477P - An international randomized cross-over bio-equivalence study of oral paclitaxel + HM30181 compared with weekly intravenous (IV) paclitaxel in patients with advanced solid tumours

Abstract

BackgroundPaclitaxel has poor oral bioavailability due to excretion by P-glycoprotein (P-gp) on intestinal cells. Oral paclitaxel may reduce IV access, avoid risks of allergic reaction to cremophor, forego steroid premedication, reduce hospital stay, and improve patient convenience. Oraxol (Athenex, USA) is a combination of oral paclitaxel and HM30181, a novel orally active, potent and specific inhibitor of P-gp with minimal or undetectable systemic exposure. We report the results of a bio-equivalence study of Oraxol compared to IV paclitaxel. MethodsAn international randomized crossover pharmacokinetic (PK) study using HM30181 15mg plus oral paclitaxel 205mg/m2 was given on days 1-3 and compared to a single dose of IV paclitaxel (80mg/m2) in patients with advanced solid tumors. PK blood samples were taken days 1-9 for oral paclitaxel and days 1-5 for IV paclitaxel. Results44 patients were randomized. 35 patients were evaluable. The first cohort included 6 patients as a feasibility study. The second cohort included 29 patients and showed:Table477PTableOraxol 205mg/m2 days 1-3Paclitaxel 80mg/m2 IVAUC0-∞ (hr*ng/mL)5001.185589.70Cmax (ng/mL)366.39 (0-24hr), 324.26 (24-48hr), 296.10 (48-72hr)2710.48AUC0-t4797.085425.59GMR (%, 90% CI)89.10 (83.53, 95.03)Intra-subject CV (%)16.05 ConclusionsOraxol (oral paclitaxel + HM30181) given daily for 3 days can show bio-equivalence to single dose of IV paclitaxel 80mg/m2 at 80% power with 90% CI of the GMR within the limits of 80 – 125%. Clinical trial identificationACTRN 12615000894594. Legal entity responsible for the studyAthenex. FundingAthenex. DisclosureC.G.C.A. Jackson: Travel / Accommodation / Expenses: Athenex. N.A. Hung: Shareholder / Stockholder / Stock options, Full / Part-time employment: Zentech. D. Cutler: Shareholder / Stockholder / Stock options, Full / Part-time employment: Athenex. D. Kramer: Full / Part-time employment: Athenex. J. Zhi: Full / Part-time employment: Athenex. W. Chan: Travel / Accommodation / Expenses, Shareholder / Stockholder / Stock options, Full / Part-time employment: Athenex. M.R. Kwan: Leadership role, Travel / Accommodation / Expenses, Full / Part-time employment: Athenex. C. Hung: Research grant / Funding (self), Shareholder / Stockholder / Stock options, Patent: Athenex; Shareholder / Stockholder / Stock options: Zentech. All other authors have declared no conflicts of interest.