Background:Abiraterone acetate (A) and cabazitaxel (C) improve survival for patients with mCRPC. We conducted an open-label trial of A+C to assess the antitumor activity and tolerability of the combination in patients (pts) previously treated with docetaxel (D) and A (NCT01511536). Here, we report results for the phase 2 part of the study, after the combination MTD was established (Massard C, et al. ASCO 2013). Methods: Pts received A (1,000 mg QD) and C (25 mg/m² every 3 weeks) with prednisone/ prednisolone (5 mg BID). Eligibility criteria included prior D and prior A for at least 3 months, disease progression by rising PSA, ECOG PS 0–1 and no prior C or mitoxantrone. The primary endpoint was PSA response rate (PSA-RR: ≥50% decrease confirmed ≥3 weeks later). A 1-sided exact test was planned to test a null hypothesis of PSA-RR 25%, with a type 1 error of 0.05. With a sample size of 26, this test would have a power of 83% under the alternative hypothesis of PSA-RR 50%. Secondary endpoints included progression-free survival (PFS), duration of response, radiological-RR, overall survival and safety. Results: Twenty-seven pts were treated in this phase 2 part of the study. The median time on A prior to A+C was 8.3 months (range 3.1–29.8). All pts previously received D and A; 4 pts (15%) had also received prior treatment with enzalutamide. The median number of C cycles administered was 7 (range 1–21). Main treatment-emergent adverse events (AE) Grade≥3 were neutropenia (15 pts; 55%; 1 pt [3.7%] had febrile neutropenia), fatigue (4 pts; 15%) and sepsis (3 pts; 11%). Seven pts (25.9%) required a dose reduction of C due to AE, but all patients received ≥80% of the planned dose intensity. Of 26 pts evaluable for the primary endpoint, 12 achieved a PSA response (PSA-RR 46.2%; 95% CI 26.6–66.4%), and therefore the null hypothesis was rejected (p<0.01). Median PSA-PFS was 6.9 mo (95% CI 4.1–10.2 mo). Three out of 14 pts (21%) with measurable disease achieved a partial response per RECIST 1.1. Conclusions: The combination of abiraterone and cabazitaxel is well tolerated and demonstrated antitumor activity in the post-docetaxel, post-abiraterone setting. Clinical trial information: NCT01511536