Low-Dose Radiotherapy to Sensitize Pucotenlimab Plus CAPEOX for pMMR Locally Advanced Rectal Cancer

Inclusion criteria

• Written informed consent provided prior to any study-specific procedures.
• Age 18 to 75 years at the time of enrollment.
• Histologically confirmed rectal adenocarcinoma.
• Tumor located within 10 cm from the anal verge, as assessed by endoscopy or imaging.
• Locally advanced disease, defined as clinical stage T2N+ or T3-T4a (any N) based on pelvic magnetic resonance imaging (MRI).
• Proficient mismatch repair (pMMR) or microsatellite-stable (MSS) tumor status confirmed by immunohistochemistry or molecular testing.
• No evidence of distant metastasis on preoperative imaging, including chest, abdominal, and pelvic computed tomography (CT).
• Circumferential resection margin (CRM) ≥2 mm and no involvement of the mesorectal fascia on baseline MRI.
• Eastern Cooperative Oncology Group (ECOG) performance status 0-1.
• Adequate organ function as defined by:
• Absolute neutrophil count ≥1.5 × 10⁹/L
• Platelet count ≥100 × 10⁹/L
• Hemoglobin ≥90 g/L
• Total bilirubin ≤1.5 × upper limit of normal (ULN)
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5 × ULN
• Creatinine clearance ≥50 mL/min
• Thyroid-stimulating hormone (TSH) within normal limits
• Women of childbearing potential must have a negative pregnancy test and agree to use effective contraception during the study and for a protocol-defined period after the last dose.
• Men with partners of childbearing potential must agree to use effective contraception during the study and for a protocol-defined period after the last dose.

Exclusion criteria

• Clinical T4b disease, defined as tumor invasion into adjacent organs or structures on baseline imaging.
• Circumferential resection margin (CRM) \<2 mm or definite involvement of the mesorectal fascia on baseline MRI.
• Evidence of distant metastasis outside the pelvis.
• Prior pelvic or abdominal radiotherapy.
• Prior treatment with immune checkpoint inhibitors or other systemic anticancer therapy for rectal cancer.
• Active or history of autoimmune disease requiring systemic treatment, except for conditions considered low risk for recurrence (e.g., vitiligo, resolved childhood asthma).
• Ongoing use of systemic immunosuppressive therapy, including corticosteroids equivalent to \>10 mg/day of prednisone, within 2 weeks prior to enrollment.
• Known human immunodeficiency virus (HIV) infection.
• Active hepatitis B virus infection with positive hepatitis B surface antigen and high viral load, or hepatitis C virus infection requiring treatment.
• Uncontrolled active infection or other serious medical condition that, in the investigator's judgment, would compromise patient safety or study compliance.
• History of another malignancy within 5 years, except for adequately treated basal cell carcinoma of the skin, cervical carcinoma in situ, or other malignancies with negligible risk of recurrence.
• Known hypersensitivity or allergy to pucotenlimab, oxaliplatin, capecitabine, or any of their excipients.
• Pregnant or breastfeeding women.
• Any condition that, in the investigator's opinion, makes the participant unsuitable for study participation.