Background: Galeterone is a 1st in class oral small molecule that disrupts androgen receptor (AR) signaling via multi-targeted mechanism of action (1) selective inhibition of CYP17 lyase; (2) competitive antagonism of androgen binding to AR; and (3) degrading of AR protein. CYP17 enzyme inhibition (abiraterone) and AR antagonism (enzalutamide) separately have shown significant activity in metastatic castrate resistant prostate cancer (mCRPC) and considered standard treatment for these pts. Galeterone is a single molecule that has the potential advantage to target both mechanisms. Methods: ARMOR2 (NCT# 01709734) is a 2 Pt Phase 2 study designed to confirm dose of reformulated galeterone (spray dry dispersion; SDD) (Pt 1) and assess the safety and efficacy of the dose, 2550 mg QD for 12 wks, in 4 distinct CRPC pt cohorts; non-metastatic tx naïve (M0 TN, n= 7, median PSA=15.6 ng/dL, median PSA DT=2.30 mo), metastatic tx naïve (M1 TN, n=24, median PSA = 22.9 ng/dL, median PSA DT=2.3 mo), abiraterone refractory (Abi-R, n=11, median PSA=35.8 ng/dL, median PSA DT=1.57 mo) and enzalutamide refractory (Enza-R, n=2, median PSA = 72.85 ng/dL, median PSA DT=1.97 mo). This abstract presents interim results of the 2550 mg dose for pts treated in both Pt 1 and 2. Results: Response was seen at 2550 mg in all tx groups, including decreases in PSA. In the most mature dataset of 24 M1 TN pts, PSA decreases of 30% (92%), and 50% (83%) were reached. Data on the M1 group showed encouraging preliminary objective responses (ORR) in 7 of 8 (86%) evaluable pts at 3 months. Safety: Drug was well tolerated by all tx groups. 94% of all adverse events (AE) were gr1 or 2 in severity. Most common < gr 2 AEs were GI (nausea, diarrhea), fatigue and pruritis with no mineralocorticoid excess (ME) or seizures. Conclusions: SDD Galeterone has shown significant biochemical activity and preliminary clinical activity and is well tolerated with no ME or seizures. These data support continued testing of this unique compound in pts with prostate cancer. Clinical trial information: NCT01709734.

*N= # of pts completing 12 wks, reached PSA 50 or terminated early. **N= # of pts completing 12 wks.