New cocktail aims to shrink rectal tumors and save the sphincter

Copied word for word from the study's registry entry, so the wording is the study team's rather than ours.

Inclusion Criteria: * Histologically confirmed rectal adenocarcinoma. * pMMR status documented by immunohistochemistry (MSH1, MSH2, MSH6 and PMS2 all positive) or by MSI testing showing MSS or MSI-L. * Primary tumor located within 5 cm from the anal verge on pelvic MRI. * Clinical stage cT3-4bN0M0 or cTxN+M0, with or without positive mesorectal fascia (MRF) and/or extramural vascular invasion (EMVI), and assessed by the multidisciplinary team as resectable with the potential for R0 resection. * No clinical or radiologic evidence of bowel obstruction. * No prior colorectal surgery. * No prior chemotherapy or radiotherapy. * No prior treatment with biologic agents (e.g., monoclonal antibodies), immune checkpoint inhibitors (e.g., anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CTLA-4), or other investigational drugs. * Age 18 to 75 years (inclusive). * Eastern Cooperative Oncology Group (ECOG) performance status 0-1. * Estimated life expectancy \> 2 years. * Adequate bone marrow function: WBC \> 3.5 × 10\^9/L; platelets \> 100 × 10\^9/L; hemoglobin \> 80 g/L. * Adequate liver function: ALT and AST ≤ 1.5 × upper limit of normal (ULN); total bilirubin \< 23.0 μmol/L. * Adequate renal function: eGFR ≥ 60 mL/min/1.73 m² (CKD-EPI) or creatinine clearance (Ccr) ≥ 60 mL/min. * Ability to understand and willingness to sign a written informed consent form. Exclusion Criteria: * Evidence of inguinal or lateral pelvic lymph node metastasis (lymph node short-axis diameter ≥ 7 mm or MRI features typical for metastatic lymph nodes). * Clinically significant cardiac disease, including arrhythmias requiring anti-arrhythmic treatment (except β-blockers or digoxin), symptomatic coronary artery disease or myocardial ischemia (myocardial infarction within the last 6 months), or congestive heart failure \> NYHA class II. * Uncontrolled severe hypertension. * History of HIV infection or active chronic hepatitis B (HBV DNA \> 2 × 10\^3 IU/mL) or hepatitis C (HCV RNA \> 1 × 10\^3 IU/mL). * Active pulmonary tuberculosis under treatment or having received anti-tuberculosis therapy within 1 year before screening. * Other active severe infections (as defined by NCI-CTCAE v5.0). * Evidence of distant metastasis outside the pelvis before treatment. * Cachexia or decompensated organ dysfunction. * Prior pelvic or abdominal radiotherapy. * Multiple primary colorectal cancers. * History of seizures requiring ongoing treatment (e.g., corticosteroids or anti-epileptic drugs). * History of another malignancy within the past 5 years, except adequately treated cervical carcinoma in situ or basal cell carcinoma of the skin. * Drug or alcohol abuse, or any medical, psychological, or social condition that, in the investigator's judgment, could interfere with study participation or the evaluation of study results. * Any active autoimmune disease or history of autoimmune disease (including but not limited to interstitial pneumonia, uveitis, colitis, hepatitis, hypophysitis, nephritis, hyperthyroidism, or hypothyroidism). * Receipt of any prophylactic vaccine against infectious diseases (e.g., influenza, varicella) within 4 weeks before enrollment. * Requirement for long-term immunosuppressive therapy or systemic/local corticosteroids at immunosuppressive doses (equivalent to \> 10 mg/day of prednisone or other corticosteroids). * Known or suspected allergy or hypersensitivity to any study drug or to any component of the study treatments. * Any unstable condition or other circumstance that may, in the opinion of the investigator, compromise patient safety or study compliance. * Pregnant or breastfeeding women, or women of childbearing potential who are unwilling or unable to use adequate contraception during the study. * Refusal or inability to provide written informed consent.