224 Background: High-risk prostate cancer has a significant risk of recurrence when treated with unimodal therapy. The utility of neoadjuvant therapy prior to radical prostatectomy (RP) has yet to be defined. The ACDC-RP study investigated the use of abiraterone acetate (AA) + prednisone (P) + leuprolide (LHRH) with or without cabazitaxel prior to RP in high-risk patients. Methods: This phase II trial randomized patients to Arm A (AA/P + LHRH + cabazitaxel 20 mg/m2 with peg-filgrastim 6 cycles) or Arm B (AA/P + LHRH) for 6 months prior to RP. The primary objective was to compare the rate of pathological complete response (CR) or minimal residual disease (MRD) between treatment arms. MRD was defined as ≤5% of prostate volume involved by tumor. We present RP pathological outcomes, safety signals, and early biochemical response data. Results: Out of 78 randomized participants, 70 completed the full course of study treatment and underwent RP. Across both treatment arms, 31 (44%) men achieved either CR or MRD; 5 men had CR (2 in Arm A) and an additional 26 men exhibited MRD (15 in Arm A), p = 1 between Arm A and B. Kaplan-Meier analysis demonstrated no difference in biochemical-free survival (BFS) rate between the two treatment groups. Patients who achieved a CR/MRD experienced significantly longer BFS. Conclusions: Study findings indicate significant tumor response with 44% of patients exhibiting CR/MRD, with no significant difference observed between the two treatment arms. Patients who exhibit CR/MRD experienced better BFS rates. Genomic efforts are underway to determine predictors of response. Clinical trial information: NCT02543255. [Table: see text]