This prospective, multicenter, open-label phase II study will evaluate a response-guided bladder-preservation strategy in patients with HER2-expressing muscle-invasive bladder cancer. Participants will receive maximal transurethral resection of the bladder tumor, trastuzumab rezetecan plus adebrelimab, and concurrent bladder radiotherapy. Treatment response will be assessed by cystoscopic biopsy or diagnostic transurethral resection at 8 weeks (±2 weeks) after radiotherapy. Participants with a pathological stage of T1 or lower may continue bladder-preserving management, whereas radical cystectomy will be recommended for participants with disease above T1. The primary outcome is the major pathological response rate.
Age ≥18 years, male or female; able to provide written informed consent; willing and able to comply with all protocol-required examinations and follow-up.
Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
Histologically confirmed muscle-invasive urothelial carcinoma of the bladder. Minor squamous, glandular, or other mixed differentiation is permitted. Patients with pure non-urothelial carcinoma may be enrolled at the investigator's discretion.
Clinical stage cT2-T4a, N0, M0, based on pelvic/abdominal imaging with or without chest imaging.
1. Distant metastasis (M1), clearly uncontrollable extra-regional metastatic disease, or an upper urinary tract tumor requiring priority treatment.
Single group
Trastuzumab Rezetecan
DrugTrastuzumab rezetecan will be administered intravenously at a dose of 4.8 mg/kg every 3 weeks for 4 cycles.
Adebrelimab
DrugAdebrelimab will be administered intravenously at a dose of 1200 mg every 3 weeks for 4 cycles.
Concurrent Bladder Radiotherapy
RadiationBladder radiotherapy will be delivered to a total dose of 60-64 Gy in 30-32 fractions, at 2.0 Gy per fraction, once daily, 5 fractions per week, over approximately 6 weeks. Radiotherapy will be initiated concurrently with systemic therapy.
Transurethral Resection of Bladder Tumor
Procedure/SurgeryParticipants will undergo maximal transurethral resection of the bladder tumor before combined treatment. Cystoscopic biopsy or diagnostic TURBT will be performed at 8 weeks (±2 weeks) after radiotherapy to assess pathological response.
Major Pathological Response Rate
The percentage of participants whose pathological stage is downstaged to non-muscle-invasive disease (ypT0, ypTa, ypTis, or ypT1), as confirmed by cystoscopic biopsy or diagnostic transurethral resection of the bladder tumor.
Event-Free Survival (EFS)
Time from treatment initiation to the first occurrence of disease progression precluding surgery, local or distant recurrence, or death from any cause.
Overall Survival (OS)
Time from signing informed consent to death from any cause.
Bladder Preservation Rate
Percentage of participants who retain their native bladder without undergoing radical cystectomy during the follow-up period.
1-Year and 2-Year Bladder Event-Free Survival Rates
The percentages of participants who retain their native bladder without muscle-invasive recurrence, lymph node or distant metastasis, salvage radical cystectomy, or bladder cancer-related death.
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Tongji Hospital
Lead sponsor
Jiangsu Hengrui Pharmaceutical Co., Ltd.
Collaborator
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