Background: ADT is a standard therapy for pts with BRPC after failure of primary therapy, and has known immunomodulatory effects. Sipuleucel-T is an autologous cellular immunotherapy that targets prostatic acid phosphatase (PAP) and is FDA approved for minimally or asymptomatic metastatic castrate-resistant prostate cancer. Here we report interim data from a phase 2 trial evaluating the optimal sequencing of sipuleucel-T and ADT by examining immune response markers in pts with BRPC at high risk for metastases (i.e., PSA doubling time ≤12 mo). Methods: Men were equally randomized to Arm 1: sipuleucel-T followed by ADT (started 2 wk after the final sipuleucel-T infusion); or Arm 2: ADT followed by sipuleucel-T (started after 3 mo of ADT). In both arms pts received 3 infusions of sipuleucel-T and 12 mo of ADT (2 × 45 mg leuprolide injections at 6 mo intervals). The primary endpoint was antigen-specific immune responses (ELISPOT to PA2024 [PAP-GM-CSF]). Secondary endpoints included safety and product parameters (CD54 upregulation, CD54⁺ and total nucleated cell counts). Results: 68 pts were randomized over 9 mo. Baseline characteristics were balanced across arms. Product parameters, evaluated in 31 and 17 pts in Arms 1 and 2, respectively, were similar between arms at the time of this analysis (26 Sept 2012). Antigen presenting cell activation patterns indicated a prime-boost effect (increased CD54 upregulation at infusions 2 and 3). Analysis of serum samples suggested that there were no differences between the arms in cellular (n=20; n=10) or humoral (n=22; n=13) immune responses to PA2024 or PAP (p>0.05). Similar anti-tetanus titers were seen in both arms, indicating equivalent immunocompetence. To date, the combination of sipuleucel-T and ADT appears to be well tolerated with only 1 serious adverse event seen (vertigo, Arm 2). Conclusions: Preliminary data suggest that in men with BRPC, sipuleucel-T results in a similar prime-boost pattern of immune activation, and antigen-specific cellular and humoral responses, independent of ADT. Sipuleucel-T plus ADT appears to be well tolerated in these pts. Updated results will be presented. Clinical trial information: NCT01431391.