A Prospective, Open-label, Single-center Clinical Study Evaluating the Efficacy and Safety of Trastuzumab Combined With BCG Perfusion as an Adjuvant Treatment After TURBT in High-risk/Very High-risk Non-muscle-invasive Bladder Cancer

This is a single-center, prospective, open-label, non-randomized clinical study initiated and conducted by the Department of Urology, Shanghai Changhai Hospital. The Principal Investigators are Professor Zhang Zhensheng and Professor Chen Guanghua. The projected study period is from December 2025 to December 2028. This study aims to evaluate the efficacy and safety of toripalimab (a PD-1 inhibitor) combined with Bacillus Calmette-Guérin (BCG) intravesical instillation as adjuvant therapy following transurethral resection of bladder tumor (TURBT) in patients with high-risk/very high-risk non-muscle-invasive bladder cancer (NMIBC).

Bladder cancer is a common malignancy of the urinary system, with NMIBC accounting for approximately 75% of initial diagnoses. For high-risk patients who are unresponsive to or experience recurrence after BCG therapy, radical cystectomy remains the standard treatment. However, this procedure is associated with high rates of complications, mortality risk, and significantly negative impacts on quality of life. Therefore, exploring novel combination strategies that effectively reduce recurrence while preserving the bladder is of great clinical importance. This study is based on the successful application of immune checkpoint inhibitors in advanced urothelial carcinoma and recent Phase III trials (e.g., the CREST study) demonstrating the efficacy and safety of combining PD-1/PD-L1 inhibitors with BCG in treatment-naïve high-risk NMIBC. It seeks to investigate the potential of the domestic PD-1 inhibitor toripalimab in combination with standard BCG instillation.

The study plans to enroll 31 patients with histologically confirmed high-risk/very high-risk NMIBC who have not previously received immune checkpoint inhibitors or BCG therapy. All enrolled patients will first receive a single instillation of gemcitabine (2000mg), followed by the combination therapy phase: toripalimab (240mg, intravenous infusion, every 3 weeks for 8 cycles) combined with BCG intravesical instillation (induction phase for 6 weeks, maintenance phases at months 3 and 6). The primary efficacy endpoint is the pathological complete response (CR) rate at approximately 6 months after treatment initiation. Secondary efficacy endpoints include duration of CR, 6-month and 2-year event-free survival (EFS) rates, 1-year and 2-year cancer-specific survival (CSS) rates, time to radical cystectomy, and overall survival (OS). Safety endpoints encompass the incidence and severity of adverse events (AEs) and serious adverse events (SAEs).

Statistical analyses will be based on the Full Analysis Set (FAS) and Per-Protocol Set (PPS). The sample size calculation for the primary endpoint (6-month CR rate) is based on historical data assumptions, employing a one-sided test. Safety analyses will include all patients who received at least one dose of study treatment. This study will strictly adhere to the principles of the Declaration of Helsinki, Chinese Good Clinical Practice (GCP) guidelines, and relevant regulations. The study protocol has been submitted for review and approval by the Institutional Review Board (IRB)/Ethics Committee. Written informed consent will be obtained from all patients prior to participation. This study aims to provide a new and potentially more effective bladder-preserving treatment option for patients with high-risk/very high-risk NMIBC and to evaluate the safety profile of this combination regimen.