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

NCT07700979 | Not Yet Recruiting Phase 3 DMC FDA Drug

• 1 other identifier: AK104-311
• Study Type: interventional
• Target: 900
• Locations: 4 countries
• Sites: 25

Brief 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.

Conditions

Gastric / Gastroesophageal Junction Adenocarcinoma

Keywords

Gastric/GEJ adenocarcinoma; gastric cancer; cadonilimab; nivolumab; chemotherapy; HER2-negative cancer; Immunotherapy

Outcome Measures

Primary Outcomes (1)

• Overall survival (OS)

  Time from randomization to death from any cause

  Approximately up to 14months

Secondary Outcomes (5)

• Progression-free survival(PFS)

  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

  Approximately up to 18 months

Study Arms (2)

Cadonilimab/placebo+CAPOX

EXPERIMENTAL

Cadonilimab/placebo in combination with oxaliplatin and capecitabine (CAPOX)

Drug: Cadonilimab; Drug: CAPOX regimen; Drug: Placebo

CAPOX±nivolumab/placebo

ACTIVE COMPARATOR

Oxaliplatin and capecitabine with or without nivolumab (CAPOX)

Drug: CAPOX regimen; Drug: Nivolumab; Drug: Placebo

Interventions

Cadonilimab DRUG

Anti-PD-1/ CTLA-4 tetrameric bispecific antibody

Cadonilimab/placebo+CAPOX

CAPOX regimen DRUG

A combination treatment contains oxaliplatin and capecitabine

CAPOX±nivolumab/placebo; Cadonilimab/placebo+CAPOX

Nivolumab DRUG

Anti-PD-1 monoclonal antibody

CAPOX±nivolumab/placebo

Placebo DRUG

Placebo

CAPOX±nivolumab/placebo; Cadonilimab/placebo+CAPOX

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Able to provide written informed consent and can understand and comply with the requirements of the study.
• Histopathologically-confirmed diagnosis of locally advanced unresectable or metastatic G/GEJ adenocarcinoma.
• 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.
• ECOG PS of 0 or 1 within 3 days prior to randomization.
• Age ≥ 18 years at the time of voluntarily signing informed consent.
• Evaluable PD-L1 expression results.
• 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.
• 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.
• Life expectancy ≥3 months.
• 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.
• 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.

You may not qualify if:

• Histopathologically confirmed other pathological types, such as squamous cell carcinoma, sarcoma or undifferentiated carcinoma.
• Known HER2 positive. Be HER2-positive defined as either IHC 3+ or IHC 2+ in combination with ISH+ (or FISH).
• 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.
• Presence of clinically symptomatic pleural effusion, pericardial effusion, or ascites requiring frequent drainage (≥ 1 time/month).
• Clinically significant bleeding symptoms within 28 days before the first dose or a definite tendency to bleed.
• Have a history of ≥ Grade 2 gastrointestinal perforation and/or fistulae (including prior gastric fistula operation) within 6 months prior to randomization.
• 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.

Sponsors & Collaborators

• Akeso: lead

Study Sites (25)

Mayo Clinic

Phoenix, Arizona, 85054, United States

Location

UCLA Health

Los Angeles, California, 90095, United States

Location

Rocky Mountain Cancer Centers

Denver, Colorado, 80218, United States

Location

Yale School of Medicine

New Haven, Connecticut, 06510, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Henry Ford Health

Detroit, Michigan, 48202, United States

Location

Mount Sinai

New York, New York, 10029, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Oregon Health and Science University

Portland, Oregon, 97239, United States

Location

Sarah Cannon Research Institute (SCRI) - Oncology Partners

Nashville, Tennessee, 37203, United States

Location

Baylor Scott & White Health

Dallas, Texas, 75246, United States

Location

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

University of Wisconsin Carbone Cancer Center

Madison, Wisconsin, 53792, United States

Location

Beijing Friendship Hospital, Capital Medical University

Beijing, China

Location

Peking University Cancer Hospital, Gastrointestinal Cancer Center I

Beijing, China

Location

Peking University Cancer Hospital, Gastrointestinal Oncology

Beijing, China

Location

Guangdong Provincial People's Hospital

Guangzhou, China

Location

Zhongshan Hospital Fudan University

Shanghai, China

Location

Universitaetsklinikum Essen

Essen, North Rhine-Westphalia, Germany

Location

University Cancer Center Frankfurt

Frankfurt, Germany

Location

Universitätsmedizin der Johannes Gutenberg-Universität

Mainz, Germany

Location

Univerity Marburg

Marburg, Germany

Location

Pratia MCM Kraków

Krakow, Poland

Location

Pratia Poznań

Poznan, Poland

Location

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

Warsaw, Poland

Location

MeSH Terms

Conditions

Stomach Neoplasms

Interventions

XELOX; Nivolumab

Condition Hierarchy (Ancestors)

Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• 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

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Zhifang Yao, MD

CONTACT

86-0760-89873999; clinicaltrials@akesobio.com

Yelena Janjigian, MD

CONTACT

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 8, 2026
• First Posted: July 14, 2026
• Study Start (Estimated): August 20, 2026
• Primary Completion (Estimated): August 18, 2029
• Study Completion (Estimated): August 18, 2030
• Last Updated: July 14, 2026

Record last verified: 2026-06

Locations

DE (4); US (13); PL (3); CN (5)