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 (G/GEJ)

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

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Gastric / Gastroesophageal Junction Adenocarcinoma
• Intervention / Treatment: Drug: Placebo; Drug: Cadonilimab; Drug: CAPOX regimen; Drug: Nivolumab

• Study Type: Interventional
• Enrollment (Estimated): 900
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Zhifang Yao, MD; Phone Number: 86-0760-89873999; Email: clinicaltrials@akesobio.com
• Study Contact Backup: Name: Yelena Janjigian, MD

Study Locations

• China
  • Beijing, China
    • Beijing Friendship Hospital, Capital Medical University
    • Contact: Wei Deng, MD
  • Beijing, China
    • Peking University Cancer Hospital, Gastrointestinal Cancer Center I
    • Contact: Jiafu Ji, MD
  • Beijing, China
    • Peking University Cancer Hospital, Gastrointestinal Oncology
    • Contact: Lin Shen, MD
  • Guangzhou, China
    • Guangdong Provincial People's Hospital
    • Contact: Jian Xiao, MD
  • Shanghai, China
    • Zhongshan Hospital Fudan University
    • Contact: Xuefei Wang, MD
• Germany
  • Frankfurt, Germany
    • University Cancer Center Frankfurt
    • Contact: Thorsten O Goetze, MD
  • Mainz, Germany
    • Universitätsmedizin der Johannes Gutenberg-Universität
    • Contact: Markus Mohler, MD
  • Marburg, Germany
    • Univerity Marburg
  • North Rhine-Westphalia
    • Essen, North Rhine-Westphalia, Germany
      • Universitaetsklinikum Essen
      • Contact: Isabel Virchow, MD
• Poland
  • Krakow, Poland
    • Pratia MCM Krakow
  • Poznan, Poland
    • Pratia Poznań
    • Contact: Piotr Tomczak, MD
  • Warsaw, Poland
    • Narodowy Instytut Onkologii-im. Marii Sklodowskiej Curie Panstwowy Instytut Badawczy - w Warszawie
    • Contact: Lucjan S Wyrwicz, MD
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85054
      • Mayo Clinic
      • Contact: Ashish Chintakuntlawar,
  • California
    • Los Angeles, California, United States, 90095
      • UCLA Health
      • Contact: Randy Hecht, MD
  • Colorado
    • Denver, Colorado, United States, 80218
      • Rocky Mountain Cancer Centers
      • Contact: Allen L Cohn, MD
  • Connecticut
    • New Haven, Connecticut, United States, 06510
      • Yale School of Medicine
      • Contact: Raghav Sundar, MD
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Dana Farber Cancer Institute
  • Michigan
    • Detroit, Michigan, United States, 48202
      • Henry Ford Health
      • Contact: Zaid AI-Saheli, MD
  • New York
    • New York, New York, United States, 10065
      • Memorial Sloan Kettering Cancer Center
    • New York, New York, United States, 10029
      • Mount Sinai
      • Contact: Deirdre Cohen, MD
  • Oregon
    • Portland, Oregon, United States, 97239
      • Oregon Health and Science University
      • Contact: Emerson Chen, MD
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Sarah Cannon Research Institute (SCRI) - Oncology Partners
      • Contact: David R Spigel, MD
  • Texas
    • Dallas, Texas, United States, 75246
      • Baylor Scott & White Health
    • Houston, Texas, United States, 77030
      • MD Anderson Cancer Center
      • Contact: Jaffer A. Ajani,, MD
  • Wisconsin
    • Madison, Wisconsin, United States, 53792
      • University of Wisconsin Carbone Cancer Center
      • Contact: Nataliya Uboha, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cadonilimab/placebo+CAPOX; Cadonilimab/placebo in combination with oxaliplatin and capecitabine (CAPOX)	Drug: Placebo; Placebo; Drug: Cadonilimab; Anti-PD-1/ CTLA-4 tetrameric bispecific antibody; Drug: CAPOX regimen; A combination treatment contains oxaliplatin and capecitabine
Active Comparator: CAPOX±nivolumab/placebo; Oxaliplatin and capecitabine with or without nivolumab (CAPOX)	Drug: Placebo; Placebo; Drug: CAPOX regimen; A combination treatment contains oxaliplatin and capecitabine; Drug: Nivolumab; Anti-PD-1 monoclonal antibody

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival (OS)	Time from randomization to death from any cause	Approximately up to 14months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free survival(PFS)	Time from the date of randomization to the date of progressive disease or death from any cause, whichever occurs first.	Approximately up to 8 months
Objective response rate (ORR)		Approximately up to 8 months
Disease control rate (DCR)		Approximately up to 8 months
Duration of response (DoR)		Approximately up to 8 months
Safety assessment	Incidence and severity of adverse events (AEs) and clinically significant abnormal laboratory test results	Approximately up to 18 months

Collaborators and Investigators

• Sponsor: Akeso
• Investigators: Principal Investigator: Jiafu Ji, MD, Peking University Cancer Hospital, Beijing, Beijing 100142, China; Principal Investigator: Lin Shen, MD, Peking University Cancer Hospital, Beijing, Beijing 100142, China; Principal Investigator: Markus Mohler, MD, Johannes Gutenberg University Clinic, Germany

Study record dates

Study Major Dates

• Study Start (Estimated): August 20, 2026
• Primary Completion (Estimated): August 18, 2029
• Study Completion (Estimated): August 18, 2030

Study Registration Dates

• First Submitted: July 8, 2026
• First Submitted That Met QC Criteria: July 8, 2026
• First Posted (Actual): July 14, 2026

Study Record Updates

• Last Update Posted (Actual): July 14, 2026
• Last Update Submitted That Met QC Criteria: July 8, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: chemotherapy; Immunotherapy; gastric cancer; nivolumab; cadonilimab; Gastric/GEJ adenocarcinoma; HER2-negative cancer
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases; Stomach Neoplasms; Amino Acids, Peptides, and Proteins; Proteins; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins; Nivolumab; XELOX
• Other Study ID Numbers: AK104-311

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No