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

NCT07448142 | Recruiting Phase 2 DMC

• 2 other identifiers: 2025-FXY-301B2025-700
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Colorectal Cancer (CRC)

Keywords

Colorectal cancer; Neoadjuvant therapy; Low-dose radiotherapy; Immunotherapy; Pucotenlimab; CAPEOX; Total neoadjuvant therapy; Organ preservation; Complete Response Rate; Disease-free survival; Overall survival

Outcome Measures

Primary Outcomes (1)

• Complete Response Rate (CR)

  The Combined CR rate is defined as the percentage of participants achieving either Clinical Complete Response (cCR) or Pathologic Complete Response (pCR). cCR is assessed via pelvic MRI, digital rectal examination (DRE), and endoscopy following the completion of 4 cycles of neoadjuvant therapy (each cycle is 21 days). For patients who do not achieve cCR and subsequently undergo radical surgery (scheduled 2-4 weeks after the last dose of neoadjuvant therapy), pCR is assessed by pathological examination of the resected surgical specimen (Tumor Regression Grading, TRG 0) according to the AJCC/College of American Pathologists (CAP) guidelines.

  From the start of neoadjuvant therapy until the completion of pre-operative assessment (approximately 12 weeks) and the time of surgery (approximately 14-16 weeks).

Secondary Outcomes (7)

• 3-year Disease-Free Survival (DFS)

  Up to 3 years after randomization.

• 5-year Overall Survival (OS)

  Up to 5 years after randomization.

• Distant Metastasis Rate

  Up to 5 years after randomization.

• R0 Resection Rate

  At the time of surgery.

• Postoperative Surgical Complication Rate

  Within 30 days after surgery.

Study Arms (2)

2 Gy LDRT + Pucotenlimab + CAPEOX

EXPERIMENTAL

Neoadjuvant low-dose radiotherapy (2 Gy) followed by pucotenlimab 200 mg IV Q3W plus CAPEOX chemotherapy.

Radiation: Low-dose radiotherapy; Drug: Pucotenlimab; Drug: CAPEOX/XELOX

5 Gy LDRT + Pucotenlimab + CAPEOX

EXPERIMENTAL

Neoadjuvant low-dose radiotherapy (5 Gy) followed by pucotenlimab 200 mg IV Q3W plus CAPEOX chemotherapy.

Radiation: Low-dose radiotherapy; Drug: Pucotenlimab; Drug: CAPEOX/XELOX

Interventions

Low-dose radiotherapy RADIATION

Low-dose radiotherapy delivered by linear accelerator to the primary rectal tumor and regional lymphatic drainage areas using IMRT or 3D-CRT techniques. Participants receive either 2 Gy or 5 Gy according to randomized assignment, administered prior to initiation of systemic neoadjuvant therapy.

2 Gy LDRT + Pucotenlimab + CAPEOX; 5 Gy LDRT + Pucotenlimab + CAPEOX

Pucotenlimab DRUG

Pucotenlimab is a programmed cell death protein 1 (PD-1) monoclonal antibody. It is administered at a fixed dose of 200 mg by intravenous infusion on Day 2 of each 21-day cycle, every 3 weeks (Q3W), during the neoadjuvant treatment phase.

2 Gy LDRT + Pucotenlimab + CAPEOX; 5 Gy LDRT + Pucotenlimab + CAPEOX

CAPEOX/XELOX DRUG

CAPEOX chemotherapy consists of oxaliplatin 130 mg/m² administered intravenously on Day 1 and capecitabine 1000-1250 mg/m² administered orally twice daily on Days 1-14 of each 21-day cycle during neoadjuvant therapy.

2 Gy LDRT + Pucotenlimab + CAPEOX; 5 Gy LDRT + Pucotenlimab + CAPEOX

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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

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.

Sponsors & Collaborators

• Sun Yat-sen University: lead

Study Sites (1)

Dept. of Colorectal Surgery, Sun Yat-sen University Cancer Center. Yuexiu District, Dongfeng East Road 651

Guangzhou, Guanggong, 510060, China

RECRUITING

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

Radiotherapy; XELOX

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Therapeutics

Study Officials

• Pei-Rong Ding

  Sun Yat-Sen University Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Wu Jiang

CONTACT

+86-15989120166; jiangwu@sysucc.org.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director of the Department of Colorectal Surgery

Study Record Dates

• First Submitted: February 9, 2026
• First Posted: March 4, 2026
• Study Start: March 15, 2026
• Primary Completion (Estimated): September 1, 2027
• Study Completion (Estimated): September 1, 2032
• Last Updated: May 7, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)