Neoadjuvant Radiotherapy Combined With NALIRIFOX and Adebrelimab in pMMR/MSS Locally Advanced Rectal Cancer: A Prospective, Randomized, Phase II Clinical Trial

Inclusion criteria

• Patients or their family members agree to participate in the study and sign the informed consent form;
• Age 18-75 years, male or female;
• Locally advanced rectal adenocarcinoma confirmed by histopathology;
• Clinical stage cT3-4bN0M0 or cTxN+M0, with or without MRF positive, with or without EMVI positive, expected to R0 resection;
• without intestinal obstruction;
• ECOG PS 0-1;
• expect survival up to 2 years;
• White blood cell count > 3.5×109/L；Platelet count ≥ 100×109/L；Hemoglobin ≥ 80 g/L；
• ALT ≤ 1.5×ULN, AST ≤ 1.5×ULN ；
• Serum creatinine ≤ 100μmol/l,

Exclusion criteria

• With inguinal lymph node metastasis or lateral lymph node metastasis (lymph node diameter ≥7 mm, or lymph node morphology and MRI features consistent with typical metastatic lymph nodes);
• Arrhythmia requiring antiarrhythmic treatment (except beta-blockers or digoxin), symptomatic coronary artery disease or myocardial ischemia (myocardial infarction within the last 6 months), or congestive heart failure exceeding NYHA Class II;
• Severe hypertension poorly controlled with medication;
• History of HIV infection, or active hepatitis B (HBV DNA ≥ 2000 IU/mL or 10⁴ copies/mL), or hepatitis C (positive hepatitis C antibody with HCV-RNA above the lower limit of detection of the assay);
• Active pulmonary tuberculosis (TB), currently receiving anti-tuberculosis treatment, or having received anti-tuberculosis treatment within 1 year prior to screening;
• Other active clinically severe infections (NCI-CTCAE Version 5.0);
• Preoperative evidence of distant metastasis outside the pelvis;
• Cachexia or organ function decompensation.
• History of pelvic or abdominal radiotherapy;
• Multiple primary colorectal cancers;
• Patients with seizures requiring treatment (e.g., corticosteroids or antiepileptic therapy);
• History of other malignancies within 5 years, except cured cervical carcinoma in situ or basal cell carcinoma of the skin;
• Drug abuse, or medical, psychological, or social conditions that may interfere with the patient's participation in the study or affect the evaluation of study results;
• Active autoimmune disease or history of autoimmune disease (including but not limited to: interstitial pneumonia, uveitis, enterocolitis, hepatitis, hypophysitis, nephritis, hyperthyroidism, and hypothyroidism);
• Receipt of any anti-infective vaccine (e.g., influenza vaccine, varicella vaccine, etc.) within 4 weeks prior to enrollment;
• Comorbidities requiring long-term treatment with immunosuppressive agents, or requiring systemic or local administration of corticosteroids at immunosuppressive doses (dose >10 mg/day of prednisone or other glucocorticoids with equivalent efficacy);
• Known or suspected hypersensitivity to the investigational drug, or to any medication administered in relation to this study;
• Any unstable condition that may jeopardize patient safety or compliance;
• Pregnant or lactating women, or women of childbearing potential not using adequate contraception;
• Refusal to sign the informed consent form.