Abstract PS13-16: Pharmacokinetic evaluation of an oral paclitaxel DHP107 (Liporaxel®) in patients with recurrent or metastatic breast cancer (MBC): Phase II study (OPERA, NCT03326102)
Authors: Rugo Hope S , Pluard Timothy J , Sharma Priyanka , Melisko Michelle , Al-Jazayrly Ghassan , Vidula Neelima , Ji Yan , Weng David , Lim Hyeong-Seok , Yoon Koung Eun , Cho Hyun Ju 
Published: February 2021

Abstract
Background: Paclitaxel is a microtubule stabilizing anticancer therapy used to treat multiple cancers including breast cancer. DHP107 is an oral paclitaxel solubilized in lipid components using DaeHwa-Lipid bAsed Self-Emulsifying Drug delivery system (DH-LASED) technology. It demonstrated comparable efficacy and safety to IV paclitaxel in a phase 3 study for patients with advanced gastric cancer (Ann Oncol 2018) leading to regulatory approval in Korea, and also met the primary endpoint (ORR 54.5%) as first-line therapy (ESMO 2019) in the OPTIMAL Phase II study in patients with HER2 negative metastatic breast cancer (MBC). The confirmatory OPTIMAL Phase III study is ongoing in Asia and Europe. The OPERA Phase II study was designed as multinational, multicenter, randomized, open-label study to establish pharmacokinetic (PK) profile and efficacy of DHP107 in patients with MBC in the U.S. Method: A total of 72 patients with metastatic HER2 negative (HR+/HER2- or triple-negative breast cancer (TNBC)) will be randomized in a 2:1 fashion to receive DHP107 (200mg/m2 orally twice a day on Days 1, 8, and 15 in a 28-day cycle) or IV paclitaxel (80 mg/m2 on Days 1, 8, and 15 in a 28-day cycle) until disease progression or unacceptable toxicity. Tumor assessments are performed every 8 weeks. PK analyses were performed in a subset of patients receiving DHP107. A total of 103 blood samples were collected on Day 1 of Cycle 1 at predose and 1, 2, 3, 4, 6, and 10 hours post dose (before the 2nd dose administration on Day 1), and at predose on Day 8 of Cycle 1. All PK parameters were calculated by non-compartmental analysis using Phoenix WinNonlin version® 8.1. Results: A total of 13 subjects were enrolled in the PK substudy, All 13 patients were female and of Caucasian, non-Hispanic, ethnicity. Median Tmax was 2.17 h (range 1.92-4.08). Mean Cmax and AUC0-10h and their coefficient of variations (CV) were 330 ng/mL (31.1%) and 1233 ng·h/mL (30.3%), respectively (Table 1). The PK parameters of DHP107 were similar to those in a previous Phase I study in Korean cancer patients where Cmax and AUC0-48h were 235 ng/mL (43.9%) and 1348 ng·h/mL (19.7%) (Invest New Drugs 2012).
Conclusion: PK profiles were well characterized from plasma concentrations in 13 Caucasian patients with MBC up to 10 hours after oral 200mg/m2 BID administration. DHP107 was rapidly absorbed and eliminated and inter-individual variability in exposure such as Cmax and AUClast was considered low. Compared to previous phase I PK results in Korean patients, Cmax and AUC parameters were similar after dosing with DHP107, demonstrating no clinically significant differences between Asian and Caucasian patients. Safety and efficacy will be evaluated in the ongoing OPERA and OPTIMAL studies.
Table 1StatisticTmax(h)Cmax(ng/mL)AUClast, 0-10h(ngh/mL)AUCinf(ngh/mL)N13131311Mean(SD)330(103)1233(374)1462(411)CV%31.130.328.1Median[Min-Max]2.17[1.92-4.08]
Citation Format: Hope S Rugo, Timothy J Pluard, Priyanka Sharma, Michelle Melisko, Ghassan Al-Jazayrly, Neelima Vidula, Yan Ji, David Weng, Hyeong-Seok Lim, Koung Eun Yoon, Hyun Ju Cho. Pharmacokinetic evaluation of an oral paclitaxel DHP107 (Liporaxel®) in patients with recurrent or metastatic breast cancer (MBC): Phase II study (OPERA, NCT03326102) [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS13-16.