Neoadjuvant Tisleizumab(BGB-A317) for dMMR/MSI-H Non-late Stage CRC Patients Before Surgery

Neoadjuvant Tisleizumab(BGB-A317) for dMMR/MSI-H Non-late Stage Colorectal Cancer Patients

According to the cancer statistics in 2020, colorectal cancer (CRC) remains a major public health issue worldwide, representing the third common cancer (10%) and second leading cause of death (9.4%) with 5-year survival rate approaching 65%. Meanwhile, 28.8% of the newly diagnosed cases and 30.3% of the CRC-related death occurs in China. Among all the CRC, stage I-III account for 75%. For the standard management for non-late stage(stage I-III) CRC patients, surgery including the primary site and local lymph nodes dissection has been the most important one. But for the high-risk stage II and locally-advanced stage III CRC, neoadjuvant or adjuvant therapy such as chemotherapy and radiotherapy plays a vital role in preventing the residual cancer cells to relapse and spread to distant sites after surgery. For the past decades, immunotherapy like anti-PD-1 and anti-CTLA4 checkpoint inhibitor achieves great process in solid tumor treatment especially for late-stage CRC. And Pembrolizumab and Nivolumab has been proved for dMMR/MSI-H late-stage-CRC by FDA. Combination of Ipilimumab and Nivolumab has achieved great success among the early-stage-CRC in NICHE study. The investigators here to carry out a phase II clinical trial to explore the safety and effect of single anti-PD-1 (Tisleizumab-BGB-A317 ) neoadjuvant treatment for non-late stage CRC patients.

Study Overview

• Status: Recruiting
• Conditions: Immunotherapy; DMMR Colorectal Cancer; Anti PD-1
• Intervention / Treatment: Drug: Tisleizumab(BGB-A317)

• Study Type: Interventional
• Enrollment (Estimated): 40
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Gong Chen, Prof; Phone Number: +86 020 87343584; Email: chengong@sysucc.org.cn
• Study Contact Backup: Name: Rong-xin Zhang, Prof; Phone Number: +86 020 87343584; Email: zhangrx@sysucc.org.cn

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510060
      • Recruiting
      • Sun Yat-sen University Cancer Center
      • Sub-Investigator: Rong-Xin Zhang, M.D.
      • Sub-Investigator: Yuan Li, M.D.
      • Sub-Investigator: Jian-Hong Peng, M.D.
      • Contact: Gong C Chen, Prof; Phone Number: +862087343584; Email: chengong@sysucc.org.cn
      • Sub-Investigator: Zhi-zhong Pan, Prof
      • Sub-Investigator: Xiao-jun Wu, Prof
      • Sub-Investigator: Zhen-hai Lu, Prof
      • Sub-Investigator: Pei-rong Ding, Prof
      • Sub-Investigator: Li-ren Li, Prof
      • Sub-Investigator: Fu-long Wang, M.D.
      • Sub-Investigator: Jun-zhong Lin, M.D.
      • Sub-Investigator: Ling-heng Kong, M.D.
      • Sub-Investigator: Cong Li, M.D.
      • Sub-Investigator: Wu Jiang, M.D.
      • Sub-Investigator: Wen-hua Fan, M.D.
      • Sub-Investigator: Wen-hao Zhou, M.D.
      • Sub-Investigator: Jing-hua Tang, M.D.
      • Sub-Investigator: Miaoqing Wu
      • Sub-Investigator: Di Cao
      • Sub-Investigator: Yi-fan Liu
      • Sub-Investigator: Da Kang

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Able to provide consents and agree to follow the trial requirement and assessment;
• Age >=18
• ECOG score: 0 or1
• Biopsy pathological diagnosis as MSI-H/dMMR( both IHC and PCR method required)
• Measurable and assessible primary tumor sites according to RECIST 1.1
• Able to provide 22ml peripheral blood for assessment for ctDNA
• With all organ function sufficient
• No bowel obstruction or fistula
• No previous chemotherapy, radiotherapy and immunotherapy accepted history
• Distant metastasis excluded before surgery by CT scan
• Contraception required for women for the whole enrollment time until 3 months after last dose of immunotherapy

Exclusion Criteria:

• self-autoimmune diseases history such as SLE
• People who using the immune suppressor
• Severe allergy to other mono-clone antibody
• Cerebral metastasis which hasn't be managed yet
• Hypertension(SBP>140mmHg，DBP>90mmHg)
• Uncontrolled diabetes(FBG>10mmol/L)
• Accepted anti-PD-1 or anti-PD-L1 immunotherapy in the past
• Uncontrolled heart diseases such as NYHA II heart failure, unstable angina , cardiac infarction in 1 year and arrhythmia
• Systemic inflammation which needs whole body treatment
• Urine routine: protein >=++ or 24hr urine protein>=1g
• Innate or acquired immune deficiency like HIV and HBV
• Enrolled in other clinical trial already
• Confirmed as metastasis before the surgery
• Other malignancies has been diagnosed before
• Tuberculosis
• Pregnancy

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: dMMR/MSI-H stage I-III CRC patients; Patients will accept 4 dose of Tisleizumab(BGB-A317) treatment after enrollment and the assessment of the therapeutic effect by clinicians would be finished after that. Once the patients has been qualified as cCR , they could be exempted for surgery and continued the watch and wait management. If the patient has been assessed as able to R0 surgery , then they would received surgery. Otherwise ,they would be excluded from the trial.

Drug: Tisleizumab(BGB-A317); 200mg i.v. q3w; Other Names: surgery

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
pathological complete regression rate	Patients without noninvasive or focal-invasive residues or involved lymph nodes should be considered as having achieved pCR. The rate is these patients over the whole group.	From enrollment to 1 year after surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
CR rate	Patients with non-invasive or focal-invasive or involved lymph nodes which persists for 4 weeks after neoadjuvant immunotherapy. The rate of these patients over the whole group.	From enrollment to 1 year after surgery
Major Pathological Response rate	Rate of the patients who had focal invasive and residue tumor site which less than 10% both in primary tumors and all lymph nodes.	From enrollment to 1 year after surgery
Disease free survival	The time interval between the enrollment to the events such as relapse, distant metastasis and progressed occured.	From enrollment to 1 year after surgery

Collaborators and Investigators

• Sponsor: Sun Yat-sen University
• Investigators: Principal Investigator: Gong Chen, Prof, Sun Yat-sen University

Study record dates

Study Major Dates

• Study Start (Actual): September 23, 2023
• Primary Completion (Estimated): November 30, 2024
• Study Completion (Estimated): December 31, 2025

Study Registration Dates

• First Submitted: November 3, 2022
• First Submitted That Met QC Criteria: February 15, 2024
• First Posted (Actual): February 16, 2024

Study Record Updates

• Last Update Posted (Actual): February 16, 2024
• Last Update Submitted That Met QC Criteria: February 15, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: CRC
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms; Antineoplastic Agents; Antineoplastic Agents, Immunological; Tislelizumab
• Other Study ID Numbers: 2021-FXY-471

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

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