Neoadjuvant Tisleizumab(BGB-A317) for dMMR/MSI-H Non-late Stage CRC Patients Before Surgery
- Conditions
- ImmunotherapyDMMR Colorectal CancerAnti PD-1
- Interventions
- Drug: Tisleizumab(BGB-A317)
- Registration Number
- NCT06262581
- Lead Sponsor
- Sun Yat-sen University
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 40
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description dMMR/MSI-H stage I-III CRC patients Tisleizumab(BGB-A317) 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.
- Primary Outcome Measures
Name Time Method pathological complete regression rate From enrollment to 1 year after surgery 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.
- Secondary Outcome Measures
Name Time Method CR rate From enrollment to 1 year after surgery 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.
Major Pathological Response rate From enrollment to 1 year after surgery Rate of the patients who had focal invasive and residue tumor site which less than 10% both in primary tumors and all lymph nodes.
Disease free survival From enrollment to 1 year after surgery The time interval between the enrollment to the events such as relapse, distant metastasis and progressed occured.
Trial Locations
- Locations (1)
Sun Yat-Sen University Cancer Center
🇨🇳Guangzhou, Guangdong, China