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

NCT07296705 | Recruiting Phase 2

• 1 other identifier: HARBOR-II-2025
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 12

Brief Summary

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.

Conditions

Muscle Invasive Bladder Cancer (MIBC)

Outcome Measures

Primary Outcomes (1)

• Clinical Complete Response (cCR) Rate

  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

  At the end of Cycle 4 of neoadjuvant therapy (each cycle is 21 days)

Secondary Outcomes (8)

• 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

Study Arms (1)

Experimental group

EXPERIMENTAL

Drug: Zanidatamab; Drug: Tislelizumab; Drug: Cisplatin; Drug: Gemcitabine; Drug: Nab-paclitaxel

Interventions

Zanidatamab DRUG

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.

Experimental group

Tislelizumab DRUG

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.

Experimental group

Cisplatin DRUG

Cisplatin (70 mg/m² administered intravenously every 3 weeks ) for 4 cycles is included in the neoadjuvant chemotherapy regimen for eligible cisplatin-based chemotherapy.

Experimental group

Gemcitabine DRUG

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.

Experimental group

Nab-paclitaxel DRUG

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.

Experimental group

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• 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).

You may not qualify if:

• 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.

Sponsors & Collaborators

• Fujian Medical University Union Hospital: lead
• BeiGene: collaborator

Study Sites (12)

Fujian Medical University Union Hospital

Fuzhou, Fujian, 350001, China

RECRUITING

Fujian Provincial Hospital Affiliated to Fuzhou University

Fuzhou, Fujian, 350001, China

RECRUITING

Affiliated Hospital of Putian University

Putian, Fujian, 351106, China

RECRUITING

Quanzhou First Hospital Affiliated to Fujian Medical University

Quanzhou, Fujian, 362002, China

RECRUITING

Sanming First Hospital

Sanming, Fujian, 365099, China

RECRUITING

The First Affi liated Hospital of Xiamen University

Xiamen, Fujian, 361003, China

RECRUITING

Zhangzhou Affiliated Hospital to Fujian Medical University

Zhangzhou, Fujian, 363000, China

RECRUITING

Jiangxi Cancer Hospital

Nanchang, Jiangxi, 330029, China

RECRUITING

Shandong Cancer Hospital

Jinan, Shandong, 250117, China

RECRUITING

Fudan University Shanghai Cancer Center

Shanghai, Shanghai Municipality, 200032, China

RECRUITING

Zhejiang Cancer Hospital

Hangzhou, Zhejiang, 310005, China

RECRUITING

The First Affiliated Hospital of Wenzhou Medical University

Wenzhou, Zhejiang, 325035, China

RECRUITING

MeSH Terms

Interventions

zanidatamab; tislelizumab; Cisplatin; Gemcitabine; 130-nm albumin-bound paclitaxel

Intervention Hierarchy (Ancestors)

Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring

Central Study Contacts

Shaoxing Zhu, MD

CONTACT

86-18758872716; zsx2005@126.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 26, 2025
• First Posted: December 22, 2025
• Study Start: October 25, 2025
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): December 1, 2029
• Last Updated: December 22, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

CN (12)