MP72-01 PHASE 1 OUTCOMES OF A NOVEL THIRD GENERATION LIPOSOMAL PACLITAXEL FORMULATION (TSD-001) IN LOW-INTERMEDIATE RISK NON-MUSCLE INVASIVE BLADDER CANCER (NMIBC) PATIENTS

You have accessJournal of UrologyBladder Cancer: Non-invasive III (MP72)1 Apr 2020MP72-01 PHASE 1 OUTCOMES OF A NOVEL THIRD GENERATION LIPOSOMAL PACLITAXEL FORMULATION (TSD-001) IN LOW-INTERMEDIATE RISK NON-MUSCLE INVASIVE BLADDER CANCER (NMIBC) PATIENTS Michael Oefelein*, Danny Huynh, Rian Dickstein, and Karl Bean Michael Oefelein*Michael Oefelein* More articles by this author , Danny HuynhDanny Huynh More articles by this author , Rian DicksteinRian Dickstein More articles by this author , and Karl BeanKarl Bean More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000000952.01AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: 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 NMIBC intravesical instillation. Paclitaxel is a first-line agent for a variety of carcinomas, and is active against metastatic urothelial cancer. Proliposomal paclitaxel is highly active against bladder cancer cells (IC50 T24 cells=4.7 ng/mL TSD-001 vs 1000 ng/mL MMC), demonstrates targeted lethality, with deep penetration into detrusor and intravesical persistence up to 72 hours. METHODS: This is the first in human exposure of TSD-001 (IND129419) in patients after TURBT documented 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 8 AEs were reported, all of which were G1 (n=7) or G2 (n=1) in intensity and none of which met the criteria for DLT. There was no change from baseline in the IPSS (13 vs 15) or OAB-q scores (89 vs 95). 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 TCCa clinical recurrence has been identified in the 6 study subjects at a mean follow-up of 12 months. CONCLUSIONS: 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 TCCa recurrence 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. Source of Funding: Lipac Oncology, LLC © 2020 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 203Issue Supplement 4April 2020Page: e1073-e1073 Advertisement Copyright & Permissions© 2020 by American Urological Association Education and Research, Inc.MetricsAuthor Information Michael Oefelein* More articles by this author Danny Huynh More articles by this author Rian Dickstein More articles by this author Karl Bean More articles by this author Expand All Advertisement PDF downloadLoading ...