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

Sun Yat-sen University

Status and phase: Enrolling; Phase 2

Conditions: Anti PD-1; Immunotherapy; DMMR Colorectal Cancer

Treatments: Drug: Tisleizumab(BGB-A317)

Study type: Interventional

Funder types: Other

Identifiers

NCT06262581

2021-FXY-471

Details and patient eligibility

About

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.

Enrollment: 40 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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40 participants in 1 patient group

dMMR/MSI-H stage I-III CRC patients

Experimental group

Description:

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.

Treatment:

Drug: Tisleizumab(BGB-A317)