This two-stage, multicenter, randomized open-label phase II trial enrolls untreated resectable stage II-III gastric/gastroesophageal junction adenocarcinoma patients with any HER2 expression. Stage 1 is a safety lead-in cohort of 6 patients receiving Trastuzumab Rezetecan(SHR-A1811)+Retlirafusp alfa(SHR-1701) plus CAPOX to assess dose-limiting toxicity (DLT) within 21 days after initial dosing. If safety risk is acceptable, stage 2 will randomize 74 eligible patients 1:1 into two parallel cohorts stratified by HER2 status. Cohort1 receives perioperative Trastuzumab Rezetecan(SHR-A1811)+Retlirafusp alfa(SHR-1701)+CAPOX; Cohort2 receives dual targeted-immunotherapy without chemotherapy (Trastuzumab Rezetecan+Retlirafusp alfa). All patients undergo D2 radical gastrectomy after neoadjuvant therapy, followed by adjuvant treatment and Retlirafusp alfa(SHR-1701) maintenance up to maximum 17 total cycles. The primary endpoint is pCR rate evaluated by CAP pathological criteria. Secondary endpoints include R0 resection rate, EFS, DFS, OS and perioperative/surgical/systemic safety profiles. Biomarker exploratory analysis will be performed to evaluate the correlation between PD-L1, MSI, TMB and clinical efficacy.
Voluntarily sign written informed consent before any study-related procedures
Age ≥18 and ≤75 years old
Histopathologically confirmed gastric or gastroesophageal junction adenocarcinoma
AJCC 8th edition stage II-III resectable disease (cT1-2N+M0, T3-4aNanyM0); negative peritoneal cytology (CY0) confirmed by pre-study laparoscopy
Siewert type I GEJ tumor or Siewert II tumor requiring cervicothoracic surgical approach
Confirmed peritoneal metastasis, positive peritoneal cytology (CY1), or AJCC T4b disease
Tumor unresectable or absolute contraindication to radical gastrectomy
History of other malignant tumor within past 5 years (excluding cured basal cell skin carcinoma, cervical/breast carcinoma in situ)
Parallel
Trastuzumab Rezetecan + Retlirafusp alfa + CAPOX
Drug1. Drug: Trastuzumab Rezetecan Description: IV infusion Q3W; Cycle 1 loading dose 6.4 mg/kg, subsequent cycles 4.8 mg/kg; administered for 3 neoadjuvant cycles and 3 adjuvant cycles 2. Drug: Retlirafusp alfa Description: IV infusion 1800 mg Q3W; 3 neoadjuvant, 3 adjuvant cycles, then single-agent maintenance up to total 17 cycles 3. Drug: Oxaliplatin Description: 60 mg/m² IV Q3W, only 3 neoadjuvant cycles 4. Drug: Capecitabine Description: 750 mg/m² oral twice daily, 2 weeks on / 1 week off; 3 neoadjuvant + 3 adjuvant cycles 5. Procedure: Radical D2 Gastrectomy Description: R0 curative resection performed 3-6 weeks post final neoadjuvant dose
Trastuzumab Rezetecan + Retlirafusp Alfa
Drug1. Drug: Trastuzumab Rezetecan Description: IV infusion Q3W; Cycle 1 loading dose 6.4 mg/kg, subsequent cycles 4.8 mg/kg; administered for 3 neoadjuvant cycles and 3 adjuvant cycles 2. Drug: Retlirafusp alfa Description: IV infusion 1800 mg Q3W; 3 neoadjuvant, 3 adjuvant cycles, then single-agent maintenance up to total 17 cycles 3. Procedure: Radical D2 Gastrectomy Description: R0 curative resection performed 3-6 weeks post final neoadjuvant dose
Pathological Complete Response (pCR)
Proportion of subjects achieving CAP Tumor Regression Grade 0 (TRG0), defined as no viable malignant cells detected in primary gastric tumor and all regional lymph nodes after radical D2 gastrectomy
R0 Resection Rate
The proportion of subjects who achieve R0 resection confirmed by postoperative surgical pathology.
Event-Free Survival (EFS)
EFS is the time from date of randomization until the date of disease progression or death.(assessed by the investigator per RECIST v1.1 criteria)
Overall Survival (OS)
Overall survival is length of time from randomization until the date of death due to any cause.
Incidence, severity and causality of TEAEs, SAEs graded by NCI-CTCAE 6.0.
Assessment of safety
Click on the lead sponsor to view all of their trials.
This trial is not recruiting at the moment. You can still explore other options:
