disitamab vedotin combined with tislelizumab for her2 overexpressing high-risk non-muscle-invasive urothelial bladder carcinoma which is not completely resectable

Conditions: Her2 Overexpressing High-Risk Non-Muscle Invasive Bladder Urothelial Carcinoma

Summary: this is a phase ii study to determine the safety and efficacy of disitamab vedotin when given in combination with tislelizumab as treatment for patients with her2 overexpressing high-risk non-muscle-invasive bladder cancer (hr nmibc) which is not completely resectable. patients will receive treatment with disitamab vedotin in combination with tislelizumab every 3 weeks for 4 treatment cycles over 12 weeks followed by transurethral resection biopsy.


Eligibility criteria:
inclusion criteria: 1. age ≥ 18 years; 2. urothelial carcinoma with her2 ihc 2+ or 3+; 3. 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); 4. 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; 5. agreed to provide tissue examination samples (for detection of pd-l1 expression, tumor mutation load, ihc, detection of dna and rna, etc;) 6. organ function level must meet or under the support treatment meet the following requirements: * hematological indexes: neutrophil count \>= 1.5x10\^9/l, platelet count \>= 100x10\^9/l, hemoglobin \>= 9.0 g/dl; * liver function: total bilirubin \<=1.5 uln, alanine aminotransferase and aspartate aminotransferase \<=2.5 uln（patient with metastatic liver cancer：aminotransferase \<=5.0 uln）; * renal function: creatinine ≤ 1.5 times the upper limit of normal, and creatinine clearance ≥ 50 ml/min; 7. the subjects volunteered to join the study, signed informed consent, and had good compliance with follow-up; exclusion criteria: 1. active, known or suspected autoimmune diseases; 2. history of primary immunodeficiency; 3. known history of allogeneic organ transplantation and allogeneic hematopoietic stem cell transplantation; 4. pregnant or lactating female patients; 5. 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; 6. 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); 7. known or suspected allergy to disitamab vedotin or tislelizumab; 8. have a clear history of active tuberculosis; 9. participating in other clinical researchers; 10. men with reproductive capacity or women who are likely to become pregnant do not take reliable contraceptive measures; 11. 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: disitamab vedotin tislelizumab