A phase I first-in-human clinical trial with PLZ4-coated paclitaxel-loaded micelles (PPM) in therapy-resistant non-muscle-invasive bladder cancer (NMIBC).

• DOI: 10.1200/jco.2025.43.5_suppl.806
• Publication Date: 2025-02-18T14:32:56Z
• Authors: Chong-xian Pan; Juan Garisto; Lori Lerner; Matthew Mossanen; Marc Dall'era; Hizra Farrukh; Colleen Hynes; Mamta Parikh; Primo N Lara; Urvashi Bhardwaj; Ai-Hong Ma; Joyce S. Lee; Yuanpei Li; Tzu-yin Lin; Yanxiao Jiao; Junwei Zhao; Ruiwu Liu; Kit S Lam

806 Background: Approximately 75% of patients with non-muscle invasive bladder cancer (NMIBC) treated transurethral resection (TUR) followed by intravesical Bacillus Calmette-Guérin (BCG) experience recurrence. When BCG-unresponsive, most continue to have recurrences even newly approved therapies and nearly 30% progress stages. We developed a first-in-class cancer-specific nanotherapeutic, PPM, which is administered intravesically. Our preclinical data has demonstrated PPM can selectively target cells deliver paclitaxel payload into these following or intravenous administration. Methods: This 3+3 first-in-human dose escalation trial. Eligible must pathologically confirmed NMIBC, be unresponsive BCG therapy (with without cytotoxic chemotherapy), possess adequate vital organ function, consent cystoscopy TUR for response evaluation. via instillation once weekly six weeks. The trial features three levels, doses 25 mg, 50 75 mg. primary endpoints include safety the recommended Phase II dose; secondary encompass rate, duration response, systemic drug absorption, molecular correlative studies. Patients will at 3 month intervals 2 years until disease progression. Results: To date, NMIBC completed total 18 treatments first level any PPM-related adverse events: one patient was mitomycin therapy, while other two had BCG-unresponsive disease. Two out achieved ongoing complete remission over nine months, respectively. third persistent disease, but no progression noted. Enrollment Dose Level currently open. Conclusions: promising clinical activity toxicity in NMIBC. Data levels presented meeting (ClinicalTrials.gov identifier: NCT05519241). Clinical information: NCT05519241 .