Background: Poziotinib is a novel, oral, irreversible pan-HER inhibitor that has shown promising clinical activity in Phase 1 studies of patients (pts) with advance HER2 positive breast cancer who have failed at least 2 prior lines of HER2-directed therapy. A Phase 2 study of poziotinib was initiated in Korea in March 2015 in pts with HER2+ metastatic breast cancer. This phase 2 study is designed to seek accelerated approval for poziotinib for the treatment of metastatic breast cancer in Korea.

Trial Design: Prospective Phase 2, open-label, single-arm, multi-center study in pts with recurrent, Stage IV breast cancer with HER2-overexpression who had received at least 2 prior HER2-directed regimens

Eligibility Criteria: Histologically confirmed breast cancer patients, at least 19 years of age, with confirmed HER2 positive evaluable tumors (per RECIST, 1.1) who have adequate hematologic, renal, and hepatic function and have failed at least two HER2-directed regimens that included a taxane-containing anticancer chemotherapy, with a life expectancy of at least 12 weeks.

Specific Aims: The Primary Efficacy Endpoint of the study was Progression-Free Survival (PFS). The Secondary Efficacy Endpoints included: PFS rate at 12 weeks post-dose; Objective Response Rate (ORR) including Complete Response (CR) and Partial Response (PR) rates; Disease Control Rate (DCR) including CR, PR, and Stable Disease (SD); Duration of Disease Control; Overall Survival (OS); Time to Progression (TTP); Time to Objective Response and Duration of Objective Response. The Exploratory Endpoints included: Population Pharmacokinetic (PK) Profile and Exploratory Genomic and Biomarker Analyses.

Statistical Methods: In the randomized, multicenter, 2-arm, open-label study of trastuzumab emtansine (TH3RESA18), the median PFS was shown to be 3.3 months in subjects with optimal treatment per Investigator's Choice. This ongoing study with poziotinib expects a median PFS of 4.5 months based on data from a previous Phase 1 study of poziotinib (NOV120101). Based on the following assumptions, a 5% one-sided significance level, and 80% power, and 2 months of accrual and 12 months of follow-up, 66 subjects will be required. Accounting for a 10% drop-out rate, a total of 74 subjects will be recruited into this ongoing Phase 2 study.

Present Accrual and Target Accrual: 17 patients enrolled as of May 20, 2015 with a total target enrollment of 74 patients

Contact information: Identifier: NCT02418689.

Citation Format: Park Y-H, Jung KH, Sohn JH, Lee KS, Lee KH, Kim J-H, Kim J-Y, Jung J, Han H, Park W-Y, Im S-A. A prospective, open-label, single-arm, multi-center, phase II exploratory study to evaluate the efficacy and safety of poziotinib (NOV120101) in patients with HER2-positive metastatic breast cancer who have received at least two prior HER2-directed regimens. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr OT3-01-10.