A Study of Disitamab Vedotin Combined With Trastuzumab and Tislelizumab Versus Chemotherapy Combined With Trastuzumab With or Without Pembrolizumab in HER2-high Expression Advanced Gastric or Gastroesophageal Junction Adenocarcinoma.

A Randomized Controlled Phase III Study to Evaluate the Combination of Disitamab Vedotin, Trastuzumab, and Tislelizumab Versus Chemotherapy (CAPOX) Combined With Trastuzumab With or Without Pembrolizumab as First-Line Treatment for Advanced Gastric/Gastroesophageal Junction Adenocarcinoma With HER2-high Expression

The purpose of this study is to evaluate the efficacy and safety of Disitamab Vedotin combined with Trastuzumab and Tislelizumab Versus Chemotherapy Combined with Trastuzumab with or without Pembrolizumab as First-Line Treatment for Advanced Gastric/Gastroesophageal Junction Adenocarcinoma with HER2-high Expression.

Study Overview

• Status: Recruiting
• Conditions: Gastric Carcinoma
• Intervention / Treatment: Drug: Disitamab Vedotin; Drug: Tislelizumab; Drug: Trastuzumab; Drug: CAPOX (oxaliplatin/capecitabine); Drug: Pembrolizumab

• Study Type: Interventional
• Enrollment (Estimated): 555
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Hongfang Li; Phone Number: 86+010-65018841; Email: hongfang.li@remegen.com

Study Locations

• China
  • BJ-Beijing
    • Beijing, BJ-Beijing, China, 100021
      • Recruiting
      • Beijing Cancer Hospital
      • Contact: Lin shen; Phone Number: 86+010-88196561; Email: doctorshenlin@sina.cn

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 or metastatic --gastric/gastroesophageal junction adenocarcinoma
• No prior systemic therapy for locally advanced or metastatic gastric cancer; or disease progression or recurrence occurring ≥6 months after completion of neoadjuvant/adjuvant therapy
• HER2-high expression
• At least one assessable lesion according to RECIST v1.1 criteria
• Adequate organ function
• Female subjects of childbearing potential must have a negative blood pregnancy test within 7 days prior to the first treatment, and agree not to breastfeed or donate ova from the signing of the informed consent form until 6 months after the last treatment. Male subjects must agree not to donate sperm from the signing of the informed consent form until 6 months after the last 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
• Severe gastrointestinal dysfunction that may affect drug intake, transport, or absorption
• Bone metastases with a risk of paraplegia
• Past or current interstitial lung disease, or severely impaired lung function
• Other malignancies within 5 years prior to randomization, except for those expected to be cured with treatment
• 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
Experimental: Disitamab Vedotin Combined with Trastuzumab and Tislelizumab; Participants will receive Disitamab Vedotin, Trastuzumab and Tislelizumab until the occurrence of intolerable toxicity, disease progression (investigator-assessed), initiation of new anti-tumor therapy, loss to follow-up, withdrawal of informed consent, or death (whichever occurs first).	Drug: Disitamab Vedotin; Disitamab Vedotin: 2.5 mg/kg, IV, D1, Q2W; Drug: Tislelizumab; Tislelizumab: 200 mg, IV, D1, Q3W; Drug: Trastuzumab; Trastuzumab: Initial dose of 8mg/kg, followed by 6 mg/kg, IV, D1, Q3W;
Active Comparator: Chemotherapy (CAPOX) Combined with Trastuzumab With or Without Pembrolizumab; Participants will receive CAPOX, Trastuzumab and Trastuzumab. Only subjects whose PD-L1 expression is confirmed as CPS ≥1 by the central laboratory will receive pembrolizumab. Treatment will continue until the occurrence of intolerable toxicity, disease progression (investigator-assessed), initiation of new anti-tumor therapy, loss to follow-up, withdrawal of informed consent, or death (whichever occurs first).	Drug: Trastuzumab; Trastuzumab: Initial dose of 8mg/kg, followed by 6 mg/kg, IV, D1, Q3W; Drug: CAPOX (oxaliplatin/capecitabine); Oxaliplatin: 130 mg/m², IV, D1, Q3W; Capecitabine: 1000 mg/m², po, BID, D1-D14, Q3W; Drug: Pembrolizumab; Pembrolizumab: 200mg, IV, D1, Q3W

