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

NCT06262581 | Recruiting Phase 2

• 1 other identifier: 2021-FXY-471
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

DMMR Colorectal Cancer; Anti PD-1; Immunotherapy

Keywords

CRC

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (3)

• CR rate

  From enrollment to 1 year after surgery

• Major Pathological Response rate

  From enrollment to 1 year after surgery

• Disease free survival

  From enrollment to 1 year after surgery

Study Arms (1)

dMMR/MSI-H stage I-III CRC patients

EXPERIMENTAL

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)

Interventions

Tisleizumab(BGB-A317) DRUG

200mg i.v. q3w

Also known as: surgery

dMMR/MSI-H stage I-III CRC patients

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Sun Yat-sen University: lead

Study Sites (1)

Sun Yat-Sen University Cancer Center

Guangzhou, Guangdong, 510060, China

RECRUITING

MeSH Terms

Interventions

Surgical Procedures, Operative

Study Officials

• Gong Chen, Prof

  Sun Yat-sen University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Gong Chen, Prof

CONTACT

+86 020 87343584; chengong@sysucc.org.cn

Rong-xin Zhang, Prof

CONTACT

+86 020 87343584; zhangrx@sysucc.org.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: November 3, 2022
• First Posted: February 16, 2024
• Study Start: September 23, 2023
• Primary Completion: November 30, 2024
• Study Completion: December 31, 2025
• Last Updated: February 16, 2024

Record last verified: 2024-02

Locations

CN (1)