5024 Background: Six-transmembrane epithelial antigen of the prostate-1 (STEAP1) protein is a cell-surface protein frequently overexpressed in prostate cancer. The ADC DSTP3086S contains the humanized IgG1 anti-STEAP1 monoclonal antibody linked to the potent anti-mitotic agent MMAE. Methods: This study evaluated safety and activity of DSTP3086S (0.3-2.8 mg/kg IV) given every 3 weeks (q3w) to pts with CRPC. A traditional 3+3 design was used to determine maximum-tolerated dose, followed by cohort expansion at the recommended Phase II dose (RP2D). Clinical activity was evaluated per PCWG2 criteria. Results: As of 18 Dec 2013, 59 pts were enrolled with a median age of 68 (43-87), all ECOG PS 0-1, and with a median of 6 prior systemic regimens (71% received prior taxanes). Pts received a median of 3 doses (range 1-14) of DSTP3086S, with 14 pts (24%) still ongoing. Two patients in dose escalation (1 at 2.25 mg/kg and 1 at 2.8 mg/kg) had dose limiting G3 transaminitis. Cohort expansion started at 2.8 mg/kg (n=10...