Abstract OT3-1-06: A phase 2 single-arm study to evaluate the clinical activity, safety and tolerability of enzalutamide (ENZA) with trastuzumab in patients with advanced human growth factor receptor 2 (HER2)-positive breast cancer

Abstract

Abstract Background Androgen receptor (AR) expression is observed in ∼60% of patients (pts) with HER2+ breast cancer1. In vitro, ENZA inhibits proliferation of AR+/HER2+ cell lines and enhances the activity of trastuzumab. ENZA also inhibits proliferation of trastuzumab resistant HER2 positive cells2. Methods Any amount of AR expression (local or central) is allowed, submission of tissue is mandatory. Patients must have measurable disease per RECIST 1.1, and have received 1 to 4 prior lines of anti-HER2 therapy in the advanced / metastatic setting. Brain imaging is required to exclude patients with CNS metastases. Pts with a seizure history are excluded. Women with metastatic or locally advanced HER2+, AR+, and ER-/PgR- breast cancer will receive daily ENZA (160 mg) continuously and trastuzumab (6 mg/kg) administered every 21 days, until disease progression (NCT02091960). The primary endpoint (EP) is clinical benefit rate (CBR) where benefit is defined as complete or partial response (CR or PR) or stable disease (SD) ≥24 weeks according to RECIST 1.1 criteria. Additional EPs include safety and tolerability, and the relationship between AR expression and ENZA activity. If the CBR is ≥3 in 21 evaluable pts, the sample size will increase to 66 pts. The primary EP will be analyzed in pts with centrally confirmed AR expression (≥10% nuclear staining by IHC), who have received at least one dose of ENZA, and have ≥1 post-baseline tumor assessment. The null hypothesis (H0), that the true CBR is 10%, will be tested against a 1-sided alternative. This Simon’s two-stage design yields 90% power when the true response rate is 25% with a 1-sided type 1 error rate of 5%. Enrollment is expected to continue through 2016.