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

NCT ID: NCT05008783

Last Updated: 2025-11-19

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 610 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-09-17
• Study Completion Date: 2025-08-01

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

AK104 + Oxaliplatin + Capecitabine

AK104 in combination with Oxaliplatin and Capecitabine

Group Type: EXPERIMENTAL

AK104

Intervention Type: 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)

Placebo + Oxaliplatin + Capecitabine

Placebo in combination with Oxaliplatin and Capecitabine

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: 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)

Interventions

AK104

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)

Intervention Type: DRUG

Placebo

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)

Intervention Type: DRUG

Other Intervention Names

Oxaliplatin; Capecitabine; Oxaliplatin; Capecitabine

Eligibility Criteria

Inclusion Criteria

1. 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.

2. Males or females aged ≥ 18 to ≤ 75 years at the time of signing informed consent.

3. Histopathologically confirmed gastric adenocarcinoma or gastroesophageal junction (GEJ) adenocarcinoma.

4. Unresectable locally advanced or metastatic gastric adenocarcinoma or GEJ adenocarcinoma.

5. 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.

6. 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.

Exclusion Criteria

• Subjects who meet any of the following criteria are not eligible to participate in this study:

1. Subjects with known HER2-positive gastric or GEJ adenocarcinoma.

2. Histopathology or cytology confirmed other pathological types, such as squamous cell carcinoma, sarcoma, or undifferentiated carcinoma.

3. 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.

4. Subjects who received any prior treatments targeting the mechanism of tumor immunity.

5. 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.

6. Active or previously documented inflammatory bowel disease (e.g., Crohn's disease or ulcerative colitis).

7. 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.

8. Known active or untreated brain metastases, meningeal metastases, spinal cord compression, or leptomeningeal disease.

9. Presence of clinically symptomatic pleural effusion, pericardial effusion, or ascites requiring frequent drainage (≥ 1/month).

10. 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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Akeso

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Jiafu Ji, MD

Role: PRINCIPAL_INVESTIGATOR

Peking University Cancer Hospital & Institute

Lin Shen, MD

Role: PRINCIPAL_INVESTIGATOR

Peking University Cancer Hospital & Institute

Locations

Peking University Cancer Hospital

Beijing, Beijing Municipality, China

Fujian Provincial Cancer Hospital

Fuzhou, Fujian, China

Fudan University Cancer Hospital

Shanghai, Shanghai Municipality, China

Zhongshan Hospital, Fudan University

Shanghai, Shanghai Municipality, China

West China Hospital of Sichuan University

Chengdu, Sichuan, China

Yunnan Cancer Hospital

Kunming, Yunnan, China

The First Affiliated Hospital of Zhejiang University Medical College

Hangzhou, Zhejiang, China

Countries

China

References

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.

Reference Type: DERIVED

PMID: 39843940 (View on PubMed)

Other Identifiers

AK104-302

Identifier Type: -

Identifier Source: org_study_id