| Eligibility |
Inclusion Criteria:
1. Voluntary consent to participate in the study and sign an informed consent form.
2. Male or female, age = 18 years. 3. Disease satisfies.
- Diagnosis in accordance with the Chinese Guidelines for the Treatment of Bladder
Cancer (2022) high-risk non-muscle invasive bladder cancer (NMIBC) and meeting any of
the following ± carcinoma in situ (CIS): 1. stage T1 tumor of any grade; 2. high-grade
tumor; 3. multiple and/or recurrent tumors, with recurrent tumors excluding low-grade
solitary tumors.
- Histopathological satisfaction of uroepithelial carcinoma predominant by
histopathology, confirming the absence of muscular infiltration.
- Completion of TURBT and resection of all visible lesions within 3 weeks prior to study
dosing.
- Clinical staging (cTa/T1±CIS, N0, M0) and absence of distant metastases as assessed by
imaging (which needs to include at least CTU) within 3 months prior to enrollment.
4. 4. Prior BCG treatment.
1. Cohort 1 is high-risk NMIBC patients who have not received prior BCG therapy:
high-risk NMIBC patients who have not received prior BCG therapy due to
subjective and objective conditions, including one of the following 1. patient
refusal to receive BCG therapy; 2. presence of contraindications to BCG therapy;
3. BCG inaccessibility.
2. Cohort 2 was high-risk NMIBC patients with BCG non-response, and BCG non-response
met any of the following: 1. presence of persistent/recurrent high-risk NMIBC
within 12 months (±1 month) of completing adequate BCG therapy; 2. high-grade T1
disease at first assessment after induction phase BCG therapy. Note: Adequate BCG
therapy is defined as at least 5 BCG bladder instillations completed within 2
months and at least 2 BCG bladder instillations completed in any 6 consecutive
weeks over the next 10 months, i.e., at least "5+2" BCG bladder instillations
completed over an approximately 12-month period.
5. Subjects who have been assessed by a urologist to be unsuitable for radical bladder
cancer surgery or who have refused radical bladder cancer surgery.
6. Subjects whose tumor tissue obtained by TURBT within 3 weeks meets 1+, 2+ or 3+
HER2 expression by immunohistochemistry (IHC) at the study center.
7. ECOG physical status score of 0-2. 8. Adequate cardiac, bone marrow, liver, and
renal function, which should meet the following criteria within 7 days prior to study
dosing (normal values are based on the clinical trial center).
- Left ventricular ejection fraction = 50%.
- Hemoglobin = 9 g/dL.
- Absolute neutrophil count (ANC) = 1.5×109/L.
- Platelets = 100×109/L.
- Serum total bilirubin = 1.5 times the upper limit of normal (ULN).
- ALT and AST = 2.5×ULN.
- blood creatinine = 1.5 × ULN or creatinine clearance (CrCl) = 50 mL/min calculated
according to the Cockcroft-Gault formula method.
9. Female subjects should be surgically sterilized, post-menopausal, or agree to use
at least one medically approved contraceptive (e.g., IUD, pill, or condom) during
study treatment and for 6 months after the end of the study treatment period, and must
have a negative blood pregnancy test within 7 days prior to study enrollment;
false-positive results may be excluded by the investigator after enrollment. Male
subjects should agree to use at least one medically approved contraceptive during the
study treatment period and for 6 months after the end of the study treatment period.
10. be willing and able to comply with the trial and follow-up procedural
arrangements.
Exclusion Criteria:
1. muscle-invasive bladder cancer (T2 and above) and/or with regional lymph nodes and
distant metastases
2. Combined extra-vesical (i.e. urethral, ureteral or renal pelvis) uroepithelial
carcinoma.
3. Received any other antitumor therapy, such as chemotherapy, radiotherapy, targeted
therapy, immunotherapy, etc., within 4 weeks prior to study dosing, excluding 1 dose
of infusion chemotherapy completed immediately after TURBT.
4. Have not recovered from an adverse event caused by a previously applied antineoplastic
agent to CECAT 5.0 grade 0-1 within 2 weeks prior to the start of study dosing.
5. Those who have undergone major surgery within 4 weeks prior to the start of study
dosing or who are scheduled to undergo major surgery during the trial.
6. Serum virological tests (based on the normal values of the study center).
- Positive HBsAg or HBcAb test result with a positive HBVDNA copy number.
- Positive HCVAb test result together with a positive HCVRNA test result.
- Positive HIVAb test result.
7. live vaccine received within 4 weeks prior to the start of study dosing or scheduled
to receive any vaccine (except novel coronavirus vaccine) during the study period.
8. heart failure classified as grade 3 or higher by the New York Heart Association (NYHA)
of America.
9. the presence of a serious arterial/venous thrombotic event or cardiovascular accident
such as deep vein thrombosis, pulmonary embolism, cerebral infarction, cerebral
hemorrhage, or myocardial infarction within 6 months prior to study dosing, except for
lacunar cerebral infarction that is asymptomatic and does not require clinical
intervention
10. the presence of an active infection requiring systemic treatment, such as active
tuberculosis
11. the presence of active, unstably controlled systemic disease or serious comorbidity as
judged by the investigator, including diabetes mellitus, hypertension, cirrhosis,
interstitial pneumonia, obstructive pulmonary disease, complications that could cause
the subject to undergo intravesical therapy and/or general anesthesia
12. having any other disease, metabolic abnormality, physical examination abnormality or
laboratory test abnormality that, in the judgment of the investigator, gives reason to
suspect that the patient has a disease or condition that is inappropriate for the use
of the study drug or that will affect the interpretation of the study results, or that
places the patient at high risk
13. the presence of an active autoimmune disease requiring systemic therapy (e.g., use of
immunomodulatory drugs, corticosteroids, or immunosuppressants) prior to the start of
study dosing, allowing for associated replacement therapy (e.g., thyroxine for adrenal
or pituitary insufficiency, or replacement therapy with physiologic corticosteroids)
14. other malignancies within 5 years prior to the start of study dosing, with the
following exceptions.
- Malignancies that can be expected to resolve with treatment (including, but not
limited to, adequately treated thyroid cancer, cervical carcinoma in situ, basal
or squamous cell skin cancer, or radical surgically treated ductal carcinoma in
situ of the breast).
- Patients with prostate cancer with prior specific treatment (surgery or radiation
therapy).
1. T2N0M0 or earlier stage.
2. Gleason score = 7 and prostate-specific antigen (PSA) undetectable for at
least 1 year after anti-androgen therapy.
3. Patients with viable specific therapy or on active surveillance without
specific therapy, with stable disease 1 year prior to study entry.
15. previous history of allogeneic HSCT or organ transplantation
16. known hypersensitivity to recombinant humanized anti-HER2 monoclonal antibody-MMAE
coupling agent drug and its components or hypersensitivity to gemcitabine and any
excipients
17. women who are pregnant or breastfeeding.
18. estimated insufficient patient compliance to participate in this clinical study.
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