This multicenter, randomized controlled clinical trial (FIRM02 Study) aims to evaluate the effectiveness and safety of neoadjuvant mFOLFOX6 chemotherapy combined with PD-1 inhibitor (Serplulimab) in patients with MSS/pMMR locally advanced rectal cancer (LARC). A total of 128 patients with non-metastatic, untreated, locally advanced rectal cancer will be randomly assigned in a 1:1 ratio to either the experimental group (64 patients) or the control group (64 patients). The experimental group will receive 6 cycles of mFOLFOX6 chemotherapy combined with 3 mg/kg of Serplulimab every 2 weeks prior to surgery. The control group will receive 6 cycles of mFOLFOX6 chemotherapy alone. The primary endpoint is the pathological complete response (pCR), and secondary endpoints include major pathological response (MPR), tumor regression grade (TRG), overall response rate (ORR), and survival outcomes (DFS, RFS, and OS). Safety will be assessed based on adverse events and post-operative complications.
Rectal cancer patients with MRI showing the lower edge of the tumor within 15 cm of the anal verge, cT3-4 N any or cT any N1/2;
Pathologically confirmed adenocarcinoma, with pMMR (MLH1, MSH2, MSH6, and PMS2) positivity for all four proteins, or gene testing indicating microsatellite stability;
No complete bowel obstruction, or proximal colostomy relieving bowel obstruction;
Aged 18 to 75 years, regardless of gender;
Local invasion of surrounding organs by rectal tumor: Imaging tests suggest the tumor directly invades adjacent organs or structures, i.e., tumors with clinical stage cT4 below the peritoneal reflection or cT4b above the peritoneal reflection;
Patients with distant metastasis;
Previous treatment with any chemotherapy, radiotherapy, targeted therapy, or immunotherapy;
Active autoimmune diseases requiring systemic treatment (e.g., corticosteroids or immunosuppressants) within the past 2 years prior to enrollment;