Concurrent vs. Sequential Sipuleucel-T & Abiraterone Treatment in Men With Metastatic Castrate Resistant Prostate Cancer

Subjects underwent screening procedures at the Screening Visit to ensure that they met the
inclusion and exclusion criteria outlined in the protocol. Subjects were evaluated for
eligibility criteria, and if eligible, were registered and randomized in a 1:1 into either
the Concurrent Arm or the Sequential Arm.

Subjects in both arms underwent a standard 1.5 to 2.0 blood volume leukapheresis, followed
approximately 3 days later by an intravenous (IV) infusion of sipuleucel-T. This process
occurred at approximately 2-week intervals. A course of sipuleucel-T treatment comprised
three infusions.

Following the first infusion, subjects were limited to a maximum of three total product
failures for all subsequent infusions, due specifically to insufficient total nucleated cell
(TNC) count and/or CD54 upregulation. These subjects received no further leukaphereses or
sipuleucel-T infusions, but did receive abiraterone acetate plus prednisone per the schedule
of the arm to which they were randomized. All subjects received a total of 26 weeks of
abiraterone acetate plus prednisone therapy.

All immune monitoring (IM) endpoints were collected from all subjects who received at least
one infusion. Cellular and serological immune responses were assessed for subjects in both
arms. In both arms, IM blood samples were collected at baseline (screening);
pre-leukapheresis 2 and 3; post-infusion 1, 2, and 3; and weeks 6, 10, 14, and 26, with the
timing of IM visits based on the onset of treatment (Day 0). Day 0 was the day of the first
infusion. Post-infusion blood draws occurred at 3 hours (allowable window 1-24 hours) after
each infusion. If a subject received only one or two infusions, immune samples were still
drawn at the scheduled time points based on the first infusion (Day 0). If the subject was
not scheduled to undergo further leukapheresis, no other pre-leukapheresis procedures were
conducted.

During the active follow-up phase, subjects were followed from registration through the
Post-Treatment Visit (30-37 days post-last study treatment), or until disease progression,
unacceptable toxicity, or death, whichever occurred first.

During the long-term follow-up (LTFU) phase, subjects were followed from the Post-Treatment
Visit for up to 3 years from the date of registration/randomization. During the LTFU phase,
only new treatment-related serious adverse event (SAE)s, cerebrovascular event (CVE)s
(regardless of causality), the first anti-cancer therapy and first chemotherapy, and survival
status were collected via a quarterly telephone call.

Overall survival was measured as the time from randomization until death over a 3-year
period.

Inclusion Criteria:

- histologically documented prostate cancer confirmed by a pathology report from
prostate biopsy or radical prostatectomy specimen

- metastatic status as evidenced by imaging obtained demonstrating bone metastasis or lymph node metastasis

- castrate resistant prostate cancer: castrate levels of testosterone ( evidence of disease progression concomitant with surgical or medical castration

- serum PSA >/= 2.0 ng/mL

- castrate levels of testosterone ( castration

- baseline Eastern Cooperative Oncology Group (ECOG) performance status of
- systolic blood pressure (BP)
- adequate baseline hematologic, renal, and liver functions

- must live in a permanent residence within a comfortable driving distance (round trip
within one day) of the clinical trial site

Exclusion Criteria:

- the presence of known lung, liver, or brain metastases, malignant pleural effusions,
or malignant ascites

- New York Heart Association Class III or IV heart failure

- any medical condition that may be compromised by increases in blood pressure,
hypokalemia, or fluid retention

- Child-Pugh Class B or C hepatic insufficiency

- spinal cord compression, imminent long bone fracture, or any other condition likely to
require radiation therapy and/or steroids for pain control

- known adrenalcortical insufficiency

- any medical contraindications to receiving prednisone

- prior treatment with sipuleucel-T

- previous treatment with abiraterone acetate (Zytiga(R)) or ipilimumab (Yervoy(TM))

- a requirement for systemic immunosuppressive therapy for any reason. Use of inhaled,
intra-nasal, intra-articular, and topical steroids was allowed.

- treatment with any investigational vaccine or immunotherapy

- treatment with any chemotherapy prior to registration.

- a history of stage III or greater cancer, excluding prostate cancer. Basal or squamous
cell skin cancers must have been adequately treated and the subject must be
disease-free at the time of registration. Subjects with a history of stage I or II
cancer must have been adequately treated and been disease-free for ≥ 3 years at the
time of registration.

- myocardial infarction or ventricular or atrial arrhythmia within 6 months prior to
registration

- ongoing anti-androgen withdrawal response.

- systemic steroid use within ≤ 60 days of registration

- treatment with denosumab (Xgeva(R) or Prolia (R)) within ≤ 3 months prior to
registration

- positive test for human immunodeficiency virus (HIV) or human T cell lymphotrophic
virus (HTLV) infections. Subjects with a positive test for hepatitis B or hepatitis C
were allowed provided they meet the liver function test (LFT) criteria and have no
signs of acute infection or active disease.

- treatment with any of the following medications or interventions within 28 days prior
to registration: external beam radiation or major surgery requiring general
anesthetic; saw palmetto; megestrol acetate (Megace(R)), diethylstilbestrol, and
cyproterone; 5-alpha-reductase inhibitors (e.g. finasteride [Proscar(R)], dutasteride
[Avodart(R)]); steroidal anti-androgen therapy; any other systemic therapy for
prostate cancer, except for medical castration; treatment with any other
investigational product for prostate cancer; substrates of CYP2D6 (e.g. including but
not limited to thioridazine); inhibitors of CYP3A4 (e.g. including but not limited to
ketoconazole, itraconazole, clarithromycin, nefazodone, telithromycin, and
voriconazole); inducers of CYP3A4 (e.g. including but not limited to phenytoin,
carbamazepine, rifampin, rifapentine, and phenobarbital)

- a requirement for treatment with opioid analgesics within 21 days prior to
registration

- an active infection or infection requiring parenteral antibiotic therapy or causing
fever within 7 days of registration

- any medical intervention, or other condition, or any other circumstance that, in the
opinion of the Investigator or the Dendreon Medical Monitor, could compromise
adherence with study requirements or otherwise compromise the study's objectives