A Study of AK104 in the First-line Treatment of Locally Advanced Unresectable or Metastatic G/GEJ Adenocarcinoma

NCT05008783 | Completed Phase 3

• 1 other identifier: AK104-302
• Study Type: interventional
• Target: 610
• Locations: 1 country
• Sites: 7

Brief Summary

A randomized, Double-blind, Multicenter, phase III Clinical Study of Comparing the Efficacy and Safety of AK104 Plus Oxaliplatin and Capecitabine (XELOX) Versus Placebo Plus XELOX as First-line Treatment for locally advanced Unresectable or Metastatic Gastric Adenocarcinoma or Gastroesophageal Junction Adenocarcinoma.

Conditions

Gastric Adenocarcinoma; Gastroesophageal Junction Adenocarcinoma

Outcome Measures

Primary Outcomes (1)

• Overall Survival (os)

  OS in the ITT population.

  Up to 2 years

Secondary Outcomes (8)

• ORR

  Up to 2 years

• DCR

  Up to 2 years

• DoR

  Up to 2 years

• TTR

  Up to 2 years

• PFS

  Up to 2 years

Study Arms (2)

AK104 + Oxaliplatin + Capecitabine

EXPERIMENTAL

AK104 in combination with Oxaliplatin and Capecitabine

Drug: AK104

Placebo + Oxaliplatin + Capecitabine

PLACEBO COMPARATOR

Placebo in combination with Oxaliplatin and Capecitabine

Drug: Placebo

Interventions

AK104 DRUG

AK104 (administered on Day 1 of each cycle, Q3W)+Oxaliplatin (130 mg/m2 intravenous infusion for 2-6 hours on Day 1, Q3W,up to 6 cycles)+ Capecitabine(1000 mg/m2, p.o., Bid, Q3W,up to 6 cycles) . Afterward, AK104 will be used for maintenance treatment (administered on Day 1 of each cycle, Q3W)

Also known as: Oxaliplatin, Capecitabine

AK104 + Oxaliplatin + Capecitabine

Placebo DRUG

Placebo (administered on Day 1 of each cycle, Q3W)+Oxaliplatin (130 mg/m2 intravenous infusion for 2-6 hours on Day 1, Q3W,up to 6 cycles)+ Capecitabine(1000 mg/m2, p.o., Bid, Q3W,up to 6 cycles) . Afterward,Placebo will be used for maintenance treatment (administered on Day 1 of each cycle, Q3W)

Also known as: Oxaliplatin, Capecitabine

Placebo + Oxaliplatin + Capecitabine

Eligibility Criteria

• Age: 18 Years - 75 Years
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Ability to understand and voluntarily sign a written informed consent form (ICF), which must be signed before the specified study procedures required for the study are performed.
• Males or females aged ≥ 18 to ≤ 75 years at the time of signing informed consent.
• Histopathologically confirmed gastric adenocarcinoma or gastroesophageal junction (GEJ) adenocarcinoma.
• Unresectable locally advanced or metastatic gastric adenocarcinoma or GEJ adenocarcinoma.
• Subjects have not received prior systemic therapy for locally advanced or metastatic gastric adenocarcinoma or adenocarcinoma of the gastroesophageal junction. For subjects who have received prior neoadjuvant/adjuvant chemotherapy or chemoradiotherapy for curative intent, the time between disease progression and last treatment should be at least 6 months.
• Subjects have at least one measurable tumor lesion per RECIST v1.1; lesions that received radiotherapy are not selected as target lesions, unless the lesion is the only measurable lesion and has unequivocal progression as judged by imaging, it can be considered as a target lesion.

