Neoadjuvant Tisleizumab(BGB-A317) for dMMR/MSI-H Non-late Stage CRC Patients Before Surgery
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.
- EligibilityCriteria: 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 - HealthyVolunteers: No - Gender: All - MinimumAge: 18 Years - StdAgeList: Adult, Older Adult