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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
A 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
Who can join
Ages 18 and older · All sexes
Full eligibility criteria
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.
About the study
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.
What is being tested
- Cadonilimab (drug)
- CAPOX regimen (drug)
- Nivolumab (drug)
- Placebo (drug)
Sponsor: Akeso · Participants: 900 · Started: Sep 24, 2026
Contact the study team
- Zhifang Yao, MD · Phone: 86-0760-89873999
Official record on ClinicalTrials.gov — NCT07700979
Locations in the U.S.
| Arizona | Mayo Clinic, Phoenix (Not yet recruiting) |
| California | UCLA Health, Los Angeles (Not yet recruiting) |
| Colorado | Rocky Mountain Cancer Centers, Denver (Not yet recruiting) |
| Connecticut | Yale School of Medicine, New Haven (Not yet recruiting) |
| Massachusetts | Dana Farber Cancer Institute, Boston (Not yet recruiting) |
| Michigan | Henry Ford Health, Detroit (Not yet recruiting) |
| New York | Memorial Sloan Kettering Cancer Center, New York (Not yet recruiting) Mount Sinai, New York (Not yet recruiting) |
| Oregon | Oregon Health and Science University, Portland (Not yet recruiting) |
| Tennessee | Sarah Cannon Research Institute (SCRI) - Oncology Partners, Nashville (Not yet recruiting) |
| Texas | Baylor Scott & White Health, Dallas (Not yet recruiting) MD Anderson Cancer Center, Houston (Not yet recruiting) |
| Wisconsin | University of Wisconsin Carbone Cancer Center, Madison (Not yet recruiting) |
Conditions
From ClinicalTrials.gov, data retrieved Sep 30, 2026. Each study sets its own eligibility; the study team decides who can join.