You may not qualify if:

• Subjects who meet any of the following criteria are not eligible to participate in this study:
• Subjects with known HER2-positive gastric or GEJ adenocarcinoma.
• Histopathology or cytology confirmed other pathological types, such as squamous cell carcinoma, sarcoma, or undifferentiated carcinoma.
• Subjects who received palliative local therapy for non-target lesions within 2 weeks prior to the first dose; systemic nonspecific immunomodulatory therapy (e.g., interleukin, interferon, thymosin, etc.) within 2 weeks prior to the first dose; and Chinese herbal medicine or traditional Chinese medicinal products with anti-tumor indications within 2 weeks prior to the first dose.
• Subjects who received any prior treatments targeting the mechanism of tumor immunity.
• Medical history of gastrointestinal perforation or gastrointestinal fistula within 6 months prior to the first dose. If the perforation or fistula has been treated with resection or repair and the disease has recovered or resolved as judged by the Investigator, enrollment may be allowed.
• Active or previously documented inflammatory bowel disease (e.g., Crohn's disease or ulcerative colitis).
• Active malignancies within the past 3 years, with the exception of tumors in this study and cured local tumors, such as basal cell carcinoma of skin, squamous cell carcinoma of skin, superficial bladder cancer, carcinoma in situ of cervix, carcinoma in situ of breast, localized prostate cancer, etc.
• Known active or untreated brain metastases, meningeal metastases, spinal cord compression, or leptomeningeal disease.
• Presence of clinically symptomatic pleural effusion, pericardial effusion, or ascites requiring frequent drainage (≥ 1/month).
• Active autoimmune disease requiring systemic treatment within 2 years prior to the start of study treatment, or autoimmune diseases that may relapse or require scheduled treatment as judged by the Investigator.

Sponsors & Collaborators

• Akeso: lead

Study Sites (7)

Peking University Cancer Hospital

Beijing, Beijing Municipality, 100143, China

Location

Fujian Provincial Cancer Hospital

Fuzhou, Fujian, 350014, China

Location

Fudan University Cancer Hospital

Shanghai, Shanghai Municipality, 200032, China

Location

Zhongshan Hospital, Fudan University

Shanghai, Shanghai Municipality, 20032, China

Location

West China Hospital of Sichuan University

Chengdu, Sichuan, 610044, China

Location

Yunnan Cancer Hospital

Kunming, Yunnan, 650118, China

Location

The First Affiliated Hospital of Zhejiang University Medical College

Hangzhou, Zhejiang, 310003, China

Location

Related Publications (1)

• Shen L, Zhang Y, Li Z, Zhang X, Gao X, Liu B, Wang Y, Ba Y, Li N, Zhang R, Zhang J, Chen Y, Chen J, Huang M, Fu Y, Liu M, Liu Z, Zhao J, Li W, Wei J, Li C, Xu N, Guo Z, Cao B, Liu L, Nie P, Wan L, Sheng L, Liu Z, He Y, Gu K, Wu G, Wang W, Zhang F, Qiu W, Guo J, Ying J, Pan H, Xu H, Yuan Y, Bai Y, Wang Z, Xu J, Zhao X, Liu H, Zhang X, Dai W, Xu H, Liu M, Xie L, Tang Y, Jin J, Qu X, Fang X, Huang M, Chen H, Zheng Z, Wang Y, Wang D, Li X, Yu G, Liu H, Zhou Y, Zhong D, Zeng S, Kang M, Wang M, Gao Y, Li W, Wang Z, Zhang M, Zhang J, Li Q, Sun S, Zang A, Lin L, Xie M, Zhuang Z, Zhang T, Yao Z, Lu D, Liu W, Hu M, Wang ZM, Li B, Xia M, Zhang J, Ying X, Pardoll DM, Ji J. First-line cadonilimab plus chemotherapy in HER2-negative advanced gastric or gastroesophageal junction adenocarcinoma: a randomized, double-blind, phase 3 trial. Nat Med. 2025 Apr;31(4):1163-1170. doi: 10.1038/s41591-024-03450-4. Epub 2025 Jan 22.

  PMID: 39843940 DERIVED

MeSH Terms

Interventions

Oxaliplatin; Capecitabine

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Study Officials

• Jiafu Ji, MD

  Peking University Cancer Hospital & Institute

  PRINCIPAL INVESTIGATOR

• Lin Shen, MD

  Peking University Cancer Hospital & Institute

  PRINCIPAL INVESTIGATOR

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 30, 2021
• First Posted: August 17, 2021
• Study Start: September 17, 2021
• Primary Completion: December 6, 2024
• Study Completion: August 1, 2025
• Last Updated: November 19, 2025

Record last verified: 2025-11

Locations

CN (7)