Neoadjuvant Zanidatamab + Tislelizumab + Chemotherapy for Selective Bladder Preservation in HER2-Positive MIBC
NCT ID: NCT07296705
Last Updated: 2025-12-22
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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RECRUITING
PHASE2
25 participants
INTERVENTIONAL
2025-10-25
2029-12-31
Brief Summary
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Detailed Description
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Conditions
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Study Design
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NA
SINGLE_GROUP
TREATMENT
NONE
Study Groups
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Experimental group
Zanidatamab
Zanidatamab (1,800 mg for patients \<70 kg or 2,400 mg for patients ≥70 kg, administered intravenously every 3 weeks) for 4 cycles is given as part of the neoadjuvant regimen. After completion of neoadjuvant therapy, disease status is reassessed. Patients achieving a clinical complete response (cCR) may continue zanidatamab every 3 weeks for 2-4 cycles as part of bladder-preserving treatment; those without cCR may receive radiotherapy or partial cystectomy followed by zanidatamab every 3 weeks for 2-4 cycles, or undergo radical cystectomy without further zanidatamab treatment.
Tislelizumab
Tislelizumab (200 mg administered intravenously every 3 weeks) is administered for 4 cycles as neoadjuvant therapy. After completion of 4 cycles, disease status is reassessed. Patients achieving a clinical complete response (cCR) may proceed with selective bladder preservation and continue tislelizumab every 3 weeks for 12 cycles; those without cCR may receive radiotherapy or partial cystectomy followed by tislelizumab every 3 weeks for 12 cycles, or undergo radical cystectomy with adjuvant tislelizumab every 3 weeks for 12 cycles.
Cisplatin
Cisplatin (70 mg/m² administered intravenously every 3 weeks ) for 4 cycles is included in the neoadjuvant chemotherapy regimen for eligible cisplatin-based chemotherapy.
Gemcitabine
Gemcitabine (1,000 mg/m² administered intravenously every 3 weeks) for 4 cycles is given as part of the neoadjuvant chemotherapy regimen for eligible cisplatin-based chemotherapy.
Nab-paclitaxel
Nab-paclitaxel (125 mg/m² administered intravenously every 3 weeks) for 4 cycles is given as part of the neoadjuvant chemotherapy regimen for ineligible or refused cisplatin-based chemotherapy.
Interventions
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Zanidatamab
Zanidatamab (1,800 mg for patients \<70 kg or 2,400 mg for patients ≥70 kg, administered intravenously every 3 weeks) for 4 cycles is given as part of the neoadjuvant regimen. After completion of neoadjuvant therapy, disease status is reassessed. Patients achieving a clinical complete response (cCR) may continue zanidatamab every 3 weeks for 2-4 cycles as part of bladder-preserving treatment; those without cCR may receive radiotherapy or partial cystectomy followed by zanidatamab every 3 weeks for 2-4 cycles, or undergo radical cystectomy without further zanidatamab treatment.
Tislelizumab
Tislelizumab (200 mg administered intravenously every 3 weeks) is administered for 4 cycles as neoadjuvant therapy. After completion of 4 cycles, disease status is reassessed. Patients achieving a clinical complete response (cCR) may proceed with selective bladder preservation and continue tislelizumab every 3 weeks for 12 cycles; those without cCR may receive radiotherapy or partial cystectomy followed by tislelizumab every 3 weeks for 12 cycles, or undergo radical cystectomy with adjuvant tislelizumab every 3 weeks for 12 cycles.
Cisplatin
Cisplatin (70 mg/m² administered intravenously every 3 weeks ) for 4 cycles is included in the neoadjuvant chemotherapy regimen for eligible cisplatin-based chemotherapy.
Gemcitabine
Gemcitabine (1,000 mg/m² administered intravenously every 3 weeks) for 4 cycles is given as part of the neoadjuvant chemotherapy regimen for eligible cisplatin-based chemotherapy.
