzhou
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Guangzhou
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Haikou
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Hangzhou
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Hefei
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Shanghai
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Tianjin
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Zhengzhou
France10 sites
Research Site
Bordeaux
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Brest
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Caen
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Lille
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Lyon
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Montpellier
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Plérin
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Poitiers
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Toulouse
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Villejuif
Turkey (Türkiye)10 sites
Research Site
Adana
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Ankara
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Edirne
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Istanbul
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İzmit
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Malatya
Research Site
Mamak
Research Site
Van
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Yakutiye
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Yüreğir
Romania7 sites
Research Site
Baia Mare
Research Site
Bucharest
Research Site
Cluj-Napoca
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Craiova
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Florești
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Iași
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Suceava
Chile6 sites
Research Site
La Florida
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Port Montt
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Providencia
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Recoleta
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Santiago
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Talca
Italy6 sites
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Florence
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Milan
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Milan
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Ravenna
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Rozzano
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Udine
Georgia5 sites
Research Site
Kutaisi, 4600
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Tbilisi, 112
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Tbilisi, 144
Research Site
Tbilisi, 159
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Tbilisi, 186
Mexico5 sites
Research Site
Colonia Centro, 94300
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Mérida, 97134
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Mexico City, 3100
Research Site
San Pedro Garza García, 66278
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Toluca, 50120
Spain5 sites
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Barcelona
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Madrid
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Santander
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Valencia
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Zaragoza
Brazil4 sites
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Barretos
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Ijuí
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Natal
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Porto Alegre
Canada4 sites
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Halifax
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Montreal
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Ottawa
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Toronto
Philippines4 sites
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Bacolod City
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Baguio City
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Cebu City
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Manila
South Korea4 sites
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Busan
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Daegu
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Seongnam
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Seoul
United Kingdom4 sites
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London
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Manchester
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Oxford
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Sutton
Argentina3 sites
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Buenos Aires
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La Rioja
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Mar del Plata
Hong Kong3 sites
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Happy Valley
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Hong Kong
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Tuenmen
Hungary3 sites
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Budapest
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Kecskemét
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Pécs
Israel3 sites
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Jerusalem
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Petah Tikva
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Tel Aviv
Lithuania3 sites
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Kaunas
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Klaipėda
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Vilnius
Malaysia3 sites
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George Town
Research Site
Kuala Lumpur
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Kuching
Peru3 sites
Research Site
San Isidro
Research Site
San Juán de Miraflores
Research Site
Surquillo
Thailand3 sites
Research Site
Bang Phlat
Research Site
Hat Yai
Research Site
Ubon Ratchathani
About this study
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
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.
- Being tested
- Domvanalimab, Zimberelimab, Capecitabine, Fluorouracil, Leucovorin
- Keywords
- Domvanalimab, Zimberelimab, Nivolumab, Advanced upper gastrointestinal tract adenocarcinoma, Gastroesophageal junction cancer, Esophageal adenocarcinoma, Gastric cancer, Gastric adenocarcinoma
- Medical subject headings
- Adenocarcinoma Of Esophagus, Stomach Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DomvanalimabDrug
Also called AB154
Intravenous (IV) Aqueous Solution
ZimberelimabDrug
Also called AB122
IV Aqueous Solution
CapecitabineDrug
Oral Tablets
FluorouracilDrug
IV Aqueous Solution
LeucovorinDrug
IV Aqueous Solution
OxaliplatinDrug
IV Aqueous Solution
NivolumabDrug
IV Aqueous Solution
| Study group | Role | What they receive |
|---|---|---|
| Domvanalimab + Zimberelimab + FOLFOX/CAPOX (PI Choice) | Experimental | 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. Receives: Drug: Domvanalimab; Drug: Zimberelimab; Drug: Capecitabine; Drug: Fluorouracil; Drug: Leucovorin; Drug: Oxaliplatin |
| Nivolumab + FOLFOX/CAPOX (PI Choice) | Active comparator | Participants in this arm will receive Nivolumab Q2W and FOLFOX Q2W or Nivolumab Q3W + CAPOX Q3W. Receives: Drug: Capecitabine; Drug: Fluorouracil; Drug: Leucovorin; Drug: Oxaliplatin; Drug: Nivolumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall survival
Measured: From date of randomization until date of death from any cause (Approximately 15 months)]
Secondary outcomes (5)
Progression-free survival (PFS)
Measured: 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)
Measured: 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)
Measured: 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)
Measured: 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.
Measured: 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)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Oct 2022
- Study start21 Nov 2022
- Primary completion28 Aug 2026
- Study completion28 Aug 2026
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Advanced Upper Gastrointestinal Tract AdenocarcinomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 1,040 participants (actual)
Sponsor and investigators
- Lead sponsor
- Arcus Biosciences, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Gilead Sciences, Taiho Pharmaceutical Co., Ltd.
- Responsible party
- Sponsor
- Investigators
- Medical Director, Study director, Arcus Biosciences
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05568095
- Sponsor's protocol ID
- STAR-221
- Other IDs
- jRCT2051220179, MOH_2023-04-30_012590, CTR20233469, CTR20233470, 2023-507522-16-00, 2023
- Acronym
- STAR-221
- Status last verified
- May 2026
- First submitted
- 3 Oct 2022
- Last updated
- 3 Sep 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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.
Publications
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.
PubMed 40341124