Low Rectal Cancer Treated With Total Neoadjuvant Therapy Plus Concurrent Tislelizumab Immunotherapy (TNTIT)

A Single-arm, Multicenter, Phase II Clinical Study of Total Neoadjuvant Therapy Plus Concurrent Tislelizumab Immunotherapy in Resectable Low Rectal Cancer

This is an open-label, multi-center, single-arm clinical study. All patients received 4-6 cycles total neoadjuvant therapy plus concurrent tislelizumab immunotherapy, then underwent clinical response assessment. Patients who achieved CR (cCR+ pCR confirmed by local resection of ncCR) continue tislelizumab combined with CAPOX for another 4 cycles and tislelizumab for 9 cycles, then Watch and Wait. Patients who did not achieved CR underwent total mesorectal excision (TME).

Study Overview

• Status: Recruiting
• Conditions: Rectal Cancer
• Intervention / Treatment: Drug: Tislelizumab; Drug: Capecitabine; Drug: Oxaliplatin; Drug: Capecitabine

• Study Type: Interventional
• Enrollment (Estimated): 50
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Jianmin Xu, MD; Phone Number: +862164041990; Email: xujmin@aliyun.com
• Study Contact Backup: Name: Wenju Chang, MD; Phone Number: 13764476150; Email: chang_erich@hotmail.com

Study Locations

• China
  • Shanghai Municipality
    • Shanghai, Shanghai Municipality, China, 200032
      • Recruiting
      • Shanghai Zhongshan Hospital, Shanghai
      • Contact: Wenju Chang, MD; Phone Number: 13764476150; Email: chang_erich@hotmail.com
      • Contact: Jianmin Xu, MD; Phone Number: 13501984869; Email: xujmin@aliyun.com

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Able to provide written informed consent, understand and comply with the requirements and evaluation schedule
2. ≥18, ≤75 years old
3. Histologically confirmed rectal adenocarcinoma
4. immunohistochemistry confirmed pMMR (positive for MLH1, MSH2, MSH6 and PMS2), or PCR /NGS confirmed MSI-L or MSS
5. The tumor is within 3 cm of the dentate line. through colonoscopy, digital anal examination or MRI
6. clinical stage cT1-3 N 0-1M0 (the 8th UICC/AJCC; T and N is evaluated by MRI)
7. Resectable primary tumor assessed by the Investigator
8. Have not received any anti-tumor treatment for rectal cancer
9. ECOG PS ≤ 1
10. Adequate organ function
11. Female subjects with the ability to become pregnant must have a serum pregnancy test with a negative result within 72 hours before the first dose, and be willing to use highly effective contraceptive methods during the trial and 120 days after the last dose. Male subjects whose partners are women of childbearing potential should be surgically sterilized or agree to use a highly effective method of contraception during the trial and for 120 days after the last dose.

Exclusion Criteria:

1. Histologically confirmed poorly differentiated/undifferentiated adenocarcinoma, mucinous adenocarcinoma and signet ring cell carcinoma
2. Have received any treatments for rectal cancer, or evidence of distant metastasis
3. Presence of following high risk factors assessed by MRI: MRF +, EMVI+, cN2, Positive lateral lymph nodes, T3d
4. Presence or in high risk of obstruction, perforation or bleeding;
5. Not suitable for long-course radiotherapy
6. Cannot tolerate surgery
7. ≥2 colorectal cancer lesions at the same time
8. Contraindications for MRI examination
9. Other malignant tumors in the past or at the same time
10. Have an active autoimmune disease requiring systemic therapy within the past 2 years
11. HIV infection
12. Untreated chronic hepatitis B or chronic hepatitis B virus (HBV) carriers (HBV DNA > 500 IU/mL) or active HCV carriers with detectable HCV RNA;
13. Hypersensitivity to any ingredient of tislelizumab, capecitabine, and oxaliplatin or to any component of the container
14. Other conditions judged by the researcher that do not meet the enrollment requirements

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: tislelizumab; All patients received 4-6 cycles total neoadjuvant therapy plus concurrent tislelizumab immunotherapy, then underwent clinical response assessment. Patients who achieved CR (cCR+ pCR confirmed by local resection of ncCR) continue tislelizumab combined with CAPOX for another 4 cycles and tislelizumab for 9 cycles, then Watch and Wait. Patients who did not achieved CR underwent total mesorectal excision (TME).

Drug: Tislelizumab; 200 mg IV on Day 1 of each 21-day cycle.; Drug: Capecitabine; Capecitabine 1000 mg/m2 orally twice daily (bid) on Day 1 to 14 of each 21-day cycle in CAPOX regimen; Drug: Oxaliplatin; 130 mg/m2 IV on Day 1 of each 21-day cycle in CAPOX regimen; Drug: Capecitabine; 825 mg/m2 orally twice daily (bid) 5 days/week during radiotherapy.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Complete Response rate (CR rate)	defined as the proportion of participants with clinical complete response(cCR) or near clinical complete response (ncCR) who achieved local resection confirmed pCR determined by the investigators after 4-6 cycles total neoadjuvant therapy plus concurrent tislelizumab immunotherapy.	From first dose up to 12 months, approximately

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
1/2/3 year organ-preservation rate	defined as the proportion of participants who survived and did not underwent TME in 1/2/3 year (in the CR set and full analysis set respectively)	From first dose of radiotherapy up to 36 months, approximately
1/2/3 year EFS rate	defined as the proportion of participants who did not develop local recurrence, distant metastasis, new invasive primary lesions of colorectal cancer, or death in 1/2/3 year (in the CR set, non-CR set and full analysis set respectively)	From first dose of radiotherapy up to 36 months, approximately
1/2/3 year OS rate	defined as the proportion of participants who survived in 1/2/3 year (in the full analysis set)	From first dose of radiotherapy up to 36 months, approximately
Percentage of Participants With Adverse Events	Percentage of Participants With adverse events (AEs) , immune-related adverse events(irAE) and serious adverse events (SAEs) per the National Cancer Institute CommonTerminology Criteria for Adverse Events (NCI CTCAE) Version 5.0	From first dose of radiotherapy up to 36 months, approximately

Collaborators and Investigators

• Sponsor: Fudan University

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2024
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): March 1, 2028

Study Registration Dates

• First Submitted: April 26, 2026
• First Submitted That Met QC Criteria: April 26, 2026
• First Posted (Actual): May 1, 2026

Study Record Updates

• Last Update Posted (Actual): May 1, 2026
• Last Update Submitted That Met QC Criteria: April 26, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Intestinal Diseases; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colorectal Neoplasms; Intestinal Neoplasms; Rectal Diseases; Rectal Neoplasms; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleic Acids, Nucleotides, and Nucleosides; Coordination Complexes; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Nucleosides; Uracil; Pyrimidinones; Deoxyribonucleosides; Fluorouracil; Capecitabine; Oxaliplatin; tislelizumab
• Other Study ID Numbers: TNTIT

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