Abstract CT058: A phase 2 open-label study to evaluate the efficacy and safety of VT-464 in patients with androgen receptor positive triple-negative breast cancer patients, and men with ER positive breast cancer

Background: The androgen receptor (AR) is expressed in 20-30% of patients with triple negative breast cancer (TNBC). In phase 2 trials androgen blockade with bicalutamide demonstrated a clinical benefit rate (CBR = Partial Response + Complete Response + Stable Disease) of 19% at 24 weeks and enzalutamide showed a CBR of 35% at 16 weeks. VT-464 is an oral non-steroidal, small molecule that is a potent anti-androgen through both inhibition of CYP17 lyase and through direct inhibition of AR. Studies in breast cancer cell lines have shown that VT-464 inhibits growth in a soft agar assay of MCF7 (ER positive/low AR expression), tamoxifen-resistant MCF7, and MDA-MB-453 (ER negative/AR positive) cells in a dose dependent manner and with higher potency than enzalutamide. Patients with AR+ TNBC may benefit from treatment with VT-464. In addition, since VT-464 will deplete androgen available for aromatization, men with ER-positive (ER+) breast cancer may benefit from use of VT-464. Methods: This is a Phase 2, open label study evaluating the potential benefit of VT-464 in female patients with TNBC with AR 1 to 9% (cohort 1) and AR ≥ 10% (cohort 2), and men with ER+ breast cancer (cohort 3) (NCT02130700; NIH 14-c-0090). VT-464 will be administered once daily in continuous 28-days cycles. Due to differences in drug metabolism, women with TNBC will receive VT-464 450mg by mouth daily while men with ER+ breast cancer will receive VT-464 600mg by mouth daily. In the two female TNBC cohorts the primary endpoint is CBR at 16 weeks. In the ER+ male breast cancer cohort the primary endpoint is progression free survival at 24 weeks. Secondary objectives include evaluation of response rate and the safety profile of the drug in both populations. Women with TNBC with > 1% AR expression per IHC are eligible. Males with ER+ breast cancer, who have failed at least one prior endocrine therapy and are undergoing gonadal suppression using LHRH agonists or antagonists are eligible for the study. All patients must be at least 18 years old and have a ECOG of 0 to 1. Consenting patients must have biopsiable disease which will be used for genomic and transcriptomic evaluation before and after treatment with VT-464. Correlative studies including serum hormone levels, circulating tumor cells, and immune subset will be analyzed. Patients must also have adequate hematopoietic, hepatic and renal function. Exclusions include symptomatic CNS metastases, radiotherapy within 28 days of study entry a