Neoadjuvant CAPOX With or Without Pucotenlimab Plus Selective Radiotherapy for Locally Advanced Rectal Cancer

NCT07528209 | Recruiting Phase 3 DMC

• 1 other identifier: B2026-234
• Study Type: interventional
• Target: 556
• Locations: 1 country
• Sites: 1

Brief Summary

This is a multicenter, phase III, randomized controlled trial. Eligible patients with pMMR/MSS locally advanced rectal cancer will be randomized in a 1:1 ratio to either the experimental group or the control group using stratified randomization, with mesorectal fascia (MRF) status as the stratification factor. Patients in the experimental group will receive four cycles of CAPOX plus pucotenlimab. Patients in the control group will receive four cycles of CAPOX alone. Tumor response will then be assessed. Patients with tumor shrinkage ≥20% and no persistent tumor involvement of the mesorectal fascia will proceed directly to surgery. Patients with tumor shrinkage \<20% or persistent MRF-positive disease will receive short-course radiotherapy, followed by two additional cycles of CAPOX plus pucotenlimab in the experimental group or CAPOX alone in the control group. After completion of neoadjuvant treatment, efficacy will be reassessed, and the timing of surgery will be determined according to treatment response. Postoperative adjuvant therapy will be decided by the investigator.

Conditions

Rectal Cancer; pMMR (Microsatellite Stable Rectal Cancer)

Keywords

Rectal cancer; Neoadjuvant Therapy; pMMR/MSS; Immunotherapy; Selective radiotherapy

Outcome Measures

Primary Outcomes (1)

• 3-year disease-free survival (DFS) rate

  DFS is defined for patients who are disease-free after surgery as the time from the postoperative baseline imaging assessment to the first occurrence of local recurrence, distant recurrence, or death from any cause, whichever occurs first.

  3 year

Secondary Outcomes (10)

• Complete response (CR) rate

  At completion of neoadjuvant treatment and surgery assessment

• Objective response rate (ORR)

  At completion of neoadjuvant treatment and surgery assessment

• R0 resection rate

  At completion of neoadjuvant treatment and surgery assessment

• Rate of radiotherapy use

  At completion of neoadjuvant treatment and surgery assessment

• Major pathological response (MPR) rate

  At completion of neoadjuvant treatment and surgery assessment

Study Arms (2)

Experimental group

EXPERIMENTAL

Patients in the experimental group will receive four cycles of CAPOX plus pucotenlimab. Tumor response will then be assessed. Patients with tumor shrinkage ≥20% and no persistent tumor involvement of the mesorectal fascia will proceed directly to surgery. Patients with tumor shrinkage \<20% or persistent MRF-positive disease will receive short-course radiotherapy, followed by two additional cycles of CAPOX plus pucotenlimab in the experimental group . After completion of neoadjuvant treatment, efficacy will be reassessed, and the timing of surgery will be determined according to treatment response. Postoperative adjuvant therapy will be decided by the investigator.

Drug: CAPOX

Control group

ACTIVE COMPARATOR

Patients in the control group will receive four cycles of CAPOX alone. Tumor response will then be assessed. Patients with tumor shrinkage ≥20% and no persistent tumor involvement of the mesorectal fascia will proceed directly to surgery. Patients with tumor shrinkage \<20% or persistent MRF-positive disease will receive short-course radiotherapy, followed by two additional cycles of CAPOX alone in the control group. After completion of neoadjuvant treatment, efficacy will be reassessed, and the timing of surgery will be determined according to treatment response. Postoperative adjuvant therapy will be decided by the investigator.

Drug: Pucotenlimab combine with CAPOX

Interventions

CAPOX DRUG

Oxaliplatin will be administered at 130 mg/m² intravenously over more than 2 hours on Day 1 every 3 weeks. Capecitabine will be administered orally at 1000 mg/m² twice daily on Days 1 through 14 every 3 weeks. Patients in the control group will receive four cycles of CAPOX alone. Tumor response will then be assessed. Patients with tumor shrinkage ≥20% and no persistent tumor involvement of the mesorectal fascia will proceed directly to surgery. Patients with tumor shrinkage \<20% or persistent MRF-positive disease will receive short-course radiotherapy, followed by two additional cycles of CAPOX alone in the control group. After completion of neoadjuvant treatment, efficacy will be reassessed, and the timing of surgery will be determined according to treatment response. Postoperative adjuvant therapy will be decided by the investigator.

Experimental group

Pucotenlimab combine with CAPOX DRUG

Pucotenlimab will be administered at 200 mg intravenously on Day 1 every 3 weeks. Oxaliplatin will be administered at 130 mg/m² intravenously over more than 2 hours on Day 1 every 3 weeks. Capecitabine will be administered orally at 1000 mg/m² twice daily on Days 1 through 14 every 3 weeks. Patients in the experimental group will receive four cycles of CAPOX plus pucotenlimab. Tumor response will then be assessed. Patients with tumor shrinkage ≥20% and no persistent tumor involvement of the mesorectal fascia will proceed directly to surgery. Patients with tumor shrinkage \<20% or persistent MRF-positive disease will receive short-course radiotherapy, followed by two additional cycles of CAPOX plus pucotenlimab in the experimental group . After completion of neoadjuvant treatment, efficacy will be reassessed, and the timing of surgery will be determined according to treatment response. Postoperative adjuvant therapy will be decided by the investigator.

