Phase (Ph) 1 study of oral seviteronel (VT-464), a dual CYP17-Lyase (L) inhibitor and androgen receptor (AR) antagonist, in patients (pts) with advanced AR+ triple negative (TNBC) or estrogen receptor (ER)+ breast cancer (BC).

Abstract

1088Background: Seviteronel (Sevi), a CYP17-L inhibitor (reduces androgen and estrogen biosynthesis) and AR antagonist, has activity in castration resistant prostate cancer (CRPC) at a dose of 750 mg nightly. Sevi potently and dose-dependently inhibits the growth of ER(+)/AR(+) tamoxifen-resistant (TAMR) MCF7 and ER(-)/AR(+) MDA-MB-453 cells. In a TAMR xenograft BC model, Sevi decreases tumor growth > enzalutamide, an AR antagonist (Ellison et al. SABCS 2015). Approximately 80% of BCs, including a subset of TNBC that expresses AR, are potential targets for Sevi based on its mechanism of action (MOA). The primary objective of this Ph 1 study is to establish the recommended Ph 2 dose (RP2D) in women with BC (NCT02580448). Methods: Eligible pts have AR(+) TNBC or ER(+)/HER2-normal metastatic BC. ER(+) pts must have had ≥ 1 prior line of endocrine therapy; no limit to prior treatment for TNBC. Sevi start dose was 750 mg, administered nightly with dinner (28 d cycle) (n = 6/cohort). AR(+) status was confirmed ...