Phase II Study of Trastuzumab Rezetecan Combined With Retlirafusp Alfa With or Without CAPOX as Perioperative Therapy for Resectable Locally Advanced Gastric/Gastroesophageal Junction Adenocarcinoma

This two‐stage, multicenter, randomized open‐label phase II trial enrolls untreatedresectable stage II‐III gastric/gastroesophageal junction adenocarcinoma patients withany HER2 expression. Stage 1 is a safety lead‐in cohort of 6 patients receivingTrastuzumab Rezetecan(SHR‐A1811)+Retlirafusp alfa(SHR‐1701) plus CAPOX to assessdose‐limiting toxicity (DLT) within 21 days after initial dosing. If safety risk isacceptable, stage 2 will randomize 74 eligible patients 1:1 into two parallel cohortsstratified by HER2 status. Cohort1 receives perioperative TrastuzumabRezetecan(SHR‐A1811)+Retlirafusp alfa(SHR‐1701)+CAPOX; Cohort2 receives dualtargeted‐immunotherapy without chemotherapy (Trastuzumab Rezetecan+Retlirafusp alfa). Allpatients undergo D2 radical gastrectomy after neoadjuvant therapy, followed by adjuvanttreatment and Retlirafusp alfa(SHR‐1701) maintenance up to maximum 17 total cycles. Theprimary endpoint is pCR rate evaluated by CAP pathological criteria. Secondary endpointsinclude R0 resection rate, EFS, DFS, OS and perioperative/surgical/systemic safetyprofiles. Biomarker exploratory analysis will be performed to evaluate the correlationbetween PD‐L1, MSI, TMB and clinical efficacy.