PLZ4-coated paclitaxel micelles (PPM) show early safety and 67% complete remission in BCG-unresponsive NMIBC

Patients with non-muscle-invasive bladder cancer (NMIBC) refractory to Bacillus Calmette-Guérin (BCG) therapy face frequent recurrence and limited long-term benefits from existing treatments. This highlights a critical need for novel, targeted intravesical strategies. Paclitaxel is a potent cytotoxic agent, but its systemic toxicity and poor bladder penetration limit its direct use. A bladder cancer-specific peptide, PLZ4, offers a promising avenue for targeted drug delivery, enhancing paclitaxel's efficacy while minimizing off-target effects and improving local drug concentrations.

This first-in-human, single-arm Phase I trial enrolled up to 29 patients with BCG-unresponsive or intolerant NMIBC. Participants receive intravesical PLZ4-coated paclitaxel-loaded micelles (PPM) once weekly for 6 weeks. Doses of paclitaxel were escalated at 25 mg (0.5 mg/mL), 50 mg (1.0 mg/mL), or 75 mg (1.5 mg/mL) in normal saline. Primary endpoints focused on safety and toxicity, assessed using CTCAE v5.0, and determining the recommended Phase II dose (RP2D). Efficacy was a secondary endpoint, evaluated via cystoscopy and urine cytology at 6 weeks post-intervention.

Preliminary results from the first 3 enrolled patients, all with BCG-unresponsive NMIBC, who completed treatment at the initial 25 mg dose level, showed promising safety and efficacy. No drug-related adverse events were observed across these initial participants. Importantly, a significant clinical response was noted:

Two out of these first three patients (67%) achieved complete remission at the 6-week post-intervention assessment. This early data suggests that intravesical PPM is well-tolerated and can induce substantial anti-tumor activity in a challenging patient population. The study is currently open for further enrollment and dose escalation.