Disitamab vedotin plus SOX versus SOX alone as adjuvant treatment for HER2-moderate/high stage III gastric cancer after surgery

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 trial will test whether adding disitamab vedotin to standard SOX chemotherapy helps people with HER2-moderate/high stage III gastric cancer after surgery stay cancer-free longer or live longer.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 124 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: The First Affiliated Hospital with Nanjing Medical University (Academic / other)
• Drugs / interventions: disitamab, chemotherapy
• Locations: 1 site (Nanjing, Jiangsu)
• Trial ID: NCT07474324 on ClinicalTrials.gov

What this trial studies

This randomized phase II trial compares disitamab vedotin (RC48) combined with the SOX chemotherapy regimen versus SOX alone as postoperative adjuvant therapy for patients with HER2-moderate/high stage III gastric or gastroesophageal junction adenocarcinoma who had D2 or wider lymph node dissection and R0 resection. Participants begin adjuvant therapy about four weeks after surgery and receive 6–8 cycles, with imaging every three months to monitor for recurrence and survival follow-up every three months after recurrence. Safety assessments continue from the first dose until 60 days after the last dose or the start of new anti-tumor therapy. Eligible patients must be 18–75 years old, have HER2 IHC 2+ or 3+, ECOG 0–1, adequate organ function, and no prior systemic anti-tumor therapy before surgery.

Who should consider this trial

Good fit: Adults 18–75 with pathologic stage III gastric or gastroesophageal junction adenocarcinoma, HER2 IHC 2+ or 3+, R0 after D2 or wider resection, ECOG 0–1, adequate organ function, and no prior systemic therapy are ideal candidates.

Not a fit: Patients with HER2-negative tumors, prior neoadjuvant systemic therapy, poor organ or bone marrow function, ECOG performance status >1, or inability to attend regular follow-up visits are unlikely to benefit from this trial.

Why it matters

Potential benefit: If successful, adding disitamab vedotin could lower recurrence risk and improve survival for patients with HER2-moderate/high stage III gastric cancer after curative surgery.

How similar studies have performed: Disitamab vedotin has shown promising activity in HER2-positive gastric cancer in earlier-phase and refractory-disease trials, but its use as adjuvant therapy after curative surgery is novel and not yet proven.

Eligibility criteria

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.

Where this trial is running

Nanjing, Jiangsu

• The First Affiliated Hospital with Nanjing Medical University — Nanjing, Jiangsu, China (Recruiting)

Conditions GC/GEJC; adjuvant therapy; Gastric Adenocarcinom; RC48; SOX