A first-in-human trial of intravesical BH011, a novel docetaxel formulation, in patients with high risk non-muscle invasive bladder cancer (HR-NMIBC) after BCG failure: Results from a phase 1 study.

e16605 Background: 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. Treatment options are limited for patients (pts) with HR-NMIBC after BCG failure. This study evaluates the safety, pharmacokinetics (PK), and efficacy of BH011 in pts with HR NMIBC after BCG failure. Methods: This open-label, single arm phase I study enrolled BCG failure (including refractory, recurrence, non-responsive, and intolerant) HR-NMIBC pts. The papillary tumors should be removed all visible lesions by transurethral resection of bladder tumor (TURBT). Dose escalation phase aims to identify the Phase II recommended dose (RP2D) of intravesical BH011 at the following dose levels: 7.5 mg, 12.5 mg, and 17.5mg. 17.5mg is used as the starting dose. Within 2-8 weeks after TURBT, eligible pts receive BH011 intravesical therapy on day 1, once a week for 6 weeks during the induction treatment period and once a month for 12 months during the maintenance treatment period. The primary end point is safety (adverse events, including MTD, dose-limiting toxicity(DLT) and RP2D). Secondary end points include PK, Recurrence-Free Survival (RFS), RFS rate, Progression-Free Survival (PFS) , PFS rate, Complete Response (CR) rate and duration of CR. Follow-up disease surveillance (cystoscopy, urine cytology) will be every 3 months to end of Year 2. Imaging is performed annually. Results: In total, 6 patients received BH011 17.5mg treatment; of which 1 patient was CIS. BH011 was well tolerated with no DLTs, and 17.5mg was identified as the RP2D. No BH011-related serious adverse events (AEs) occurred. All TRAEs were grade ≤2 [CTCAE v5.0], and common AEs were urinary tract infections, hematuria, and proteinuria. All patients completed their dosing as required by the protocol, and there were no delays or interruptions in dosing or dose adjustments. Pharmacokinetic evaluation showed that after intravesical 17.5 mg BH011 in six pts, the plasma C max was 0.37 ng/mL, the AUC 0-last was 2.77 ng·h/mL, the AUC 0-inf was 3.15 ng·h/mL, the elimination half-life (t 1/2 ) was 5.71 hs, and the T max was 1.29 hs. The results showed that BH011 intravesical administration was permeable in the bladder mucosa, but systemic absorption was minimal and the incidence and severity of systemic adverse effects were mild. 100% (6/6) pts had CR at 3 month; of which 3 pts remained in CR at 12 months. To date, the PFS rate was 100%. Conclusions: These results demonstrate the safety, tolerability and therapeutic potential of intravesical BH011 in patients with HR-NMIBC after BCG failures. The phase 2 clinical study is ongoing. Clinical trial information: NCT06732531 .