Disitamab Vedotin Combined With Tislelizumab for Her2 Overexpressing High-Risk Non-Muscle-Invasive Urothelial Bladder Carcinoma Which is Not Completely Resectable

This is an interventional treatment trial for Her2 Overexpressing High-Risk Non-Muscle Invasive Bladder Urothelial Carcinoma focused on measuring Disitamab Vedotin, Tislelizumab Read More

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