A Study to Evaluate the Efficacy and Safety of Intravesical Instillation of Disitamab Vedotin Combined With Toripalimab in Patients With HER2-Positive High-Risk Non-Muscle Invasive Bladder Cancer Who Are BCG-Naïve or Have BCG Failure

Inclusion criteria

• Voluntarily agree to participate in the research and sign the informed consent form.
• Within 3 weeks after TURBT surgery, the tumor tissue specimens obtained from the subjects were subjected to immunohistochemical (IHC) testing for HER2 expression, which met the criteria of 1+, 2+ or 3+. If the IHC result was 2+, FISH verification for amplification was required.
• ECOG physical condition: 0 - 2 points.
• Sufficient heart, bone marrow, liver and kidney functions should meet the following standards within 7 days before the drug administration study (normal values are based on the clinical trial center): Left ventricular ejection fraction ≥ 50%; Hemoglobin ≥ 9 g/dL; Absolute neutrophil count (ANC) ≥ 1.5 × 10^9/L; Platelets ≥ 100 × 10^9/L; Serum total bilirubin ≤ 1.5 times the upper limit of normal value (ULN); ALT and AST ≤ 2.5 × ULN; Serum creatinine ≤ 1.5 × ULN or calculated creatinine clearance rate (CrCl) ≥ 50 mL/min according to the Cockcroft-Gault formula.
• Within 3 weeks after TURBT surgery, the tumor tissue specimens obtained from the subjects were subjected to immunohistochemical (IHC) testing for HER2 expression, which met the criteria of 1+, 2+ or 3+. If the IHC result was 2+, FISH verification for amplification was required.
• ECOG physical condition: 0 - 2 points.
• Sufficient heart, bone marrow, liver and kidney functions should meet the following standards within 7 days before the drug administration study (normal values are based on the clinical trial center): Left ventricular ejection fraction ≥ 50%; Hemoglobin ≥ 9 g/dL; Absolute neutrophil count (ANC) ≥ 1.5 × 10^9/L; Platelets ≥ 100 × 10^9/L; Serum total bilirubin ≤ 1.5 times the upper limit of normal value (ULN); ALT and AST ≤ 2.5 × ULN; Serum creatinine ≤ 1.5 × ULN or calculated creatinine clearance rate (CrCl) ≥ 50 mL/min according to the Cockcroft-Gault formula.
• The female subjects should be patients who have undergone surgical sterilization or menopause, or those who agree to use at least one medically approved contraceptive method (such as intrauterine device, contraceptive pills or condoms) during the study treatment period and within 6 months after the end of the study treatment. The blood pregnancy test must be negative within 7 days before the subject is enrolled in the study. False positive results can be excluded after confirming pregnancy by the investigator and then the subject can be enrolled. Male subjects should agree to use at least one medically approved contraceptive method during the study treatment period and within 6 months after the end of the study treatment.
• Willing and able to comply with the arrangements of the trial and follow-up procedures.
• Willing and able to comply with the arrangements of the trial and follow-up procedures.

Exclusion criteria

• Muscle-invasive bladder cancer (T2 and above) and/or those with regional lymph node and distant metastasis.
• Combined urinary tract urothelial carcinoma outside the bladder (i.e., in the urethra, ureters or renal pelvis).
• The study excluded any patients who had received any other anti-tumor treatments within 4 weeks prior to the administration of the drug, such as chemotherapy, radiotherapy, targeted therapy, immunotherapy, etc. This exclusion did not include the one-time perfusion chemotherapy immediately performed after TURBT.
• Before the start of the drug study, there was no recovery from the adverse events caused by the previously used anti-tumor drugs to the 0-1 level of CECAT within 2 weeks.
• Those who started the drug administration within 4 weeks before the study or those who planned to undergo major surgery during the trial period.
• Serological virological examination (based on the normal values of the research center): HBsAg or HBcAb test results are positive, and HBVDNA copy number is also positive; HCVAb test result is positive, and HCV RNA test result is also positive; HIVAb test result is positive.
• The study excluded participants who had received live vaccines within 4 weeks prior to the start of the treatment or who planned to receive any vaccines during the study period (except for the novel coronavirus inactivated virus vaccine).
• Heart failure classified as grade 3 or above by the New York Heart Association (NYHA) in the United States.
• The study excluded cases where there had been severe arterial/venous thrombosis events or cardiovascular/cerebrovascular accidents within 6 months before administration, such as deep vein thrombosis, pulmonary embolism, cerebral infarction, cerebral hemorrhage, myocardial infarction, etc. However, cases of asymptomatic and non-requirement-of-clinical-intervention lacunar cerebral infarction were included.
• There are active or progressive infections that require systematic treatment, such as active tuberculosis.
• There are systemic diseases that have been judged by the researchers to be active and not yet under stable control, as well as severe comorbidities, including diabetes, hypertension, liver cirrhosis, interstitial pneumonia, obstructive pulmonary disease, etc.
• Previous history of receiving allogeneic hematopoietic stem cell transplantation or organ transplantation.
• Those who are known to be allergic to RC48-ADC/Teripipor or any of its components or any of the excipients.
• Pregnant or lactating women.
• It is estimated that the patient's compliance with this clinical study is insufficient.