Yang et al. Anti-PD-1/CTLA-4 Dual Immunotherapy for LARC

Inclusion Criteria:

1. Age between 18 and 80 years; ECOG performance status 0-1;
2. Histopathologically confirmed rectal adenocarcinoma via colonoscopy; pMMR or MSS phenotype;
3. Rectal MRI stage II/III (excluding T4b); distal tumor margin ≤ 12 cm from the anal verge;
4. Willingness to comply with study procedures; consent to use tissue and blood samples for medical research purposes;
5. No prior history of radiotherapy, chemotherapy, or immunotherapy;
6. No immune system diseases (e.g., systemic lupus erythematosus, rheumatoid arthritis, systemic vasculitis, scleroderma, pemphigus, dermatomyositis, mixed connective tissue disease, hyperthyroidism/hypothyroidism, ulcerative colitis, autoimmune hemolytic anemia, HIV infection, etc.);
7. No severe cardiac, pulmonary, hepatic, or renal dysfunction; no jaundice or gastrointestinal obstruction;
8. No concurrent acute infection;
9. Baseline laboratory evaluations completed as required, with results obtained within 14 days before randomization, and laboratory values meeting the following criteria (per CTCAE 5.0):

   * White blood cell count ≥ 2000/μL;
   * Neutrophil count ≥ 1500/μL;
   * Platelet count ≥ 100×10³/μL;
   * Hemoglobin ≥ 9.0 g/dL;
   * Serum creatinine ≤ 1.5×upper limit of normal (ULN) or creatinine clearance \> 50 mL/min (female: creatinine clearance = \[140 - age (years)\] × body weight (kg) × 0.85 / (72 × serum creatinine (mg/dL)); male: creatinine clearance = \[140 - age (years)\] × body weight (kg) × 1.00 / (72 × serum creatinine (mg/dL)));
   * AST ≤ 3×ULN, ALT ≤ 3×ULN, total bilirubin ≤ 1.5×ULN;
10. No psychiatric/psychological disorders affecting social function;
11. Negative serum pregnancy test (blood HCG) within 1 week before randomization for women of childbearing potential;
12. Women of childbearing potential must agree to use effective contraception during the study period and for 5 months after the last dose of study drug;
13. Male subjects who are sexually active with women of childbearing potential must agree to use effective contraception during the study period and for 7 months after the last dose of study drug, and must refrain from sperm donation during this period.

Exclusion Criteria:

1. Multiple primary cancers or concurrent other malignant tumors;
2. Patients requiring emergency surgery due to intestinal obstruction, intestinal perforation, gastrointestinal bleeding, etc.;
3. Factors affecting oral drug absorption (e.g., inability to swallow, nausea/vomiting, diarrhea, intestinal obstruction, etc.);
4. Any uncontrolled, severe concomitant diseases;
5. Hypersensitivity to any component of the study drugs;
6. Expected survival \< 5 years for any reason;
7. Planned or previous organ/bone marrow transplantation;
8. Treatment with immunosuppressants or corticosteroids within 1 month before enrollment;
9. Central nervous system disorders that may impair ability to provide informed consent or comply with study procedures, as determined by the investigator;
10. Other conditions that may prevent completion of study treatment (e.g., alcoholism, drug addiction, etc.);
11. Pregnant or breastfeeding women.