Abstract OT1-02-10: A phase 2 study of poziotinib in patients with HER2-positive metastatic breast cancer (MBC) who have received prior HER2 regimens for MBC

Abstract

Abstract Background: Poziotinib is a novel, oral, quinazoline-based pan-HER inhibitor that irreversibly blocks signaling through the epidermal growth factor receptor (EGFR) family of tyrosine-kinase receptors, including EGFR (HER1/ErbB1/EGFR), HER2 (ErbB2), and HER4 (ErbB4), as well as HER receptor mutations. This, in turn, leads to inhibition of the proliferation of tumor cells that overexpress these receptors. It is well established that breast cancers are associated with a mutation in, or overexpression of, members of the EGFR receptor family. The primary objective of this Phase 2 study is to evaluate the Objective Response Rate (ORR) of poziotinib in patients with human epidermal growth factor receptor 2 (HER2)-positive MBC. The secondary efficacy variables are Progression-Free Survival (PFS), Disease Control Rate (DCR), Overall Survival (OS), and Time to Progression (TTP). Trial Design: This is a Phase 2, open-label, multicenter study to evaluate the efficacy, safety and tolerability of poziotinib in patients with HER2-positive MBC who have received at least 2 prior HER2- directed treatment regimens. Each treatment cycle is 21 days in duration. During each cycle, eligible patients receive 24 mg of poziotinib orally (as three 8-mg tablets) once daily for 14 days, followed by a 7 day treatment-free period. Eligibility Criteria: Eligible patients are at least 18 years of age, have confirmed HER2 overexpression, adequate hematologic, renal and hepatic function, and have received at least 2 prior HER2-directed therapy regimens, including trastuzumab and trastuzumab emtansine (TDM-1). Patients are excluded if they have prior exposure to poziotinib, a history of congestive heart failure, left ventricular ejection fraction <50%, unable to take oral medications, or have conditions that cause malabsorption. A 30 day wash out period from previous chemotherapeutic or radiation therapies is required. Statistical Methods: The purpose of this study is to evaluate the efficacy of poziotinib compared to the efficacy of other standard HER2-positive breast cancer treatments as reported in the literature. The ORR will be analyzed descriptively along with the 95% CI. The secondary efficacy variables will be analyzed descriptively. Target Accrual: Approximately 70 patients. Enrollment began February 2016. Contact Information: For more information or to refer a patient, email: spi-poz-201@sppirx.com or fax: 1-949-398-9711. Citation Format: Lathrop K, Lucas J, Vacirca JL, Bhat G, Choi MR, Naughton M. A phase 2 study of poziotinib in patients with HER2-positive metastatic breast cancer (MBC) who have received prior HER2 regimens for MBC [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr OT1-02-10.