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NCT07700979PHASE3Recruiting

Phase 3 Study of Cadonilimab Combined With Chemotherapy vs Chemotherapy in Combination With or Without Nivolumab for the 1L Treatment of Participants With HER2-negative, Previously Untreated, Unresectable or Metastatic Gastric/GEJ Adenocarcinoma

Akeso

Start Date

9/24/2026

Completion Date

8/18/2030

Summary

The goal of this randomized, double-blind, multi-regional phase 3 study of cadonilimab combined with chemotherapy versus chemotherapy in combination with or without nivolumab for the first-line treatment of participants with HER2-negative, previously untreated, unresectable or metastatic gastric or gastroesophageal junction adenocarcinoma trial is to compare OS between cadonilimab combined with chemotherapy and chemotherapy in combination with or without nivolumab in the ITT population.

Eligibility Criteria

Age Range: 18 years to No maximum

Inclusion Criteria: 1. Able to provide written informed consent and can understand and comply with the requirements of the study. 2. Histopathologically-confirmed diagnosis of locally advanced unresectable or metastatic G/GEJ adenocarcinoma. 3. No prior systemic therapy for locally advanced unresectable or metastatic G/GEJ adenocarcinoma. NOTE: For participants who have received prior neoadjuvant/adjuvant therapy for curative intent, the time between disease progression and last treatment should be at least 6 months. 4. ECOG PS of 0 or 1 within 3 days prior to randomization. 5. Age ≥ 18 years at the time of voluntarily signing informed consent. 6. Evaluable PD-L1 expression results. 7. Participants must have at least one measurable lesion per RECIST v1.1 as assessed by investigator assessment. Lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions. 8. Adequate organ function as indicated by the following laboratory values. Specimens must be collected within 7 days prior to the first dose of study treatment. 9. Life expectancy ≥3 months. 10. Women of childbearing potential (WOCBP) must have a negative serum pregnancy test within 7 days prior to the first dose and agree to use effective contraception during treatment, and for at least 150 days after the last dose of cadonilimab/nivolumab, 270 days after the last dose of oxaliplatin, and 180 days after the last dose of capecitabine. 11. Non-sterile males must agree to use effective contraception during treatment and for at least 120 days following the last dose of cadonilimab/nivolumab/capecitabine and 180 days after the last dose of oxaliplatin. Exclusion Criteria: 1. Histopathologically confirmed other pathological types, such as squamous cell carcinoma, sarcoma or undifferentiated carcinoma. 2. Known HER2 positive. Be HER2-positive defined as either IHC 3+ or IHC 2+ in combination with ISH+ (or FISH). 3. Participants with active central nervous system (CNS) metastases and/or carcinomatous meningitis. Participants with previously treated brain metastases may participate provided they are radiologically stable (i.e., without evidence of progression) for at least 4 weeks by repeat imaging (note that the repeat imaging should be performed during study screening), clinically stable and without requirement of steroid treatment for at least 14 days prior to first dose of study intervention. 4. Presence of clinically symptomatic pleural effusion, pericardial effusion, or ascites requiring frequent drainage (≥ 1 time/month). 5. Clinically significant bleeding symptoms within 28 days before the first dose or a definite tendency to bleed. 6. Have a history of ≥ Grade 2 gastrointestinal perforation and/or fistulae (including prior gastric fistula operation) within 6 months prior to randomization. 7. Participants who, in the opinion of the investigator, have symptoms or signs suggestive of clinically unacceptable deterioration of the primary disease at the time of screening.

Interventions

DRUG

Cadonilimab

DRUG

CAPOX regimen

DRUG

Nivolumab

DRUG

Placebo

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Conditions

Gastric / Gastroesophageal Junction Adenocarcinoma

Locations

Mayo Clinic

Phoenix, Arizona 85054

United States

UCLA Health

Los Angeles, California 90095

United States

Rocky Mountain Cancer Centers

Denver, Colorado 80218

United States

Yale School of Medicine

New Haven, Connecticut 06510

United States

Dana Farber Cancer Institute

Boston, Massachusetts 02215

United States

Henry Ford Health

Detroit, Michigan 48202

United States

Mount Sinai

New York, New York 10029

United States

Memorial Sloan Kettering Cancer Center

New York, New York 10065

United States

Oregon Health and Science University

Portland, Oregon 97239

United States

Sarah Cannon Research Institute (SCRI) - Oncology Partners

Nashville, Tennessee 37203

United States

Baylor Scott & White Health

Dallas, Texas 75246

United States

MD Anderson Cancer Center

Houston, Texas 77030

United States

University of Wisconsin Carbone Cancer Center

Madison, Wisconsin 53792

United States

Beijing Friendship Hospital, Capital Medical University

Beijing,

China

Peking University Cancer Hospital, Gastrointestinal Cancer Center I

Beijing,

China

Peking University Cancer Hospital, Gastrointestinal Oncology

Beijing,

China

Guangdong Provincial People's Hospital

Guangzhou,

China

Zhongshan Hospital Fudan University

Shanghai,

China

Universitaetsklinikum Essen

Essen, North Rhine-Westphalia

Germany

University Cancer Center Frankfurt

Frankfurt,

Germany

Universitätsmedizin der Johannes Gutenberg-Universität

Mainz,

Germany

Univerity Marburg

Marburg,

Germany

Pratia MCM Kraków

Krakow,

Poland

Pratia Poznań

Poznan,

Poland

Narodowy Instytut Onkologii-im. Marii Sklodowskiej Curie Panstwowy Instytut Badawczy - w Warszawie

Warsaw,

Poland