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-Free Survival (assessed by the BIRC)	Progression-free survival (PFS) is defined as the time from the date of randomization to disease progression per RECIST 1.1 as assessed by Blinded Independent Review Committee (BIRC) or death due to any cause, whichever occurs first.	24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival	Overall survival (OS) refers to the time from the date of randomization to the date of death from any cause.	up to 5 years
Progression-Free Survival (assessed by the investigator)	PFS is defined as the time from randomization to the first documented disease progression per RECIST 1.1 as assessed by investigators or death due to any cause, whichever occurs first.	24 months
Objective Response Rate (assessed by the BIRC and investigators)	ORR is defined as the percentage of subjects who have a Complete Response (CR) or Partial Response (PR) per RECIST 1.1 as assessed by BICR and investigators .	24 months
Disease Control Rate (assessed by the BIRC and investigators)	DCR is defined as the proportion of subjects whose BOR is rated as CR, PR, or stable disease (SD) per RECIST 1.1 as assessed by BICR/ investigators .	24 months
Duration of Response (assessed by the BIRC and investigators)	For participants who demonstrate CR or PR, DOR is defined as the time from first response (CR or PR) to subsequent disease progression or death from any cause, whichever occurs first.	24 months
Patient-Reported Outcomes (EORTC-QLQ-C30)	The EORTC-QLQ-C30 is a 30-item cancer-specific instrument consisting of 5 functional scales (physical, role, emotional, social and cognitive), 9 symptom scales/items (fatigue, nausea/vomiting, general pain, dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties) and a global health status scale. Most items are scored 1 ("not at all") to 4 ("very much") except for the items contributing to the global health status/QoL, which are scored 1 ("very poor") to 7 ("excellent"). All raw domain scores are linearly transformed to a 0-100 scale with higher scores on symptoms indicate a worse health state.	24 months
Patient-Reported Outcomes (EORTCQLQ-STO22)	Quality of life in patients with colorectal cancer is assessed using the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ) STO22. It will be evaluated at Screening and Tumor Assessment Visit. The higher score means the worse quality of life.	24 months
Patient-Reported Outcomes (EQ-5D-5L)	EQ-5D-5L is a standardized instrument for use as a measure of health outcomes consisting of 6 items that cover 5 main domains (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression) and a general visual analog scale for health status.It was developed by the EuroQol Group for use as a generic, preference-based measure of health outcomes. Each dimension comprises 5 levels (no problems, slight problems, moderate problems, severe problems, extreme problems). A unique EQ-5D-5L health state is defined by combining 1 level from each of the 5 dimensions. This questionnaire also records the respondent's self-rated health status on a vertical graduated (0 = the worst health a participant can imagine to 100 = the best health a participant can imagine) visual analogue scale. Responses to the 5 items will also be converted to a weighted health state index (utility score) based on values derived from general population samples.	24 months
Adverse Events	Incidence, severity, and relationship to the investigational product of adverse events (AEs) and serious adverse events (SAEs)	24 months

Collaborators and Investigators

• Sponsor: RemeGen Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Estimated): January 1, 2026
• Primary Completion (Estimated): June 30, 2029
• Study Completion (Estimated): December 31, 2030

Study Registration Dates

• First Submitted: December 3, 2025
• First Submitted That Met QC Criteria: December 23, 2025
• First Posted (Actual): January 2, 2026

Study Record Updates

• Last Update Posted (Actual): January 21, 2026
• Last Update Submitted That Met QC Criteria: January 20, 2026
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases; Stomach Neoplasms; Amino Acids, Peptides, and Proteins; Proteins; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleic Acids, Nucleotides, and Nucleosides; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins; Coordination Complexes; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Nucleosides; Uracil; Pyrimidinones; Deoxyribonucleosides; Fluorouracil; Trastuzumab; Capecitabine; Oxaliplatin; disitamab vedotin; pembrolizumab; tislelizumab
• Other Study ID Numbers: RC48-C040

Drug and device information, study documents

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