A Study of Disitamab Vedotin Combined With Tislelizumab and Chemotherapy Versus Tislelizumab Combined With Chemotherapy in HER2-Low Advanced Gastric or Gastroesophageal Junction Adenocarcinoma

A Phase III, Randomized Trial Comparing RC48 Plus Chemotherapy and Tislelizumab With Tislelizumab Plus Chemotherapy as First-line Treatment in Participants With HER2 Low Advanced Gastric or Gastrioesophageal Junction Adenocarcinoma (RC48-C039)

The purpose of this study is to evaluate the efficacy and safety of **Disitamab Vedotin combined with Tislelizumab and CAPOX versus Tislelizumab combined with CAPOX** as first-line treatment for patients with HER2-low advanced gastric or gastroesophageal junction adenocarcinoma.

Study Overview

• Status: Not yet recruiting
• Conditions: Gastric Carcinoma
• Intervention / Treatment: Biological: Tislelizumab+Oxaliplatin+Capecitabine; Biological: Disitamab Vedotin+Tislelizumab+Oxaliplatin+Capecitabine

• Study Type: Interventional
• Enrollment (Estimated): 616
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: SU Xiaohong Study Director, M.D; Phone Number: +0810-65391479; Email: xiaohong.su@remegen.cn

Study Locations

• China
  • BJ-Beijing
    • Beijing, BJ-Beijing, China, 100021
      • Beijing Cancer Hospital
      • Contact: shen lin shen, PhD; Phone Number: 18018029623

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Voluntarily consent to participate in the study and sign the informed consent form
• Expected survival period >12 weeks
• ECOG Performance Status 0 or 1
• Histologically confirmed unresectable locally advanced, metastatic, or recurrent gastric or gastroesophageal junction adenocarcinoma
• No prior systemic therapy for locally advanced or metastatic gastric cancer
• HER2-low expression
• At least one assessable lesion according to RECIST v1.1 criteria
• Adequate organ function
• For female subjects: They should be surgically sterilized, postmenopausal, or agree to use a medically approved contraceptive method (such as an intrauterine device, contraceptive pill, or condom) during the study treatment period and for 6 months after the end of the study treatment. A blood pregnancy test must be negative within 7 days before the study medication is administered, and they must not be breastfeeding
• For male subjects: They should be surgically sterilized or agree to use a medically approved contraceptive method during the study treatment period and for 6 months after the end of the study treatment
• Able to understand the study requirements and willing to comply with the study and follow-up procedures

Exclusion Criteria:

• Presence of central nervous system (CNS) metastasis and/or carcinomatous meningitis
• Peripheral neuropathy > Grade 1
• Tumor lesions with a tendency to bleed
• Uncontrolled diarrhea
• Bone metastases with a risk of paraplegia
• Past or current interstitial lung disease, or presence of drug-induced pneumonia, radiation pneumonia, or severely impaired lung function
• Other malignancies within 5 years before the first dose, except for those expected to be cured with treatment (e.g., adequately treated thyroid cancer, cervical carcinoma in situ, basal or squamous cell skin cancer, or ductal carcinoma in situ of the breast treated with curative surgery)
• Pregnant or breastfeeding women

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
Active Comparator: Tislelizumab combined with CAPOX	Biological: Tislelizumab+Oxaliplatin+Capecitabine; Tislelizumab: 200 mg, IV, D1, Q3W Oxaliplatin: 130 mg/m², IV, D1, Q3W; Capecitabine: 1000 mg/m², po, BID, D1-D14, Q3W
Experimental: Disitamab Vedotin Combined with Tislelizumab and CAPOX	Biological: Disitamab Vedotin+Tislelizumab+Oxaliplatin+Capecitabine; Disitamab Vedotin: 2.5 mg/kg, IV, D1, Q2W; Tislelizumab: 200 mg, IV, D1, Q3W Oxaliplatin: 100 mg/m², IV, D1, Q3W; Capecitabine: 750 mg/m², po, BID, D1-D14, Q3W

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Progression-Free Survival	24 months

Secondary Outcome Measures

Outcome Measure	Time Frame
Overall Survival	up to 5 years
Objective Response Rate	24 months
Adverse Events	24 months
Duration of Response	24 months
Disease Control Rate	24 months
Patient-Reported Outcomes	24 months

Collaborators and Investigators

• Sponsor: RemeGen Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Estimated): May 15, 2025
• Primary Completion (Estimated): May 15, 2028
• Study Completion (Estimated): May 15, 2030

Study Registration Dates

• First Submitted: April 17, 2025
• First Submitted That Met QC Criteria: April 23, 2025
• First Posted (Actual): April 25, 2025

Study Record Updates

• Last Update Posted (Actual): April 25, 2025
• Last Update Submitted That Met QC Criteria: April 23, 2025
• Last Verified: April 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Neoplasms by Histologic Type; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases; Neoplasms, Glandular and Epithelial; Carcinoma; Stomach Neoplasms; Adenocarcinoma; Antineoplastic Agents, Immunological; Antineoplastic Agents; Immunologic Factors; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antimetabolites, Antineoplastic; Antimetabolites; Immunoconjugates; Capecitabine; Oxaliplatin; Tislelizumab; Disitamab vedotin
• Other Study ID Numbers: RC48-C039

Drug and device information, study documents

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