Background: Coadministration of D and AA may be beneficial due to complementary mechanisms of action. A phase 1b safety and pharmacokinetic (PK) study assessed the safety and efficacy of D + AA. Methods: 3 cohorts (C) of chemo-naive mCRPC pts received escalating doses of D + AA. Primary end point: proportion of pts with dose-limiting toxicity (DLT) between Wks 2 and 7, defined as grade (Gr) ≥ 3 non-heme toxicity, Gr 4 neutropenia > 7 days (or febrile neutropenia), Gr 4 thrombocytopenia, or other intolerable toxicity. Pts could continue AA after discontinuing D. D + AA was deemed safe if ≤ 2 pts/C experienced DLT; the maximum tolerated dose (MTD) was the highest safe combination of D + AA. PSA changes and PK parameters were evaluated. Results: 22 pts were treated; 18 pts were evaluable for DLT assessment. The combination dose received by C3 (1 pt had DLT) was deemed the MTD. With treatment ongoing, 90% and 70% of pts had ≥ 50% and ≥ 90% PSA decline from baseline, respectively (Table). With median follow-up of 11.8 months, there were 5 PSA progression events. PK parameters were comparable for both abiraterone and D alone and in combination. Conclusions: D + AA was well tolerated at full doses of each drug. PK was comparable when D and AA were given alone and in combination. The efficacy signal may justify further study. Clinical trial information: NCT01400555.

^aAA and prednisone taken daily. D administered once q3wk; ^bC3 data is limited; ^cPt had elective cystolitholapaxy for preexisting hematuria.