Neoadjuvant Zanidatamab + Tislelizumab + Chemotherapy for Selective Bladder Preservation in HER2-Positive MIBC

Korábbi kezelés

• Major surgery or significant trauma within 28 days prior to enrollment (placement of a vascular access device and TURBT are not considered major surgery).
• Prior radiotherapy to the bladder for bladder cancer.
• Concurrent participation in another clinical study, unless observational (non-interventional) or in the follow-up phase of an interventional study.

Más betegség

• Uncontrolled infection requiring systemic therapy.
• Diagnosis of another malignancy within the past 5 years.
• Active autoimmune disease requiring systemic treatment that, in the investigator's judgment, would affect study therapy.
• History of acute myocardial infarction or ischemic stroke within 6 months.
• Human immunodeficiency virus (HIV) infection (i.e., positive antibodies to HIV-1/2), active syphilis infection, or active tuberculosis infection.
• Active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection.
• History of interstitial lung disease, non-infectious pneumonitis, or uncontrolled pulmonary disease, including pulmonary fibrosis or acute lung disease.
• Known hypersensitivity to any study drug.
• Any other condition deemed by the investigator to render the patient ineligible.

Laborértékek

• Any of the following cardiovascular criteria:
  • Cardiac chest pain within ≤28 days before first study dose, defined as moderate pain that limits activities of daily living.
  • Symptomatic pulmonary embolism within ≤28 days before first study dose.
  • Any acute myocardial infarction within ≤6 months before first study dose.
  • Any history of heart failure of New York Heart Association (NYHA) Class III or IV within ≤6 months before first study dose.
  • Any ventricular arrhythmia of severity ≥ Grade 2 within ≤6 months before first study dose.
  • Any cerebrovascular accident within ≤6 months before first study dose.
  • Corrected QT interval (QTc by Fridericia): ≥470 msec for women or ≥450 msec for men.
  • Note: If the initial ECG shows QTc \>450 msec (men) or \>470 msec (women), a follow-up ECG should be performed to confirm.
  • Left ventricular ejection fraction (LVEF) ≤50% by multigated acquisition (MUGA) scan or echocardiography (ECHO). The same modality used at baseline must be used for follow-up assessments.

Egyéb

• Pregnant or breastfeeding women.

• Willing to participate, able to provide written informed consent, and able to understand and comply with study requirements and the assessment schedule.
• Age 18 to 85 years on the date of informed consent.
• Residual disease after TURBT; histologically confirmed urothelial carcinoma of the bladder staged cT2-T4aN0-1M0 per AJCC 8th edition by histology and imaging. For mixed histology, urothelial carcinoma must be predominant (≥50%).
• Availability of TURBT tumor tissue and corresponding pathology report; either fresh surgical tissue or unstained slides may be submitted.
• HER2-positive: IHC 2+ or 3+.
• No prior anti-HER2-directed therapy (including but not limited to HER2 antibodies, HER2-targeting ADCs, or HER2-targeted TKIs) and no prior PD-(L)1 therapy.
• ECOG performance status 0-2.
• Adequate organ function based on screening labs obtained ≤14 days before enrollment:
  • For the following counts, no growth-factor support within 14 days prior to sample collection: i. Absolute neutrophil count ≥ 1.5 × 10\^9/L ii. Platelets ≥ 100 × 10\^9/L iii. Hemoglobin ≥ 90 g/L b. INR or aPTT ≤ 1.5 × upper limit of normal (ULN) c. Total bilirubin ≤ 1.5 × ULN (≤ 3 × ULN for Gilbert syndrome or isolated indirect hyperbilirubinemia) d. AST, ALT, and alkaline phosphatase ≤ 2.5 × ULN
• Women of childbearing potential must have a negative urine or serum pregnancy test within ≤7 days before enrollment and agree to use highly effective contraception during the study and for ≥120 days after the last dose of zanidatamab, tislelizumab, or chemotherapy (whichever occurs later).
• Non-sterilized men must agree to use highly effective contraception during the study and for ≥120 days after the last dose of zanidatamab, tislelizumab, or chemotherapy (whichever occurs later).