Phase (Ph) 2 stage 1 clinical activity of seviteronel, a selective CYP17-lyase and androgen receptor (AR) inhibitor, in women with advanced AR+ triple-negative breast cancer (TNBC) or estrogen receptor (ER)+ BC: CLARITY-01

1102 Background: Seviteronel (Sevi), an oral selective CYP17-lyase and AR inhibitor that blocks testosterone and estradiol production and competitively antagonizes the AR, is in Ph 2 clinical development for BC and prostate cancer. The primary objective of this ongoing Ph 2 study (NCT02580448) is to estimate the activity of once daily Sevi in women with AR+ TNBC and ER+ BC as measured by clinical benefit rate (CBR) at 16 and 24 weeks (wk), respectively. Methods: Patients (pts) with ER+/HER2-normal metastatic BC following progression of ≥1 prior line of endocrine therapy or TNBC were enrolled with no limit of prior therapies in either cohort. Evaluable pts had AR ≥10% via central IHC staining (TNBC only) and 1 post-baseline scan. Sevi was administered at 450 mg oral daily. Scans were performed every 8 wk. Circulating tumor cell (CTC) enumeration was performed by EPIC CTC analysis. A Simon’s 2-stage design was employed to determine activity (≥2 of 13 CBR16 in TNBC and ≥2 of 12 CBR24 in ER+ BC allow for accrual to Stage 2). Results: As of 4 Oct, 2016, 16 pts with AR+ TNBC (6 evaluable) and 14 pts with ER+ BC (11 evaluable) were enrolled. 67% had visceral metastases; 10% had stable brain metastases. 60% had ≥2 lines of prior therapy for advanced disease. 13 of 14 (93%) TNBC pts who underwent central AR testing had AR ≥10%. Four pts in the TNBC cohort and 8 pts in the ER+ cohort remain on therapy. CBR16 (TNBC) and CBR24 (ER+) was 2 of 6 (33%) and 2 of 11 (18%) allowing Stage 2 accrual in both cohorts. 7 of 10 evaluable pts with CTCs present at baseline had a CTC decline at C2D1, including all that met CBR (-94.3% [-27.5, -100] median [range]). The most common adverse events (≥ 25%) were fatigue (50%), nausea (43%) and decreased appetite (33%); all Grade 1/2. Updated CBR data will be presented at the time of presentation. Conclusions: Sevi Stage 1 activity is suggested by CBRs, along with associated CTC declines in heavily pre-treated pts with high disease burden. The observed safety profile is consistent with on-target pharmacology. Stage 2 enrollment is ongoing. Sevi may provide a novel treatment option for women with AR+ TNBC or ER+ BC. Clinical trial information: NCT02580448.