Results of BH011 after intravesical administration in patients with CIS and/or papillary non-muscle invasive bladder cancer (NMIBC) after BCG failure: Interim results from a phase I/II clinical trial.

4607 Background: Treatment options are limited for patients (pts) with high risk NMIBC (HR NMIBC) after BCG failure. BH011 is a novel docetaxel formulation for intravesical administration that significantly increased the concentration of free docetaxel and bladder tissue permeability compared to TAXOTERE, which may result in a more efficient and effective tumor response. BH011 is administered intravesically to providing durable efficacy in high-risk NMIBC while avoiding systemic toxicities. This phase I/II study evaluates the safety, preliminary efficacy of intravesical BH011 in pts with HR NMIBC after BCG failure. Methods: This phase I/II study enrolled BCG failure (including refractory, recurrence, non-responsive, and intolerant) HR NMIBC pts. The papillary tumors should be removed all visible lesions by TURBT. The purpose of this study was to assess the preliminary efficacy under 17.5mg. Within 2-8 weeks after TURBT, eligible pts receive BH011 on day 1, once a week for 6 weeks during the induction treatment and once a month for 12 months during the maintenance treatment. The primary efficacy endpoint was 3 month Complete Response Rate (CRR). Results: To date, 25 pts have been treated with 17.5 mg of BH011, including 7 pts with CIS (±Ta/Ta) and 18 pts with papillary tumors alone (high-grade Ta or T1). All patients had been previously treated with BCG and failed. BH011 was well tolerated by all pts. All treatment-related adverse events (TRAE) were grade ≤ 2 and there were no TRAEs leading to discontinuation. Common TRAEs include urinary tract infection, glucosuria, proteinuria, urinary frequency, haematuria, cholesterol high, creatinine increased, and anaemia. A total of 24 evaluable pts were included in the efficacy analysis, which showed that pts had a CRR of 96% at 3 months and 71% at 12 months. RFS and PFS were analysed using the Kaplan-Meier method, and the 12-month RFS rate was 70%, with a median RFS of 20.21 months and a PFS rate of 100%. Six evaluable pts with CIS (±Ta/Ta) were analysed and the CRR was 100% (6/6) at 3 months and 83% (5/6) at 12 months. Analysis of the different pathology type subgroups and BCG failure type subgroups showed that the clinical efficacy of BH011 was independent of pathology type and BCG failure type (P＞0.05). Conclusions: Interim results show that intravesical BH011 is well tolerated and that it has strong significant and durable clinical efficacy in patients with HR NMIBC after BCG failure, particularly in pts with CIS (CRR = 100%). BH011 has the potential to have a transformative effect on the treatment landscape of NMIBC. Clinical trial information: NCT06732531 . Efficacy of BH011. Month 3 6 12 CR rate in all Pts, % 96 79 71 CR rate in CIS (±Ta/T1), % 100 83 83 RFS rate in all Pts, % ( 95%CI) 96 (88, 100) 79 (61, 97) 70 (45, 95) DOR rate in all Pts, % ( 95%CI) 96 (87, 100) 78 (59, 97) 68 (33, 100)