Sequencing of Sipuleucel-T and ADT in Men With Non-metastatic Prostate Cancer

Multicenter, randomized, open-label study, with subjects allocated (1:1) to 1 of 2 study arms, using a stratified randomization based on:

• Prostate-specific antigen doubling time (PSADT): ≤ 3 months or > 3 months and ≤ 12 months. • Primary therapy: radical prostatectomy (RP) or radiation, including brachytherapy, (XRT) or RP + XRT.

Arm 1: Subjects received one infusion of sipuleucel-T every two weeks for a total of three infusions. Two weeks after the third sipuleucel-T infusion, subjects started ADT with 45 mg leuprolide acetate depot injection (Eligard® 45 mg). An additional leuprolide acetate injection was administered at 6 months after the first injection for a total of 2 injections and 12 months of ADT.

Arm 2: Subjects started ADT with 45 mg leuprolide acetate depot injection (Eligard® 45 mg) 12 weeks before infusion 1 of sipuleucel-T. An additional leuprolide acetate injection was administered at 6 months after the first injection for a total of 2 injections and 12 months of ADT. Twelve weeks after the initial leuprolide 45 mg depot injection, subjects began one infusion of sipuleucel-T every two weeks for a total of three infusions.

Cellular and humoral immune responses were assessed for Arm 2 subjects at 12, 8, and 4 weeks pre infusion 1, and in all subjects (both arms) at pre-leukapheresis 1, 2, and 3, and post-infusion 1, 2 and 3, and at the following time points after the third infusion: Weeks 2, 6, and 12 and Months 6, 9, 12, 15, 18, 21, and 24.

Safety assessments included adverse event (AE) monitoring, laboratory tests (complete blood count (CBC) and serum chemistry), vital signs, Eastern Cooperative Oncology Group (ECOG) performance status, physical examination, as well PSA and testosterone monitoring. The study was complete at the 27-Month visit for Arm 1 and the 24-Month visit for Arm 2.

Inclusion criteria

• Hormone-sensitive prostate cancer
• Non-metastatic disease, as evidenced by negative bone scan or computed tomography of the abdomen and pelvis
• ECOG performance status ≤ 1
• Histologically documented prostate cancer
• Prior primary therapy for prostate cancer
• Rising PSA with a PSADT of ≤ 12 months
• Testosterone ≥ 200 ng/dL ≤ 28 days of registration
• Adequate hematologic, renal, and liver function
• Must live in a permanent residence within a comfortable driving distance (round-trip within one day) to the clinical research site

Exclusion criteria

• Requires systemic ongoing immunosuppressive therapy
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to sipuleucel-T or GM-CSF
• Prior sipuleucel-T therapy
• Prior ADT therapy ≤ 6 months prior to registration or ≥ 6 months duration in total
• If subject has a history of any other stage III/IV malignancy, the subject must be disease free and off any malignancy-related treatment for at least 10 years. If the subject has a history of any stage I-II malignancy, the subject must be disease free and off any malignancy-related treatment for at least 5 years.
• Prior experimental immunotherapy or on an experimental clinical trial within 1 year
• Received denosumab or XRT ≤ 6 months prior to registration
• Received chemotherapy or GM-CSF ≤ 90 days prior to registration
• Received any of the following medications or interventions ≤ 28 days prior to registration

• major surgery requiring general anesthesia
• systemic immunosuppressive therapy
• other prescription treatment for prostate cancer
• Active infection within 1 week of registration
• Likely to receive XRT or surgery for prostate cancer during the study period
• Any medical intervention, any other condition, or any circumstances that could compromise the study.