Disitamab Vedotin Combined With SOX Regimen Versus SOX Alone as Adjuvant Therapy for HER2-Moderate/High Expressing Stage Ⅲ Gastric Cancer: A Prospective, Multicenter, Randomized, Phase Ⅱ Clinical Trial

This is a prospective, multicenter, randomized, phase II clinical trial intended to enroll patients with HER2-moderate/high-expressing, pathologically staged stage III gastric cancer who have undergone D2 or more extensive surgery. The study aims to evaluate the preliminary efficacy and safety of disitamab vedotin combined with the SOX regimen versus SOX alone as post-operative adjuvant therapy.

Study Overview

• Status: Recruiting
• Conditions: GC/GEJC
• Intervention / Treatment: Drug: RC48; Drug: SOX Chemotherapy; Drug: SOX(normal)

Detailed Description

After providing informed consent and meeting all eligibility criteria, participants will begin adjuvant therapy with disitamab vedotin plus chemotherapy (SOX) approximately four weeks after surgery, continuing for 6-8 cycles. Post-operative imaging assessments will be performed every three months until disease recurrence. Following recurrence, survival follow-up will be conducted every three months. Safety visits will continue from first drug administration until 60 days after the last dose or until initiation of new anti-tumor therapy.

• Study Type: Interventional
• Enrollment (Estimated): 124
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Jiangsu
    • Nanjing, Jiangsu, China, 210000
      • Recruiting
      • The First Affiliated Hospital with Nanjing Medical University
      • Contact: Hao Xu; Phone Number: 13851530117; Email: hxu@njmu.edu.cn

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Aged between 18 and 75 years.
• Have undergone radical resection with D2 or wider lymph node dissection and achieved R0 resection status.
• No prior systemic anti-tumor treatment (i.e., neoadjuvant therapy) before surgery.
• Histopathologically confirmed gastric adenocarcinoma.
• Pathological stage III gastric and gastroesophageal junction adenocarcinoma patients (according to the 8th edition of the American Joint Committee on Cancer [AJCC] staging system).
• HER2 moderate-to-high expression (IHC 3+ or 2+).
• Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 or 1.
• Expected survival time ≥ 3 months.
• Able to understand the study protocol, voluntarily participate in the study, and provide written informed consent;
• Good compliance and able to cooperate with the treatment regimen specified in this study;
• Possesses complete imaging and pathological clinical data;
• Adequate organ and bone-marrow function.

Exclusion Criteria:

• Primary stage III gastric or gastroesophageal-junction adenocarcinoma not histologically or cytologically confirmed;
• Unable to receive disitamab vedotin or SOX chemotherapy;
• Unable to comply with the required follow-up schedule;
• Unable to accept the treatment regimen specified in this protocol;
• Unable or unwilling to undergo mandated response assessments (e.g., CT imaging);
• Active autoimmune disease;
• History of psychoactive-substance abuse that cannot be discontinued, or any severe/uncontrolled psychiatric disorder, or any severe/uncontrolled systemic disease;
• Any concomitant condition that, in the investigator's opinion, poses significant risk to the subject or could compromise study completion;
• Other malignancies within 5 years before screening, except adequately treated cancers considered cured (e.g., thyroid cancer, cervical carcinoma in situ, basal/squamous-cell skin cancer, or ductal carcinoma in situ of the breast treated with curative surgery);
• Lactating women;
• Prior neoadjuvant therapy or intra-operative intraperitoneal chemotherapy.

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: SOX; Patients will receive 6 to 8 cycles of treatment with SOX	Drug: SOX(normal); S-1: 40 mg/m², oral administration (p.o.), twice daily (b.i.d.), on Days 1 to 14; repeated every 21 days. Oxaliplatin: 130 mg/m², intravenous infusion (i.v.gtt.), on Day 1; repeated every 21 days.
Experimental: RC48+SOX; Patients will first receive 6 to 8 cycles of treatment with RC48 + SOX	Drug: RC48; RC48 2.5mg/kg iv. ,q3w; Drug: SOX Chemotherapy; S-1: 40-60 mg/m², oral administration (p.o.), twice daily (b.i.d.), on Days 1 to 14; repeated every 21 days. Oxaliplatin: 100 mg/m², intravenous infusion (i.v.gtt.), on Day 1; repeated every 21 days.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
3-year-DFS rate	The 3-year disease-free survival (DFS) rate is defined as the proportion of participants who remain free of any of the following events for at least three years from the date of randomization: tumor recurrence, new primary tumor, or death from any cause. Patients who undergo curative-intent surgery and experience none of these events are considered disease-free.	3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival (OS)	Defined from date of recruit to date of first documentation of death from any cause or censored at the date of the last follow-up.	5 years
Incidence rate of adverse events (AEs)	Analysis of adverse events (AEs) are based on treatment-related AEs (trAEs) and immune-related AEs (irAEs), and all-grade AEs and grade 3-4 AEs. AEs are evaluated by investigators according to the Common Terminology Criteria for Adverse Events, version 5.0	3 years
Disease-Free Survival (DFS)	Defined from the date of completion of curative-intent treatment (e.g., surgery, adjuvant chemotherapy) to the date of first documentation of disease recurrence (e.g., tumor relapse, metastasis) or death from any cause, whichever occurs first.	3 years
2-year-OS rate	The 2-year overall survival (OS) rate is defined as the proportion of participants who remain alive for at least two years from the date of randomization, regardless of whether disease recurrence or progression has occurred.	2 years
3-year OS rate	The 3-year overall survival (OS) rate is defined as the proportion of participants who remain alive for at least two years from the date of randomization, regardless of whether disease recurrence or progression has occurred.	3 years

Collaborators and Investigators

• Sponsor: The First Affiliated Hospital with Nanjing Medical University

Study record dates

Study Major Dates

• Study Start (Estimated): March 15, 2026
• Primary Completion (Estimated): December 31, 2028
• Study Completion (Estimated): December 31, 2030

Study Registration Dates

• First Submitted: March 11, 2026
• First Submitted That Met QC Criteria: March 11, 2026
• First Posted (Actual): March 16, 2026

Study Record Updates

• Last Update Posted (Actual): March 16, 2026
• Last Update Submitted That Met QC Criteria: March 11, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Keywords: adjuvant therapy; SOX; RC48; Gastric Adenocarcinom
• Other Study ID Numbers: RCVDTYPEC174

Drug and device information, study documents

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