Control group

Eligibility Criteria

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

You may qualify if:

• Age 18 to 75 years.
• Histologically confirmed rectal adenocarcinoma.
• The lower edge of the tumor is ≤12 cm from the anal verge.
• Clinical stage of cT3-4aN0M0 or cT1-4aN+M0 at initial diagnosis.
• Pre-treatment staging methods:
• Required: chest and abdominal CT and pelvic MRI. Optional: endorectal ultrasound or transrectal ultrasonography. For patients with contraindications to MRI, staging may be performed using CT combined with endorectal ultrasound or transrectal ultrasonography.
• pMMR status confirmed by immunohistochemistry on colonoscopic biopsy specimens at the pathology department of the study center, or MSS/MSI-L status confirmed by genetic testing (PCR-based or NGS-based methods).
• ECOG performance status 0-1.
• Voluntary participation in the study with written informed consent provided.
• No prior antitumor treatment for rectal adenocarcinoma, including but not limited to radiotherapy, chemotherapy, or surgery.
• Expected survival of at least 6 months.
• Adequate organ and bone marrow function, as defined below:
• Hematologic function No blood transfusion, hematopoietic growth factors, leukocyte-elevating agents, platelet-elevating agents, or anti-anemia therapy are allowed within 14 days before the first dose of study treatment.
• Absolute neutrophil count ≥1.5 × 10\^9/L Platelet count ≥100 × 10\^9/L Hemoglobin ≥60 g/L
• Biochemical function Serum albumin ≥30 g/L Total bilirubin ≤1.5 × upper limit of normal (ULN) ALT ≤2.5 × ULN AST ≤2.5 × ULN Alkaline phosphatase (ALP) ≤2.5 × ULN Serum creatinine ≤1.5 × ULN, or creatinine clearance (CrCl) ≥50 mL/min

You may not qualify if:

• Patients meeting any of the following criteria will be excluded:
• Clinical stage T4b disease.
• Positive lateral pelvic lymph nodes.
• Positive lateral pelvic lymph nodes are defined as either:
• a short-axis diameter ≥7 mm, or
• a short-axis diameter \<7 mm with at least two malignant imaging features, such as heterogeneous signal intensity, irregular shape, or spiculated margins.
• Predicted inability to preserve the anus. This is defined as tumor involvement of the dentate line and assessment by two senior colorectal surgeons that sphincter preservation is not feasible.
• Active autoimmune disease requiring systemic treatment within 2 years before enrollment, including but not limited to myasthenia gravis, systemic lupus erythematosus, interstitial pneumonitis, uveitis, ulcerative colitis, autoimmune hepatitis, hypophysitis, systemic vasculitis, nephritis, hyperthyroidism, hypothyroidism, or mixed connective tissue disease.
• Patients with vitiligo or childhood asthma that has completely resolved and requires no intervention in adulthood may be eligible.
• Asthma requiring bronchodilator therapy is not allowed. Replacement therapy, such as thyroxine, insulin, or physiologic corticosteroid replacement for adrenal or pituitary insufficiency, is not considered systemic treatment.
• Use of systemic corticosteroids within 14 days before the first dose of study treatment at a dose ≥10 mg/day prednisone equivalent, or use of other immunosuppressive agents, including but not limited to cyclosporine, cyclophosphamide, azathioprine, methotrexate, or thalidomide.
• Use of immunostimulatory agents such as interferon or interleukin-2 within 4 weeks before the first dose is also excluded.
• Receipt of a live vaccine or attenuated live vaccine within 30 days before the first dose, or planned vaccination with such vaccines during the study period.
• Broad-spectrum antibiotic therapy by any route within 30 days before the first dose.
• Prior antitumor therapy for rectal cancer, including radiotherapy, chemotherapy, surgery (except biopsy), PD-1/CTLA-4 dual immunotherapy, regorafenib, or any other tyrosine kinase inhibitor.

Sponsors & Collaborators

• Sun Yat-sen University: lead

Study Sites (1)

Sun Yat-sen University Cancer Center

Guangzhou, Guangdong, 510060, China

RECRUITING

MeSH Terms

Conditions

Rectal Neoplasms

Condition Hierarchy (Ancestors)

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

Study Officials

• Peirong Ding, M.D.

  Sun Yat-Sen University Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Kai Han, M.D

CONTACT

+86-18602042643; hankai@sysucc.org.cn

Study Design

• Study Type: interventional
• Phase: phase 3
• 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: April 7, 2026
• First Posted: April 14, 2026
• Study Start: April 20, 2026
• Primary Completion (Estimated): April 20, 2032
• Study Completion (Estimated): April 20, 2034
• Last Updated: April 30, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)