Safety, efficacy, and pharmacodynamics of the investigational agent TAK-700 in metastatic castration-resistant prostate cancer (mCRPC): Updated data from a phase I/II study.

98 Background: The investigational agent orteronel (TAK-700) is a selective 17,20 lyase inhibitor that down regulates androgenic steroid production in vitro and in vivo. Since phase 1 data in patients (pts) with mCRPC were promising, this open-label, multicenter study was expanded to gather additional data on safety and antitumor activity. Methods: The phase 2 portion of this study included four additional dose cohorts. Pts had no prior chemotherapy, and had baseline testosterone <50 ng/dL and prostate-specific antigen (PSA) ≥5 ng/mL. Results: 97 pts received orteronel 300 mg BID (n=23), 400 mg BID + prednisone 5 mg BID (n=24), 600 mg BID + prednisone (n=26), or 600 mg QD (n=24). At data cut-off (23 May 2011), 62% of pts had withdrawn (including 19% due to AEs and 19% for disease progression [PD]). Most common AEs were fatigue (76%), nausea (47%), and constipation (38%); most common grade ≥3 AEs were fatigue (12%) and hypokalaemia (8%). PSA response rates (≥50% decrease) at 12 wks were 63%, 50%, 41%, and ...