Introduction:
TSD-001 (LiPax) is a pro-liposomal paclitaxel formulation specifically designed for intra-cavitary administration. The lead program for this formulation is intermediate risk NMIBC (IND129419)(NCT03081858)
Methods:
This is an open-label trial of NMIBC patients with Ta, low grade disease (n=15). The first 6 patients (Phase1) had TURBT followed by biweekly intravesical dose-escalation (10-540 mg) TSD-001. The remaining patients (Phase 2a) were treated weekly for 6-8 weeks to assess the Marker Lesion Response Rate (MLRR). Paclitaxel concentrations were measured in plasma and urine. Urinary HR-QOL and adverse events were collected.
Results:
Extensively pre-treated and highly recurrent intermediate risk NMIBC were treated with 360 mg TSD-001 (Lipax) weekly for 6-8 weeks. The MLRR was 56%. The 1-year RFS for the first 6 patients is 83%.
Persistence of paclitaxel in the voided urine above the inhibitory conentration-50 levels (IC-50) of T-24 bladder cancer cells was demonstrated up to 72 hours after intravesical instillation Figure 1).
Intravesical instillation of LiPax has demonstrated excellent safety and tolerability. Specifically, no related adverse events of grade 3 or 4 were observed, and urinary health related quality of life, as measured by patient reported outcomes IPSS, OAB-q), did not change before, during or after intravesical exposure to LiPax (Figure 2).
Conclusion:
In patients with highly recurrent, low grade, Ta NMIBC, intravesical administration of LiPax demonstrated no dose limiting toxcicity. Urinary HR-QOL remained unchanged after up to 8 intravesical instillations. Persistence of paclitaxel in the voided urine at therapeutic concentrations up to 72 hours after instillation were observed. The MLRR in recurrent patients with history of pretreatment was 56%. The 1-year RFS after TURBT and induction LiPax (x6) is 83%. Together these results support advancing LiPax into phase 2b clinical development.
Funding: Lipac Oncology
Image(s) (click to enlarge):
PHASE 2 MARKER LESION RESULTS FOR PROLIPOSOMAL PACLITAXEL (LIPAX) IN INTERMEDIATE RISK NMIBC
Category
Bladder Cancer > Non-Muscle Invasive Bladder Cancer
Description
Poster #24
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Presented By: Michael G. Oefelein
Authors:
Neal Shore
David Y Josephson
Karl Bean
Danny Huynh
Rian Dickstein