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

Phase 3

Active, not recruiting

• Conditions: Gastroesophageal Junction Adenocarcinoma; Gastric Adenocarcinoma
• Interventions: Drug: Placebo; Drug: AK104

• Registration Number: NCT05008783
• Lead Sponsor: Akeso

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2021-07-30
• Study First Submitted QC: 2021-08-16
• Study First Posted: 2021-08-17
• Study Start: 2021-09-17
• Status Verified: 2025-03
• Last Update Submitted: 2025-03-06
• Last Update Posted: 2025-03-07
• Primary Completion: 2025-04-18
• Study Completion: 2025-10-18

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 610

Inclusion Criteria

• Subjects must meet all of the following inclusion criteria to be enrolled in the study:

  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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo + Oxaliplatin + Capecitabine	Placebo	Placebo in combination with Oxaliplatin and Capecitabine
AK104 + Oxaliplatin + Capecitabine	AK104	AK104 in combination with Oxaliplatin and Capecitabine

Primary Outcome Measures

Name	Time	Method
Overall Survival (os)	Up to 2 years	OS in the ITT population.

Secondary Outcome Measures

Name	Time	Method
TTR	Up to 2 years	TTR is defined as the time to response base on RECIST v1.1
DoR	Up to 2 years	DoR is defined as the duration from the first documentation of objective response to the first documented disease progression or death due to any cause, whichever occurs first.
AE	From the subject signs the ICF to 30 days (AE) and 90 days (SAE) after the last dose of study treatment or initiation of other anti-tumor therapy, whichever occurs first	Incidence and severity of adverse events (AEs) and serious adverse events (SAEs), and clinically significant abnormal laboratory results.
Observed concentrations of AK104	From first dose of AK104 through the last dose of AK104, about average of 9 months.	The endpoints for assessment of PK of AK104 include serum concentrations of AK104 at different timepoints after AK104 administration
ORR	Up to 2 years	ORR is the proportion of subjects with CR or PR based on RECIST v1.1
DCR	Up to 2 years	DCR is defined as the proportion of subjects with CR, PR, or SD, based on RECIST v1.1
PFS	Up to 2 years	PFS is defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurs first assessed by investigator Per RECIST 1.1
Number of subjects who develop detectable anti-drug antibodies (ADAs)	From first dose of AK104 through 30 days after last dose of AK104	The immunogenicity of AK104 will be assessed by summarizing the number of subjects who develop detectable antidrug antibodies (ADAs).

Trial Locations

Locations (7)

West China Hospital of Sichuan University; 🇨🇳 Chengdu, Sichuan, China

The First Affiliated Hospital of Zhejiang University Medical College; 🇨🇳 Hangzhou, Zhejiang, China

Peking University Cancer Hospital; 🇨🇳 Beijing, Beijing, China

Fudan University Cancer Hospital; 🇨🇳 Shanghai, Shanghai, China

Fujian Provincial Cancer Hospital; 🇨🇳 Fuzhou, Fujian, China

Zhongshan Hospital, Fudan University; 🇨🇳 Shanghai, Shanghai, China

Yunnan Cancer Hospital; 🇨🇳 Kunming, Yunnan, China