NCT07296705招募中2 期
Selective Bladder Preservation After Neoadjuvant Zanidatamab Combined With Tislelizumab and Chemotherapy in Patients With HER2-Positive Muscle-Invasive Bladder Cancer: A Multicenter Study
干预措施
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 25
- 试验地点
- 12
- 主要终点
- Clinical Complete Response (cCR) Rate
研究概览
简要总结
This is a multicenter, open-label, prospective, single-arm, phase II study designed to evaluate the efficacy and safety of neoadjuvant zanidatamab combined with tislelizumab and chemotherapy, followed by selective bladder preservation, in patients with HER2-positive muscle-invasive bladder cancer (MIBC) staged cT2-4aN0-1M0.
详细描述
Eligible patients will receive neoadjuvant therapy with zanidatamab plus tislelizumab in combination with chemotherapy, followed by clinical reassessment. Patients who achieve a clinical complete response (cCR) will continue maintenance therapy with zanidatamab and tislelizumab. Patients who do not achieve cCR may, undergo radiotherapy or partial cystectomy and then continue maintenance zanidatamab plus tislelizumab; alternatively, they may proceed directly to radical cystectomy followed by adjuvant tislelizumab.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 85 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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-
- •Adequate organ function based on screening labs obtained ≤14 days before enrollment:
- •a. 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).
排除标准
- •Pregnant or breastfeeding women.
- •Uncontrolled infection requiring systemic therapy.
- •Diagnosis of another malignancy within the past 5 years.
- •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.
- •Active autoimmune disease requiring systemic treatment that, in the investigator's judgment, would affect study therapy.
- •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.
- •i. Note: If the initial ECG shows QTc >450 msec (men) or >470 msec (women), a follow-up ECG should be performed to confirm.
- •h) 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.
- •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.
- •Concurrent participation in another clinical study, unless observational (non-interventional) or in the follow-up phase of an interventional study.
- •Any other condition deemed by the investigator to render the patient ineligible.
研究组 & 干预措施
Experimental group
Experimental
干预措施: Zanidatamab (Drug)
Experimental group
Experimental
干预措施: Tislelizumab (Drug)
Experimental group
Experimental
干预措施: Cisplatin (Drug)
Experimental group
Experimental
干预措施: Gemcitabine (Drug)
Experimental group
Experimental
干预措施: Nab-paclitaxel (Drug)
结局指标
主要结局
Clinical Complete Response (cCR) Rate
时间窗: At the end of Cycle 4 of neoadjuvant therapy (each cycle is 21 days)
Proportion of participants achieving cCR at the end of neoadjuvant therapy, defined as no evidence of tumor on radiographic imaging, no residual tumor on diagnostic TURBT, and negative urine cytology
次要结局
- 1-Year Bladder-Intact Disease-Free Survival (BI-DFS)(From first neoadjuvant dose to 12 months)
- 2-Year Bladder-Intact Disease-Free Survival (BI-DFS)(From first neoadjuvant dose to 24 months)
- Local Recurrence Free Survival (LRFS)(From first neoadjuvant dose until event, assess up to 3 years)
- Distant Metastasis Free Survival (DMFS)(From first neoadjuvant dose until event, assess up to 3 years)
- Overall Survival (OS)(From first neoadjuvant dose until death, assess up to 3 years)
- Safety and Adverse Events(From first dose through last follow-up, assess up to 3 years)
- Quality of Life Assessed by EORTC QLQ-C30(From baseline through last follow-up, assess up to 3 years)
- Quality of Life Assessed by FACT-BI(From baseline through last follow-up, assess up to 3 years)
研究者
研究点 (12)
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