Retlirafusp Alfa Injection Plus Chemotherapy Versus Investigator's Choice of Anti-PD-1 Antibody Plus Chemotherapy as First-line Treatment for Advanced Gastric Cancer With Liver Metastases

Retlirafusp Alfa Injection Plus Chemotherapy Versus Investigator's Choice of Anti-PD-1 Antibody Plus Chemotherapy for Previously Untreated, Advanced Gastric or Gastroesophageal Junction Cancer With Liver Metastases: a Randomized, Controlled, Multicenter Phase III Clinical Study

This study is a randomized, controlled, open-label phase III clinical trial, aims to compare the efficacy and safety of Retlirafusp alfa injection plus CAPOX versus the investigator's choice of anti-PD-1 antibody plus CAPOX as first-line treatment in patients with advanced gastric cancer (GC) or gastroesophageal junction cancer (GEJC) with liver metastases

Study Overview

• Status: Not yet recruiting
• Conditions: Gastric Adenocarcinoma and Gastroesophageal Junction Adenocarcinoma
• Intervention / Treatment: Drug: Capecitabine; Drug: Oxaliplatin; Drug: Retlirafusp alfa Injection; Drug: Sintilimab or Tislelizumab (based on investigator's choice)

• Study Type: Interventional
• Enrollment (Estimated): 332
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Lin Shen, Prof.; Phone Number: 01088196088; Email: oncogene@163.com

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• 1. Age ≥ 18 years; 2. Patients with recurrent or previously untreated advanced gastric or gastroesophageal junction cancer with liver metastases, histopathologically confirmed as adenocarcinoma.

  3. No prior systemic therapy (including anti-HER2 therapy) for advanced or metastatic GC/GEJC. Patients who have received prior adjuvant or neoadjuvant therapy are eligible provided that the time from completion of last therapy to first recurrence or disease progression is > 6 months.

  4. Eastern Cooperative Oncology Group (ECOG) performance status of 0-1. 5. At least one evaluable lesion according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.

  6. Adequate organ and bone marrow function. 7. Female subjects of non-childbearing potential are defined as those who are postmenopausal, or have undergone documented hysterectomy and/or bilateral oophorectomy. Male subjects and female subjects of childbearing potential must agree to use at least one medically approved contraceptive method during the study and for 120 days after the last dose of study treatment. A serum pregnancy test must be negative within 3 days prior to the start of study treatment, and subjects must not be breastfeeding.

  8. Voluntarily signed informed consent, and willing and able to comply with scheduled visits, study treatment, laboratory tests, and other study procedures.

Exclusion Criteria:

• 1. Known gastric cancer of squamous cell carcinoma, undifferentiated carcinoma, or other histological types, or adenocarcinoma mixed with other histological types.

  2. Untreated or inadequately treated central nervous system (CNS) metastases, or uncontrolled or symptomatic active CNS metastases.

  3. Diagnosis of any other malignancy within 5 years prior to study entry, except for: skin basal cell carcinoma or squamous cell carcinoma that has been locally treated and documented as cured, superficial bladder cancer, cervical carcinoma in situ, breast ductal carcinoma in situ, papillary thyroid carcinoma, and other early-stage tumors with low risk of recurrence that have undergone curative treatment as judged by the investigator.

  4. Presence of any active, known, or suspected autoimmune disease. 5. Prior treatment with TGF-β inhibitors, anti-PD-1/PD-L1 antibodies, anti-PD-L2 antibodies, anti-CD137 antibodies, CTLA-4 antibodies, or other drugs/antibodies targeting T-cell costimulatory or checkpoint pathways.

  6. Severe, non-healing, or dehiscent wound, or active ulcer, or untreated fracture.

  7. Any other serious physical or mental illness, or laboratory abnormalities that may increase the risk of study participation, interfere with study results, or render the subject unsuitable for the study judged by the investigator.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Retlirafusp alfa Group	Drug: Capecitabine; Capecitabine, Q3W; Drug: Oxaliplatin; Oxaliplatin, Q3W; Drug: Retlirafusp alfa Injection; Retlirafusp alfa injection,1800mg, Q3w
Active Comparator: Investigator's choice of anti-PD-1 antibody Group	Drug: Capecitabine; Capecitabine, Q3W; Drug: Oxaliplatin; Oxaliplatin, Q3W; Drug: Sintilimab or Tislelizumab (based on investigator's choice); Sintilimab or Tislelizumab, Q3w

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Progression-free Survival (PFS) based on investigator assessment according to RECIST 1.1	Up to 2 years

Secondary Outcome Measures

Outcome Measure	Time Frame
Overall survival (OS)	Up to approximately 5 years
Objective response rate (ORR) based on investigator assessment according to RECIST 1.1	Up to 2 years
Disease control rate (DCR) based on investigator assessment according to RECIST 1.1	Up to 2 years
Duration of response (DoR) based on investigator assessment according to RECIST 1.1	Up to 2 years
Adverse events (AEs).	Up to approximately 5 years

Collaborators and Investigators

• Sponsor: Peking University

Study record dates

Study Major Dates

• Study Start (Estimated): June 26, 2026
• Primary Completion (Estimated): December 31, 2028
• Study Completion (Estimated): December 31, 2028

Study Registration Dates

• First Submitted: June 24, 2026
• First Submitted That Met QC Criteria: June 24, 2026
• First Posted (Actual): June 30, 2026

Study Record Updates

• Last Update Posted (Actual): June 30, 2026
• Last Update Submitted That Met QC Criteria: June 24, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleic Acids, Nucleotides, and Nucleosides; Coordination Complexes; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Nucleosides; Uracil; Pyrimidinones; Deoxyribonucleosides; Fluorouracil; Capecitabine; Oxaliplatin; sintilimab; tislelizumab
• Other Study ID Numbers: MA- GC-III-034

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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