Phase I first-in-human dose-escalation trial of a bladder cancer-specific nanoparticle in non-muscle-invasive bladder cancer

OBJECTIVES: Non-muscle-invasive bladder cancer (NMIBC) refractory to Bacillus Calmette-Guérin (BCG) treatment recurs frequently, even with recent approved therapies. We developed a novel, solvent-free, cancer-specific nanoparticle, PLZ4-coated paclitaxel-loaded micelles (PPM), designed for targeted drug delivery and enhanced efficacy. PLZ4 is a bladder cancer-specific peptide that is decorated on the micelle surface of PPM for cancer-specific drug delivery, while paclitaxel is encapsulated for cytotoxic activity. This first-in-human, single-arm Phase I trial aims to evaluate safety, toxicity, and establish the recommended Phase II dose (RP2D) of intravesical PPM in patients with BCG-unresponsive or intolerant NMIBC. METHODS: Eligible patients have BCG-unresponsive NMIBC with adequate organ function and performance status. Up to 29 participants will be enrolled in the dose-escalation and expansion cohorts. PPM is administered intravesically once weekly for 6 weeks at paclitaxel doses of 25 mg (0.5 mg/mL), 50 mg (1.0 mg/mL), or 75 mg (1.5 mg/mL) in normal 0.9% saline, regardless of patient body size or weight. Primary endpoints are safety and determination of RP2D, using the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE v5.0) for toxicity assessment. Efficacy is evaluated via cystoscopy and urine cytology at 6 weeks post-intervention. PRELIMINARY RESULTS: Three BCG-unresponsive patients have been enrolled and finished treatment at the first dose level. No drug-related adverse event was observed. Two out of these first three patients achieved complete remission. The study is still open for enrollment. CLINICAL TRIAL REGISTRATION: NCT05519241.