Abstract OT1-05-02: A phase II study to evaluate the efficacy, safety and pharmacokinetics of DHP107 (Liporaxel®, oral paclitaxel) compared to IV paclitaxel in patients with recurrent or metastatic breast cancer: OPERA (NCT03326102)
Authors: Pluard Timothy J , Sharma Priyanka , Melisko Michelle E. , Vidula Neelima , Weng David E , Skelton Jane D , Yoon Koung Eun , Cho Hyun Ju , Rugo Hope S 
Published: March 2020

Abstract
Background: Paclitaxel is a commonly used anticancer drug worldwide for various cancers including breast cancer. DHP107 is a novel oral formulation of lipid based components and paclitaxel. DHP107 showed comparable efficacy and safety to IV paclitaxel in a phase 3 study for patients with advanced gastric cancer (DREAM study, Ann Oncol 2018). DHP107, Liporaxel® was approved as the first oral paclitaxel in 2016 for gastric cancer in Korea. Currently the OPTIMAL Phase III study is ongoing in Korea and China to evaluate the efficacy of Liporaxel® as first-line therapy in recurrent or metastatic breast cancer. The OPERA Phase II study aims to evaluate the efficacy, safety and pharmacokinetics of DHP107 compared to IV Paclitaxel in non-Asian American patients in U.S. with recurrent or metastatic breast cancer. Trial Design: The OPERA study is a multi-center, randomized, open-label phase II trial enrolling HER2 negative (HR+/HER2- or triple-negative breast cancer (TNBC)) recurrent or metastatic breast cancer patients. Seventy two eligible subjects are being randomized in a 2:1 fashion to receive DHP107(200mg/m2 orally twice daily) or IV paclitaxel 80 mg/m2 on Days 1, 8, and 15 in a 28-day cycle) until disease progression, intolerable toxicity, or withdrawal from this study. Stratification factors include ‘TNBC vs. non-TNBC’ and ‘disease-free interval (DFI) ≤ 12 months vs. DFI &gt; 12 months’. A subset of the first 12 eligible subjects receiving DHP107, blood samples for PK analysis are collected on Day 1 of Cycle 1 at predose(0) and 1, 2, 3, 4, 6, and 10 hours post dose (before the 2nd dose administration on Day 1), and on Day 8 of Cycle 1 at predose (before the 1st dose on Day 8). Tumor assessments are performed every 8 weeks ± 7 days from C1D1 until disease progression or initiation of subsequent chemotherapy. Eligibility Criteria: Subjects must have confirmed HER2 negative breast cancer by immunohistochemistry (IHC) or in situ hybridization (ISH). HR positive (&gt;1%) or negative patients are eligible. Subjects can have received up to 3 lines of therapy for advanced disease, without prior exposure to taxane in the advanced stage setting. Subjects must have performance status of ≤2 on the Eastern Cooperative Oncology Group (ECOG) scale and measurable disease according to the Response Evaluation Criteria in Solid Tumors Version 1.1 (by RECIST version 1.1). Subjects with treated CNS metastases that are documented to be stable by CT or MRI imaging ≥4 weeks after completion of radiation and who do not require systemic corticosteroids are eligible. Subjects with neuropathy grade ≥2 based on CTCAE v4.03 are excluded. Specific Aims: The primary endpoint is objective response rate (ORR). Secondary endpoints include progression free survival (PFS), overall survival (OS), time-to-treatment failure (TTF), duration of response (DOR), disease control rate (DCR), quality-of-life (QoL) and safety. Statistical Design: Seventy two subjects are being enrolled, with an estimated drop-out rate of 10%. This sample size is sufficient to ensure that the lower one-sided 95% confidence limit for the true difference in response rates extends no more than 20% from the observed difference; this calculation assumes that the observed ORR is 60% in both groups. Target Accrual: The first subject was enrolled in July 2018 and recruitment is ongoing. Enrollment of 72 evaluable subjects is expected to complete in Q2 2020.
Citation Format: Timothy J Pluard, Priyanka Sharma, Michelle E. Melisko, Neelima Vidula, David E Weng, Jane D Skelton, Koung Eun Yoon, Hyun Ju Cho, Hope S Rugo. A phase II study to evaluate the efficacy, safety and pharmacokinetics of DHP107 (Liporaxel®, oral paclitaxel) compared to IV paclitaxel in patients with recurrent or metastatic breast cancer: OPERA (NCT03326102) [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr OT1-05-02.