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.
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.
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.
NCT05519241.
Bladder cancer is a common disease, especially among Veterans. For many patients, cancer stays on the inner surface layer of the bladder (non-muscle-invasive). The standard treatment is resection plus an immunotherapy called Bacille Calmette-Guérin (BCG). However, cancer often recurs in many patients. If it keeps returning, doctors may have to remove the entire bladder, which is a major surgery and associated with significant morbidities. We test a new “smart” medicine called PPM. PPM is made of tiny particles, less than one-thousandth the diameter of a hair, that carry a cancer-killing drug called paclitaxel. These particles have a special “sensor” named PLZ4 on the surface and work like precision-guided munitions. After instillation of PPM into the bladder cavity, PLZ4 can specifically target and deliver PPM together with the paclitaxel drug load into cancer cells while sparing the healthy parts of the bladder alone. This study assesses the toxicity profile of PPM and determines the appropriate dose for future clinical trials. Additionally, it evaluates the efficacy of PPM in patients with non-muscle-invasive bladder cancer who have not responded to BCG treatment.
Nanomedicine (London, England). 2026 Jul 08 [Epub ahead of print]
Chong-Xian Pan, Matthew Mossanen, Jeffrey L Ellis, Ai-Hong Ma, Chun Yang, Hizra Farrukh, Yanxiao Jiao, Urvashi Bhardwaj, Joyce S Lee, Primo N Lara, Colleen Hynes, Tzu-Yin Lin, Yuanpei Li, Lori Lerner, Mark A Preston, Adam Kibel, Marc Dall'Era, Kit S Lam
Department of Medicine, VA Boston Healthcare System, Boston, MA, USA., Department of Urology, Mass General Brigham, Boston, MA, USA., University of California Davis, Sacrament, CA, USA.