Clinical trial NCT06262581: Neoadjuvant Tisleizumab(BGB-A317) for dMMR/MSI-H Non-late Stage CRC Patients Before Surgery
Official title: Neoadjuvant Tisleizumab(BGB-A317) for dMMR/MSI-H Non-late Stage Colorectal Cancer Patients
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: DMMR Colorectal Cancer
Anti PD-1
Immunotherapy
Keywords: CRC
Lead sponsor: Sun Yat-sen University
Sponsor class: OTHER
First posted: 2024-02-16
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: pathological complete regression rate
timeFrame: From enrollment to 1 year after surgery
Secondary outcomes:
measure: CR rate
timeFrame: From enrollment to 1 year after surgery
measure: Major Pathological Response rate
timeFrame: From enrollment to 1 year after surgery
measure: Disease free survival
timeFrame: From enrollment to 1 year after surgery
Other outcomes:
Locations:
city: Guangzhou
country: China
facility: Sun Yat-Sen University Cancer Center
state: Guangdong
Study officials:
affiliation: Sun Yat-sen University
name: Gong Chen, Prof
role: PRINCIPAL_INVESTIGATOR
References: