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

Immunotherapy Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06262581
• Other study ID #: 2021-FXY-471
• Status: Recruiting
• Phase: Phase 2
• Start date: September 23, 2023
• Est. completion date: December 31, 2025

Study information

• Verified date: February 2024
• Source: Sun Yat-sen University
• Contact: Gong Chen, Prof
• Phone: +86 020 87343584
• Email: chengong[@]sysucc.org.cn
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 40
• Est. completion date: December 31, 2025
• Est. primary completion date: November 30, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Colorectal Neoplasms
• DMMR Colorectal Cancer
• Immunotherapy

Intervention

Drug:
• Tisleizumab(BGB-A317)
200mg i.v. q3w

Locations

Country	Name	City	State
China	Sun Yat-Sen University Cancer Center	Guangzhou	Guangdong

Sponsors (1)

Lead Sponsor	Collaborator
Sun Yat-sen University

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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