Organ Preservation With Tislelizumab and Total Neoadjuvant Therapy in Patients With Low Rectal Cancer: RELIEVE -01 Study

A Single-arm, Multicenter, Phase II Clinical Study of Chemoradiotherapy Followed by Tislelizumab Combined With Chemotherapy for Organ Preservation in Resectable Low Rectal Cancer：the RELIEVE-01 Study

This is an open-label, multi-center, single-arm clinical study. All patients received concurrent chemoradiation therapy (CRT) followed by 4 cycles of tislelizumab combined with CAPOX, 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: Not yet recruiting
• Conditions: Rectal Cancer; RECTAL NEOPLASMS
• Intervention / Treatment: Radiation: Radiotherapy; Drug: Tislelizumab; Drug: Capecitabine; Drug: Oxaliplatin; Drug: Capecitabine

• Study Type: Interventional
• Enrollment (Estimated): 46
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Min Jian Xu, MD; Phone Number: 86-21-64041990; Email: xujmin@aliyun.com
• Study Contact Backup: Name: Tao Wen Tang, MD; Email: Tangwt1988@163.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 distance from the lower edge of the tumor to the anal verge is ≤5 cm through colonoscopy, digital anal examination or MRI
6. clinical stage cT1-3N1M0 or cT2-3N0M0 (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; CRT followed by 4 cycles of tislelizumab plus CAPOX and clinical response assessment: participants with CR (cCR+ pCR confirmed by local resection of ncCR): another 4 cycles of tislelizumab plus CAPOX and 9 cycles of tislelizumab, then watch and wait. participants with non-CR: underwent TME

Radiation: Radiotherapy; 45-50.4Gy in 25-28 fractions to the pelvis on Days 1-5 every week.; 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 CRT and 4 cycles of CAPOX plus tislelizumab.	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
• Collaborators: Shanghai Zhongshan Hospital; RenJi Hospital; First Hospital of China Medical University; Shanghai Changzheng Hospital; The Fourth Hospital of Hebei Medical University; Huadong Hospital; Liaoning Cancer Hospital & Institute

Study record dates

Study Major Dates

• Study Start (Estimated): May 1, 2024
• Primary Completion (Estimated): December 1, 2025
• Study Completion (Estimated): December 1, 2028

Study Registration Dates

• First Submitted: April 26, 2024
• First Submitted That Met QC Criteria: April 26, 2024
• First Posted (Actual): April 30, 2024

Study Record Updates

• Last Update Posted (Actual): April 30, 2024
• Last Update Submitted That Met QC Criteria: April 26, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: tislelizumab; organ preservation; low rectal cancer; watch and wait; TNT
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms; Rectal Neoplasms; Molecular Mechanisms of Pharmacological Action; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Antineoplastic Agents, Immunological; Capecitabine; Oxaliplatin; Tislelizumab
• Other Study ID Numbers: BGB-A317-2011-IIT

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