mFOLFOX6 + Bevacizumab + PD-1 Monoclonal Antibody Vs. mFOLFOX6 in Locally Advanced pMMR/MSS CRC

This clinical trial is an open-label, prospective, multicenter, randomized phase III study. The aims of this study are to evaluate whether the the neoadjuvant regimen of mFOLFOX6 + Bevacizumab + PD-1 monoclonal antibody can improve the pathological complete response (pCR) rate, enhance survival outcomes, and maintain manageable toxicity compared to mFOLFOX6 alone in patients with locally advanced pMMR/MSS CRC. Eligible participants will be randomly assigned in a 1:1 ratio to either the experimental group or the control group. Participants in the experimental group will receive the neoadjuvant therapy regimen of mFOLFOX6 + Bevacizumab + PD-1 monoclonal antibody. And the first five doses will receive the neoadjuvant therapy regimen of mFOLFOX6 (intravenous oxaliplatin 85 mg/m2, leucovorin 400 mg/m2, 5-fluorouracil 400 mg/m2, and a 48-hour continuous infusion of 5-fluorouracil 2400 mg/m2) combined with sintilimab (200 mg, intravenous) and Bevacizumab (5 mg/kg, intravenous). The sixth dose will consist of the same regimen of mFOLFOX6 and PD-1 monoclonal antibody, but not plus bevacizumab, in order to allow sufficient withdrawal time of Bevacizumab for surgery. Participants in the control group will receive the neoadjuvant therapy regimen of mFOLFOX6 (intravenous oxaliplatin 85 mg/m2, leucovorin 400 mg/m2, 5-fluorouracil 400 mg/m2, and a 48-hour continuous infusion of 5-fluorouracil 2400 mg/m2) alone. Subjects in both the experimental and control groups will undergo radical surgical treatment after completing the neoadjuvant therapy. Those achieving pCR based on postoperative pathology will be regularly followed up according to the follow-up protocol. Participants who do not achieve pCR will receive six cycles of adjuvant therapy after surgery, followed by regular follow-up assessments as outlined in the protocol after completing the final cycle of adjuvant therapy. The primary outcome of this study is to evaluate the 3-year disease-free survival (DFS). Secondary objectives include the pCR rate, major pathological response (MPR) rate, neoadjuvant therapy-related toxicities, R0 resection rate, tumor downstaging rate, and overall survival (OS).