Nab-paclitaxel
Nab-paclitaxel (125 mg/m² administered intravenously every 3 weeks) for 4 cycles is given as part of the neoadjuvant chemotherapy regimen for ineligible or refused cisplatin-based chemotherapy.
Eligibility Criteria
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Inclusion Criteria
2. Age 18 to 85 years on the date of informed consent.
3. 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%).
4. Availability of TURBT tumor tissue and corresponding pathology report; either fresh surgical tissue or unstained slides may be submitted.
5. HER2-positive: IHC 2+ or 3+.
6. 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.
7. ECOG performance status 0-2.
8. 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
9. 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).
10. 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).
Exclusion Criteria
2. Uncontrolled infection requiring systemic therapy.
3. Diagnosis of another malignancy within the past 5 years.
4. Major surgery or significant trauma within 28 days prior to enrollment (placement of a vascular access device and TURBT are not considered major surgery).
5. Prior radiotherapy to the bladder for bladder cancer.
6. Active autoimmune disease requiring systemic treatment that, in the investigator's judgment, would affect study therapy.
7. Any of the following cardiovascular criteria:
1. Cardiac chest pain within ≤28 days before first study dose, defined as moderate pain that limits activities of daily living.
2. Symptomatic pulmonary embolism within ≤28 days before first study dose.
3. Any acute myocardial infarction within ≤6 months before first study dose.
4. Any history of heart failure of New York Heart Association (NYHA) Class III or IV within ≤6 months before first study dose.
5. Any ventricular arrhythmia of severity ≥ Grade 2 within ≤6 months before first study dose.
6. Any cerebrovascular accident within ≤6 months before first study dose.
7. 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.
8. History of acute myocardial infarction or ischemic stroke within 6 months.
9. Human immunodeficiency virus (HIV) infection (i.e., positive antibodies to HIV-1/2), active syphilis infection, or active tuberculosis infection.
10. Active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection.
11. History of interstitial lung disease, non-infectious pneumonitis, or uncontrolled pulmonary disease, including pulmonary fibrosis or acute lung disease.
12. Known hypersensitivity to any study drug.
13. Concurrent participation in another clinical study, unless observational (non-interventional) or in the follow-up phase of an interventional study.
14. Any other condition deemed by the investigator to render the patient ineligible.
18 Years
85 Years
ALL
No
Sponsors
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BeiGene
INDUSTRY
Fujian Medical University Union Hospital
OTHER
Responsible Party
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Locations
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Fujian Medical University Union Hospital
Fuzhou, Fujian, China
Fujian Provincial Hospital Affiliated to Fuzhou University
Fuzhou, Fujian, China
Affiliated Hospital of Putian University
Putian, Fujian, China
Quanzhou First Hospital Affiliated to Fujian Medical University
Quanzhou, Fujian, China
Sanming First Hospital
Sanming, Fujian, China
The First Affi liated Hospital of Xiamen University
Xiamen, Fujian, China
Zhangzhou Affiliated Hospital to Fujian Medical University
Zhangzhou, Fujian, China
Jiangxi Cancer Hospital
Nanchang, Jiangxi, China
Shandong Cancer Hospital
Jinan, Shandong, China
Fudan University Shanghai Cancer Center
Shanghai, Shanghai Municipality, China
Zhejiang Cancer Hospital
Hangzhou, Zhejiang, China
The First Affiliated Hospital of Wenzhou Medical University
Wenzhou, Zhejiang, China
Countries
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Central Contacts
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Facility Contacts
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Shaoxing Zhu, MD
Role: primary
Qingguo Zhu
Role: primary
Guowei Lin
Role: primary
Changde Fu
Role: primary
Dongming Lu
Role: primary
Zhun Wu
Role: primary
Zhiming Zhuang
Role: primary
Xinhua Tu
Role: primary
Jiasheng Bian
Role: primary
Yijun Shen
Role: primary
Jinchao Chen
Role: primary
Hang Huang
Role: primary
Other Identifiers
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HARBOR-II-2025
Identifier Type: -
Identifier Source: org_study_id