A Clinical Trial Comparing Long-Course Versus Short-Course Radiotherapy Followed by Immunotherapy Combined With Total Neoadjuvant Therapy (TNT) to Long-Course Radiotherapy Followed by TNT in High-Risk Locally Advanced Rectal Cancer

NCT07113275 | Not Yet Recruiting Phase 3

• 1 other identifier: XHZDZLK
• Study Type: interventional
• Target: 435
• Locations: 1 country
• Sites: 1

Brief Summary

This study is a national multicenter, prospective randomized controlled Phase III clinical trial designed to investigate the potential therapeutic benefit of immunotherapy combined with total neoadjuvant therapy (TNT) and to compare the efficacy of different radiotherapy modalities followed by immunotherapy.

Conditions

Rectal Cancer; Total Neoadjuvant Therapy; Radiotherapy; Immunotherapy

Outcome Measures

Primary Outcomes (1)

• complete response (CR) rate

  Defined as pathological complete response (pCR) + Clinical complete response (cCR)

  an expected average of 12 months

Secondary Outcomes (3)

• 3-year event-Free Survival

  an expected average of 3 years

• Overall Survival

  an expected average of 5 years

• Adverse events (AEs) were graded according to the NCI CTCAE version 5·0

  an expected average of 1.5 years

Study Arms (3)

Group A: SCRT + iTNT

EXPERIMENTAL

Group A: SCRT + iTNT Radiotherapy (SCRT): Total dose 25 Gy delivered in 5 fractions (5 Gy per fraction, once daily over 5 consecutive days). Immunotherapy (HLX10): 300 mg via intravenous infusion every 3 weeks (q3w) for 6 cycles, initiated 1 week after radiotherapy completion. Chemotherapy (CAPEOX regimen): Oxaliplatin: 130 mg/m² IV infusion over 120 minutes on Day 1. Capecitabine: 1000 mg/m² orally twice daily (morning and evening, 30 minutes after meals) on Days 1-14. Cycle duration: 3 weeks per cycle; total of 6 cycles during the neoadjuvant phase. Then followed by a total mesorectal excision(TME) or Watch \& Wait strategy for clinical complete remission voluntary patients.

Radiation: Short-course radiotherapy; Drug: Capecitabine; Drug: Oxaliplatin; Drug: HLX10; Procedure: TME surgery

Group B: LCRT + iTNT

EXPERIMENTAL

Group B: LCRT + iTNT Radiotherapy with Concurrent Chemotherapy (LCRT): Total dose 50.4 Gy delivered in 28 fractions (1.8 Gy per fraction, once daily, 5 days per week). Concurrent Capecitabine: 825 mg/m² orally twice daily, 5 days per week (administered on radiotherapy days). Immunotherapy (HLX10): 300 mg IV infusion q3w for 6 cycles, initiated 2 weeks after radiotherapy completion. Chemotherapy (CAPEOX regimen): Oxaliplatin: 130 mg/m² IV infusion over 120 minutes on Day 1. Capecitabine: 1000 mg/m² orally twice daily (morning and evening, 30 minutes after meals) on Days 1-14. Cycle duration: 3 weeks per cycle; initiated 2 weeks post-radiotherapy; total of 6 cycles during the neoadjuvant phase. Then followed by a total mesorectal excision(TME) or Watch \& Wait strategy for clinical complete remission voluntary patients.

Radiation: Long-course radiotherapy; Drug: Capecitabine; Drug: Oxaliplatin; Drug: HLX10; Procedure: TME surgery

Group C: LCRT + TNT

ACTIVE COMPARATOR

Group C: LCRT + TNT Radiotherapy with Concurrent Chemotherapy (LCRT): Total dose 50.4 Gy delivered in 28 fractions (1.8 Gy per fraction, once daily, 5 days per week). Concurrent Capecitabine: 825 mg/m² orally twice daily, 5 days per week (administered on radiotherapy days). TNT Chemotherapy (CAPEOX regimen) with immunotherapy placebo: HLX10 placebo: 300 mg IV infusion q3w for 6 cycles, initiated 2 weeks after radiotherapy completion. Oxaliplatin: 130 mg/m² IV infusion over 120 minutes on Day 1. Capecitabine: 1000 mg/m² orally twice daily (morning and evening, 30 minutes after meals) on Days 1-14. Cycle duration: 3 weeks per cycle; initiated 2 weeks post-radiotherapy; total of 6 cycles during the neoadjuvant phase. Then followed by a total mesorectal excision(TME) or Watch \& Wait strategy for clinical complete remission voluntary patients.

