This is a phase II open-label study to evaluate the efficacy and safety of zanidatamab combined with chemotherapy as neoadjuvant/conversion therapy in patients with HER2-positive (IHC 3+ or IHC 2+) locally advanced or metastatic gastric/gastroesophageal junction adenocarcinoma. The study consists of two cohorts: a neoadjuvant cohort (Simon's two-stage design, n=46) for treatment-naive stage III locally advanced disease, and an exploratory conversion cohort for oligometastatic disease. Patients receive zanidatamab (30 mg/kg Q3W) plus oxaliplatin-based chemotherapy, with or without PD-1 inhibitor (tislelizumab or sintilimab). The primary endpoint is pathological complete response (pCR).
Willing and able to provide written informed consent (ICF).
Histologically and radiologically (CT/MRI) confirmed gastric or gastroesophageal junction adenocarcinoma.
Neoadjuvant cohort: Clinical stage III (cT3-4aN+M0) or locally advanced unresectable (cT4bNany M0) assessed by MDT as not amenable to R0 resection, or technically resectable but with high-risk factors (e.g., bulky nodal fusion, invasion of critical structures).
Conversion cohort: Not amenable to direct surgery (e.g., invasion of adjacent organs or vessels) or with distant metastases, including liver metastases (C-GCLM type I and II), confirmed retroperitoneal lymph node metastases, or other single-organ metastases.
Synchronous or metachronous malignancies of other organs, or recurrent disease.
Prior systemic therapy for gastric cancer (neoadjuvant cohort).
History of malignancy within 5 years before screening, except those with > 90% 5-year overall survival.
Significant cardiopulmonary dysfunction.
Zhifeng Zhao, PhD
Lead sponsor
Xijing Hospital of Digestive Diseases
Sponsor institution