tilelizumab combined with nab-paclitaxel for high-risk non-muscle-invasive urothelial bladder carcinoma which is not completely resectable: a multi-center study

Conditions: High-Risk Non-Muscle Invasive Bladder Urothelial Carcinoma

Summary: this is a phase ii study to determine the safety and efficacy of tislelizumab when given in combination with nab-paclitaxel as treatment for patients with high-risk non-muscle-invasive bladder cancer (hr nmibc) which is not completely resectable. patients will receive treatment with tislelizumab in combination with nab-paclitaxel every 3 weeks for 4 treatment cycles over 12 weeks followed by transurethral resection biopsy.


Eligibility criteria:
inclusion criteria: 1. willing and able to provide written informed consent; 2. ability to comply with the protocol; 3. age ≥ 18 years; 4. high-risk non-muscle-invasive urothelial carcinoma or high-risk non-muscle-invasive urothelial carcinoma as the main pathological component \> 50%, difined as following: a. t1 b. high-grade ta c.carcinoma in situ(cis); 5. multi-point biopsy of bladder shows there are more than 2 section and over 3 points of pathological specimens are diagnosed as above, meanwhile, the tumor has to be diagnosed as not completely resectable by at least 2 senior urologist; 6. eastern cooperative oncology group (ecog) performance status of 0-2; 7. agreed to provide tissue examination samples (for detection of pd-l1 expression, tumor mutation load, ihc, detection of dna and rna, etc;) 8. organ function level must meet the following requirements: * hematological indexes: neutrophil count \>= 1.5x10\^9/l, platelet count \>= 80x10\^9/l, hemoglobin \>= 6.0 g/dl (can be maintained by blood transfusion); * liver function: total bilirubin \<=1.5 uln, alanine aminotransferase and aspartate aminotransferase \<=2.5 uln; 9. the subjects volunteered to join the study, signed informed consent, and had good compliance with follow-up; exclusion criteria: 1. receive live attenuated vaccine within 4 weeks before treatment or during the study period; 2. active, known or suspected autoimmune diseases; 3. history of primary immunodeficiency; 4. known history of allogeneic organ transplantation and allogeneic hematopoietic stem cell transplantation; 5. pregnant or lactating female patients; 6. untreated acute or chronic active hepatitis b or hepatitis c infection. under the condition of monitoring the virus copy number of patients receiving antiviral treatment, doctors can judge whether they are in line with the patients' individual conditions; 7. prior use of immunosuppressive drugs within 4 weeks prior to the start of treatment, excluding nasal and inhaled corticosteroids or physiological doses of systemic steroids (i.e. not more than 10 mg / day prednisolone or other corticosteroids with the same physiological dose); 8. known or suspected allergy to tislelizumab and albumin paclitaxel; 9. have a clear history of active tuberculosis; 10. received pd-1 / pd-l1 / ctla-4 antibody or other immunotherapy in the past; 11. participating in other clinical researchers; 12. men with reproductive capacity or women who are likely to become pregnant do not take reliable contraceptive measures; 13. uncontrolled concurrent diseases, including but not limited to: * hiv infected (hiv antibody positive); * severe infection in active stage or poorly controlled; * evidence of serious or uncontrollable systemic diseases (such as severe mental, neurological, epilepsy or dementia, unstable or uncompensated respiratory, cardiovascular, liver or kidney diseases, uncontrolled hypertension \[i.e. hypertension greater than or equal to ctcae grade 2 after drug treatment\]); * patients with active bleeding or new thrombotic disease

Keywords: tislelizumab nab-paclitaxe