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

Recruiting now · Phase 2

Conditions studied: Colorectal Cancer (CRC)

In brief

This is a prospective, open-label, randomized, parallel-group phase II trial evaluating the efficacy and safety of a low-dose radiotherapy sensitization strategy combined with a PD-1 antibody (pucotenlimab) and CAPEOX as neoadjuvant therapy in patients with pMMR/MSS locally advanced rectal adenocarcinoma. Participants will be randomized 1:1 to receive either 2 Gy or 5 Gy low-dose radiotherapy. Low-dose radiotherapy is delivered as a single fraction of 2 Gy (Arm A) or 5 Gy (Arm B). On the day after radiotherapy, participants will start pucotenlimab 200 mg IV Q3W (administered on Day 2 of each 21-day cycle) plus CAPEOX chemotherapy. Early response will be assessed after 2 cycles using endoscopy and pelvic MRI to guide subsequent treatment: participants with partial response may discontinue radiotherapy and continue neoadjuvant systemic therapy; participants with stable disease may switch to standard chemoradiotherapy; participants with progressive disease will receive multidisciplinary-team-guided salvage therapy. After 4 cycles, participants with clinical complete response may adopt a watch-and-wait strategy; otherwise, they will undergo radical surgery 2-4 weeks after completion of neoadjuvant therapy. Long-term follow-up will include recurrence and survival outcomes and quality of life.

Key facts

Study ID

NCT07448142

Run by

Sun Yat-sen University

People needed

50

Starts

2026-03-15

Expected to finish

2032-09-01

Last updated by the study team

2026-05-07

Who can join

Age: 18 and older, up to 75. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• 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.

You may not qualify if…

• 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.

Where it is running

• Dept. of Colorectal Surgery, Sun Yat-sen University Cancer Center. Yuexiu District, Dongfeng East Road 651 — Guangzhou, Guanggong, China (enrolling)

Full record on ClinicalTrials.gov

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