Introduction:

The purpose of this study (NCT 03081858) is to report phase 1 outcomes of a novel proliposomal formulation of paclitaxel (TSD-001), specifically designed for intravesical instillation for NMIBC.

Methods:

This is the first in human exposure of TSD-001 (IND129419) in patients with low-intermediate risk NMIBC . The study design is prospective, non-randomized and adaptive, in which two cohorts (n=3, subjects each) received six escalating intravesical dose (range, 10-540 mg TSD-001) exposures every 2 weeks until Dose Limiting Toxicity (DLT, G3-4 AEs) is observed.   Adverse events (AEs) were classified according the NCI CTCAE version 5.0.  Urinary symptom bother was collected using the IPSS and OAB-q instruments.  Bioanalytical measurement of paclitaxel urine and plasma concentration was performed using a validated assay.  Bladder tumor recurrence was assessed by cystoscope and biopsy.

Results:

A total of 5 AEs were reported, all of which were G1 or G2 in intensity and none of which met the criteria for DLT.  There was no change from baseline in the IPSS or OAB-q scores.  No measurable plasma concentrations of paclitaxel (LLQ <5.0 ng/mL) were reported over all doses (10-540 mg).  Urine paclitaxel concentrations demonstrated proportional increase in concentration with increasing dose.  No evidence of clinical recurrence has been identified in the 6 study subjects at a mean follow-up of 12 months.

Conclusion:

NMIBC patients exposed to escalating TSD-001 dose (10-540 mg paclitaxel) until maximum deliverable dose (540 mg) demonstrated no DLT.  Voiding function and bother were unchanged from baseline to completion.  There was no evidence of systemic paclitaxel exposure based on a valid bioanalytical assess.  No evidence of clinical recurrence or progression has been observed at a mean follow-up of 12 months.  TSD-001 delivers high urinary concentrations of paclitaxel with no measurable systemic exposure, and is very well tolerated in NMIBC patients.

Funding: Lipac Oncology, LLC