1511 - A pilot study of oral paclitaxel (ORAXOL) in subjects with cutaneous angiosarcomas (KX-ORAX-010)

Background

Angiosarcomas (AS) are rare and aggressive tumors of endothelial cell origin. About half of patients present with a primary cutaneous lesion, most commonly over the scalp. Intravenous (IV) weekly paclitaxel (Pac) is the current accepted standard-of-care in inoperable or progressive disease. Median PFS is 3.8 months. IV Pac is associated with dose-limited toxicities including peripheral neuropathy, development of infusional reactions and anaphylaxis, in part due to the Cremophor EL formulation vehicle. Pac is a P-glycoprotein (P-gp) substrate. Pac is a substrate for the Pgp pump in the intestinal cells which leads to efflux of Pac back into the intestinal lumen, thereby making the drug nonbioavailable when taken orally. ORAXOL is a combination product of 2 separate drugs; oral Pac and a novel Pglycoprotein (Pgp) inhibitor, HM30181 methanesulfonate monohydrate (HM30181A). This allows for intestinal absorption and systemic exposure of Pac. ORAXOL has been studied in bioavailability and bioequivalence studies confirming its safety profile. A multi-center phase III study comparing ORAXOL and IV Pac in women with metastatic breast cancer is on-going. We are currently recruiting patients on a multi-center pilot study to determine the efficacy of ORAXOL in cutaneous AS.

Trial design

This is a multi-center, international, open-label, pilot study to evaluate the activity, safety, and tolerability of ORAXOL in subjects with cutaneous AS who have not been treated previously with taxanes. ORAXOL (15mg oral HM30181A & 205mg/m² oral Pac) will be administered once daily for 3 consecutive days every week from Weeks 1 through 25; HM30181A is administered 1 hour before oral Pac on dosing days. Subjects who do not have disease progression at the end of treatment period are eligible to continue ORAXOL in the treatment extension phase. Primary objective is to determine the response rate (RR) within 6 months of initiation of treatment. Secondary objectives include (i) safety and tolerability, (ii) PFS and (iii) OS, (iv) duration of- and (v) time to-best response. Up to 25 evaluable subjects across 4 study sites will be enrolled in this study. The first patient has started dosing in December 2018.

Clinical trial identification

NCT03544567.

Editorial acknowledgement

Legal entity responsible for the study

Athenex Inc.

Funding

Athenex Inc.

Disclosure

M.R. Kwan: Leadership role, Shareholder / Stockholder / Stock options, Full / Part-time employment: Athenex Inc. D. Cutler: Leadership role, Shareholder / Stockholder / Stock options, Full / Part-time employment: Athenex Inc. D. Kramer: Leadership role, Shareholder / Stockholder / Stock options, Full / Part-time employment: Athenex Inc. W. Chan: Leadership role, Shareholder / Stockholder / Stock options, Full / Part-time employment: Athenex Inc. All other authors have declared no conflicts of interest.