Disitamab Vedotin Combined With BCG Therapy in HER2-expressing High-risk Non-muscle Invasive Bladder Cancer

Prior treatment

• Upper urinary tract urothelial carcinoma(UTIC), except 2 years without recurrence after previous radical UTUC;
• Previously received other anti-HER-2 therapy;
• Active malignancy outside of the disease being treated by the study (i.e., disease progression or need for change in therapy within the past 24 months);Only the following special cases are allowed: a. Skin cancer treated within the last 24 months and completely cured; b. Adequately treated lobular carcinoma in situ (LCIS) and ductal CIS; c. History of localized breast cancer and receiving anti-hormonal drugs or history of localized prostate cancer (N0M0) and receiving androgen blockade therapy.
• Have not recovered from toxic effects of previous anticancer therapy (except for toxic effects of no clinical significance, such as alopecia, skin discoloration, neuropathy and hearing impairment).
• Major surgery within 4 weeks prior to day 1 of cycle 1 (TURBT not considered major surgery);

Other illness

• Evidence of locally advanced, metastatic, muscle-invasive, and/or extravesical bladder cancer;
• Evidence of active hepatitis B or C infection (e.g., subjects with hepatitis B who have a history of hepatitis C but have a normal polymerase chain reaction test result for hepatitis C virus and who are positive for antibodies to hepatitis B surface antigen may be enrolled in the study);

Lab values

• History of uncontrolled cardiovascular disease, Included: 1) presence of any of the following in the past 3 months: unstable angina, myocardial infarction, ventricular fibrillation, torsional ventricular tachycardia, cardiac arrest or known congestive New York Heart Association class III-IV heart failure, cerebrovascular accident, or transient ischemic attack. 2) Prolonged QTc intervals confirmed by ECG evaluation during screening(Fridericia; QTc\>480 ms). 3) Pulmonary embolism or other venous thromboembolism within the past 2 months.
• Known infection with human immunodeficiency virus (HIV), unless the subject has been on stable antiretroviral therapy for the past 6 months or longer and has not had an opportunistic infection in the past 6 months and has had a CD4 count \>350 in the past 6 months;

Other

• Histopathologic examination reveals any small cell component of the bladder, simple adenocarcinoma, simple squamous cell carcinoma or simple squamous CIS;
• Pregnant or lactating women;
• Delayed wound healing, defined as skin/decubitus ulcers, chronic leg ulcers, known gastric ulcers, or non-healing incisions;
• Other patients assessed by the investigator to be unsuitable for participation in this study.

• Age≥18 years;
• Histologically confirmed non-muscle-invasive urothelial cell carcinoma (UCC) of the bladder; A.Histopathology: any variant of UCC, The presence of any lymphovascular infiltration (LVI) was considered evidence of high risk. B. Confined to the mucosal (Ta, Tis) and lamina propria layers (T1) of the bladder. In addition, subjects had all visible tumors removed as completely as possible prior to the first dose of study drug and documented at baseline cystoscopy. C. CIS(Carcinoma in situ) does not require complete resection, but coexisting papillary carcinoma must be removed as completely as possible prior to enrollment and documented at baseline cystoscopy. Negative urine cytology results against malignant tumor cells are not required.
• Presence of HER2 expression (IHC 1+/2+/3+) by IHC in our pathology department;
• VHR(Very high risk) NMIBC, defined as having at least 1 of the following: Multiple and/or large (greater than \[\>\] 3 centimeters \[cm\]) T1, (HG/G3) tumors; T1, (HG/G3) tumor with concurrent CIS; T1, G3 with CIS in prostatic urethra; Micropapillary variant of non-muscle invasive urothelial carcinoma;
• Received first dose of medication ≤ 12 weeks from first TURBT;
• Refusal or unsuitability for radical cystectomy;
• Eastern Cooperative Oncology Group (ECOG) performance status of less than or equal to (\</=) 1;
• Adequate hematologic and end-organ function, Creatinine clearance \>/=30 milliliters per minute (mL/min) (calculated using the Cockcroft-Gault formula);
• Subjects (or their legal representatives) must sign an informed consent form (ICF);
• Females of childbearing potential must have a negative pregnancy test result (beta-hCG) (urine or serum) within 7 days prior to the first dose of study drug.