Neoadjuvant mFOLFOX6 Chemotherapy Combined With Anti-PD-1 Therapy in MSS/pMMR Locally Advanced Rectal Cancer (FIRM02 Study)

Inclusion criteria

• 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;
• ECOG performance status: 0-1;
• Expected survival time ≥2 years;
• No previous chemotherapy, radiotherapy, targeted therapy, or immunotherapy;
• Laboratory test results meeting the following criteria during screening:Hematology: Neutrophil count ≥1.5×10⁹/L, platelet count ≥75×10⁹/L, hemoglobin ≥80 g/L; Liver function: AST and ALT ≤2.5× upper limit of normal (ULN); total bilirubin ≤1.5×ULN; Kidney function: Serum creatinine ≤1.5×ULN; Coagulation function: APTT ≤1.5×ULN, INR ≤1.5, PT ≤1.5×ULN; Urine protein: Urine protein ≤1+ (if ≥2+, 24-hour urine protein test required, and if result <1g, inclusion is allowed); Cardiac left ventricular ejection fraction ≥50%;
• Female participants must not be breastfeeding, and pregnancy test results must be negative;
• Voluntary signing of the informed consent form, with the ability to understand and comply with the study requirements.

Exclusion criteria

• 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;
• History of HIV infection, or active chronic hepatitis B or C (high viral DNA load);
• Currently receiving tuberculosis treatment or having received tuberculosis treatment in the past year prior to screening for active tuberculosis;
• Known or suspected allergy to the study drugs or any drug related to the study;
• Severe cardiovascular or cerebrovascular diseases;
• Severe active infection or uncontrollable infection requiring systemic treatment, or unexplained fever >38.5°C within 14 days before the first dose;
• Systemic corticosteroid treatment or other immunosuppressants within 14 days before the first dose, or immunostimulants within 4 weeks prior to the first dose;
• Clear history of neurological or psychiatric disorders, including epilepsy or dementia;
• Subjects who, for any other reason, may not be able to complete the study, or the investigator deems them unsuitable for inclusion;
• Refusal to sign the informed consent form.