A randomized, open, multicenter Phase II study to explore the sequential use of chemotherapy and immunotherapy in postoperative adjuvant therapy for gastric or esophagogastric junction adenocarcinoma or colorectal adenocarcinoma with radical resection of POLE/POLD1 gene mutation or dMMR/MSI-H

Introduction Patients with POLE/POLD1 gene mutation and dMMR/MSI-H are the dominant groups with immune benefit and may benefit from immunotherapy. At present all guidelines recommend observation or chemotherapy based on stage and risk factors for postoperative adjuvant treatment of gastric adenocarcinoma or colorectal cancer. There is no definitive conclusion as to whether immune checkpoint inhibitors or standard chemotherapy is more appropriate.This study aims to explore the optimal postoperative adjuvant treatment mode for locally advanced GC/GEJC or CRC with POLE/POLD1 mutation and dMMR/MSI-H.A simple randomized controlled trial will compare the efficacy of chemotherapy and immunotherapy in eradicating minimal residual disease in patients at high risk of recurrence with positive MRD after surgery. The application of chemotherapy and immunotherapy in postoperative adjuvant therapy in patients who benefit from immunotherapy can reduce the accumulation of chemotherapy side effects caused by the number of unnecessary chemotherapy cycles and, so as to maximize the advantages of immunotherapy . Methods and analysis The patients included in this study are G/GEJ adenocarcinoma undergoing radical gastrectomy with postoperative pathological stage III, or intestinal adenocarcinoma with postoperative pathological stage TanyN + M0 or T4NanyM0 with POLE/POLD1 gene mutation or dMMR/MSI-H, and will be randomly assigned to two groups:Group A receive chemotherapy followed by tislelizumab monotherapy; Group B receive tislelizumab first, followed by chemotherapy. The chemotherapy regimen is XELOX or SOX. Up to 4 cycles of chemotherapy or immunotherapy will be performed.The 1-year disease-free survival rate, 1-year MRD-negative survival rate, OS, PFS, safety,the dynamic change of MRD and other indicators of the two groups will be evaluated.This study will provide clinical guidance for adjuvant therapy in dMMR/MSI-H or POLE/POLD1 gene-mutated GC/GEJC and CRC case. Trial registration number NCT06118658