Short-course Radiotherapy in TNT Combined With Enlonstobart for pMMR LARC

Short-Course Radiotherapy in Total Neoadjuvant Therapy Combined With Enlonstobart for pMMR Locally Advanced Rectal Cancer: A Prospective, Multicenter, Open-Label, Randomized Controlled Trial

Efficacy and safety of short-course radiotherapy in total neoadjuvant therapy combined with enlonstobart for pMMR locally advanced rectal cancer

Study Overview

• Status: Not yet recruiting
• Conditions: Efficacy and Safety of Short-course Radiotherapy in Total Neoadjuvant Therapy Combined With Enlonstobart for pMMR Locally Advanced Rectal Cancer
• Intervention / Treatment: Drug: Experimental: short-course radiotherapy and immunotherapy; Drug: Chemoradiotherapy

• Study Type: Interventional
• Enrollment (Estimated): 128
• Phase: Phase 2

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 1.age >=18 years old, female and male. 2.Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. 3.Histologically confirmed adenocarcinoma of the colon, and umor biopsy immunohistochemistry (IHC) indicates pMMR .

  4.Staged as T3-4 NanyM0 or T1-2N+ M0 according to the AJCC 8th edition. 5.Rectal cancer: <10 cm from the anal verge. 6.Adequate organ function:

  1. Hematology : i. Absolute Neutrophil Count (ANC) ≥ 1.5 × 10⁹/L. ii. Platelet count ≥ 100 × 10⁹/L . iii. Hemoglobin ≥ 90 g/L.
  2. Hepatic: i. Serum Total Bilirubin (TBil) ≤ 1.5 × ULN (Upper Limit of Normal). ii. AST and ALT ≤ 2.5 × ULN. iii. Creatinine ≤ 1.5 × ULN ; Renal: Calculated Creatinine Clearance (CrCl) ≥ 60 mL/min (calculated using the Cockcroft-Gault formula)

  3. Coagulation: i. International Normalized Ratio (INR) and Activated Partial Thromboplastin Time (APTT) ≤ 1.5 × ULN.

     7. Men and women of childbearing potential must agree to use effective contraceptive measures during the study and for 6 months after the last treatment.

     8. Willing and able to voluntarily provide written informed consent and comply with all scheduled treatments and follow-up assessments.

     Exclusion Criteria:

     1. Pathological diagnosis of other special types, including but not limited to neuroendocrine carcinoma or squamous cell carcinoma.
     2. Has previously received radiotherapy, targeted agents, or immune checkpoint inhibitors for the treatment of rectal cancer.
     3. Active autoimmune disease, such as systemic lupus erythematosus or rheumatoid arthritis, necessitating ongoing immunosuppressive treatment.
     4. Has active infection, including but not limited to HIV, or positive HBV/HCV viral load requiring antiviral therapy for control and stabilization.
     5. Significant cardiovascular disease, such as myocardial infarction within 6 months prior to enrollment, unstable angina pectoris, or hypertension that remains uncontrolled above 160/100 mmHg despite optimal therapy.
     6. History of other malignant tumors, excluding non-melanoma skin cancer and cervical carcinoma in situ that have been curatively treated and disease-free for ≥ 5 years.
     7. Uncontrolled diabetes (HbA1c > 8%) or thyroid dysfunction requiring medication for abnormal TSH.
     8. Severe chronic intestinal conditions，including but not limited to Crohn's disease or active ulcerative colitis.
     9. The investigators believe that patients were inappropriate for participation.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: short-course radiotherapy and immunotherapy; patients will receive 5*5Gy short-course radiotherapy, followed by 4 cycles of CAPOX chemotherapy and Enlonstobart	Drug: Experimental: short-course radiotherapy and immunotherapy; patients will receive 5*5Gy short-course radiotherapy, followed by 4 cycles of CAPOX chemotherapy and Enlonstobart Enlonstobart 200mg IV every 3 weeks; Oxaliplatin 130mg/m2 IV Q3W d1 Capecitabine 1000mg/m2 bid d1-14 q3w
Active Comparator: chemoradiotherapy; Long-course radiotherapy +Capecitabine 825mg/m2 bid d1-d14, followed by 4 cycles of CAPOX chemotherapy	Drug: Chemoradiotherapy; Long-course radiotherapy +Capecitabine 825mg/m2 bid d1-d14, followed by 4 cycles of CAPOX chemotherapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
complete response Rate (pCR+cCR )	Clinical complete response or pathological complete response (cCR or pCR)	up to 2 year

Secondary Outcome Measures

Outcome Measure	Time Frame
Major pathologic response rate	up to 2 year
R0 resection rate	The R0 resection rate will be evaluated after surgery, an average of 4 weeks
3-year event-free survival (EFS) rate	up to 3 years
3-year overall survival (OS)	up to 3 years
Adverse Event	up to 2 year

Collaborators and Investigators

• Sponsor: Hebei Medical University Fourth Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): March 1, 2026
• Primary Completion (Estimated): March 1, 2026
• Study Completion (Estimated): June 30, 2030

Study Registration Dates

• First Submitted: February 25, 2026
• First Submitted That Met QC Criteria: February 25, 2026
• First Posted (Actual): March 4, 2026

Study Record Updates

• Last Update Posted (Actual): March 4, 2026
• Last Update Submitted That Met QC Criteria: February 25, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Therapeutics; Drug Therapy; Radiotherapy; Biological Therapy; Combined Modality Therapy; Immunomodulation; Chemoradiotherapy; Immunotherapy
• Other Study ID Numbers: CSPC-ESX-CRC-K01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No