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

Inclusion Criteria:

1. 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;
2. Pathologically confirmed adenocarcinoma, with pMMR (MLH1, MSH2, MSH6, and PMS2) positivity for all four proteins, or gene testing indicating microsatellite stability;
3. No complete bowel obstruction, or proximal colostomy relieving bowel obstruction;
4. Aged 18 to 75 years, regardless of gender;
5. ECOG performance status: 0-1;
6. Expected survival time ≥2 years;
7. No previous chemotherapy, radiotherapy, targeted therapy, or immunotherapy;
8. 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%;
9. Female participants must not be breastfeeding, and pregnancy test results must be negative;
10. Voluntary signing of the informed consent form, with the ability to understand and comply with the study requirements.

Exclusion Criteria:

1. 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;
2. Patients with distant metastasis;
3. Previous treatment with any chemotherapy, radiotherapy, targeted therapy, or immunotherapy;
4. Active autoimmune diseases requiring systemic treatment (e.g., corticosteroids or immunosuppressants) within the past 2 years prior to enrollment;
5. History of HIV infection, or active chronic hepatitis B or C (high viral DNA load);
6. Currently receiving tuberculosis treatment or having received tuberculosis treatment in the past year prior to screening for active tuberculosis;
7. Known or suspected allergy to the study drugs or any drug related to the study;
8. Severe cardiovascular or cerebrovascular diseases;
9. Severe active infection or uncontrollable infection requiring systemic treatment, or unexplained fever >38.5°C within 14 days before the first dose;
10. Systemic corticosteroid treatment or other immunosuppressants within 14 days before the first dose, or immunostimulants within 4 weeks prior to the first dose;
11. Clear history of neurological or psychiatric disorders, including epilepsy or dementia;
12. Subjects who, for any other reason, may not be able to complete the study, or the investigator deems them unsuitable for inclusion;
13. Refusal to sign the informed consent form.