Radiation: Long-course radiotherapy; Drug: Capecitabine; Drug: Oxaliplatin; Procedure: TME surgery; Drug: HLX10 placebo

Interventions

Short-course radiotherapy RADIATION

Eligible subjects will receive short-course radiotherapy (SCRT). One week after the end of treatment, subjects continued to receive neoadjuvant chemotherapy.

Also known as: SCRT

Group A: SCRT + iTNT

Long-course radiotherapy RADIATION

Long-course radiotherapy (LCRT, 50.4 Gy administered in 28 fractions) will be delivered concurrently with oral capecitabine.

Group B: LCRT + iTNT; Group C: LCRT + TNT

Capecitabine DRUG

1000mg/m2, bid, po, d1-14,q3w

Group A: SCRT + iTNT; Group B: LCRT + iTNT; Group C: LCRT + TNT

Oxaliplatin DRUG

130mg/m2, ivgtt, d1,q3w

Group A: SCRT + iTNT; Group B: LCRT + iTNT; Group C: LCRT + TNT

TME surgery PROCEDURE

The surgery was performed 1 week after the end of neoadjuvant therapy.

Group A: SCRT + iTNT; Group B: LCRT + iTNT; Group C: LCRT + TNT

HLX10 DRUG

300mg, ivgtt, q3w

Group A: SCRT + iTNT; Group B: LCRT + iTNT

HLX10 placebo DRUG

300mg, ivgtt, q3w

Group C: LCRT + TNT

Eligibility Criteria

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

You may qualify if:

• Patients or their family members agree to participate in the study and sign the informed consent form;
• Age 18-75 years, male or female;
• Histologically confirmed Locally Advanced rectal adenocarcinoma;
• Immunohistochemistry and/or genetic testing confirmed pMMR/MSS;
• inferior margin ≤ 10 cm from the anal verge;
• Pelvic MRI shows high risk \[meets one of the following conditions\]: • Clinical tumor (cT) staging cT4a or cT4b (according to AJCC 8th Edition) • Extramural vascular infiltration • Clinical lymph node (cN) staging cN2 (according to AJCC 8th Edition) • Mesenteric fascia is involved • Lateral lymph node enlargement
• ECOG performance status score is 0-1;
• Untreated with anti-tumor therapy for rectal cancer, including radiotherapy, chemotherapy, surgery, etc;
• There was no operative contraindication;
• Laboratory tests were required to meet the following requirements: white blood cell (WBC) ≥ 4×109/L; Absolute neutrophil count (ANC) ≥ 1.5×109/L; Platelet count ≥ 100×109/L; Hemoglobin ≥90 g/L; Serum total bilirubin ≤ 1.5 × upper limit of normal (ULN); Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 × ULN; Serum creatinine ≤1.5 times the upper limit of normal value or creatinine clearance rate ≥50 mL/min; International normalized ratio (INR) ≤ 1.5 × ULN; Activated partial thromboplastin time (APTT) ≤ 1.5 × ULN;
• Urinary protein \< 2+ or 24-hour urinary protein excretion \< 1 g at baseline.

You may not qualify if:

• Patients with non-high-risk pMMR LARC；
• Subjects who have previously received any form of immunotherapy, including but not limited to immune checkpoint inhibitors, immune checkpoint agonists, immune cell therapy, or any other treatment targeting tumor immunomodulatory mechanisms;
• Presence of any concurrent disease, condition (including laboratory abnormality), history of substance abuse, or current evidence thereof, which, in the judgment of the Investigator, may compromise subject safety, interfere with the process of obtaining informed consent, affect subject compliance, or confound the safety assessment of the investigational product(s).

Sponsors & Collaborators

• Tao Zhang: lead

Study Sites (1)

Union Hospital, Tongji Medical College, Huazhong University of Science and Technology

Wuhan, Hubei, 430022, China

Location

MeSH Terms

Conditions

Rectal Neoplasms

Interventions

Capecitabine; Oxaliplatin

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

Intervention Hierarchy (Ancestors)

Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Coordination Complexes; Organic Chemicals

Study Officials

• Zhenyu Lin, MD

  Union Hospital, Tongji Medical College, Huazhong University of Science and Technology

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Zhenyu Lin, MD

CONTACT

027-85871982; whxhlzy@hust.edu.cn

Tao Zhang, MD

CONTACT

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: MD

Study Record Dates

• First Submitted: August 2, 2025
• First Posted: August 8, 2025
• Study Start: February 11, 2026
• Primary Completion (Estimated): January 1, 2028
• Study Completion (Estimated): December 31, 2028
• Last Updated: February 12, 2026

Record last verified: 2025-07

Locations

CN (1)