A Randomized Phase 3, Open-Label Trial of Sipuleucel-T Administered To Patients On Active Surveillance For Newly Diagnosed Prostate Cancer
Phase: PHASE3
Conditions: Adenocarcinoma of the Prostate
Sponsor: Dendreon

P17-1 (ProVent) Protocol 
PR-2677.02, 25 January 2019  
Page 1 of 78 
Dendreon Pharmaceuticals LLC 
 
 
Proprietary and Confidential 
A RANDOMIZED PHASE 3, OPEN-LABEL TRIAL OF SIPULEUCEL-T 
ADMINISTERED TO PATIENTS ON ACTIVE SURVEILLANCE FOR NEWLY 
DIAGNOSED PROSTATE CANCER 
 
IND NUMBER: 
BB-IND-006933 
INVESTIGATIONAL PHASE: 
3 
PROTOCOL NUMBER: 
P17-1 
INVESTIGATIONAL PRODUCT: 
Sipuleucel-T 
ORIGINAL PROTOCOL ISSUE 
DATE: 
13 June 2018 
Amendment 1 Issue Date: 
Amendment 2 Issue Date: 
 
06 November 2018 
25 January 2019 
 
STUDY SPONSOR: 
Dendreon Pharmaceuticals LLC 
1208 Eastlake Avenue East  
Seattle, WA 98102 
 
Contract Research Organization: 
Pharmaceutical Research Associates 
 
4130 Park Lake Avenue, Suite 400 
 
Raleigh, NC  27612 
 
Medical Monitor 
Biostatistician 
Clinical Trial Manager 
Bruce Brown, MD 
Matthew Harmon 
Shabnam Vaziri 
(206) 219-1090 (Tel) 
(206) 829-1531 (Tel) 
(206) 455-2323 (Tel) 
Bruce.Brown@dendreon.com mharmon@Dendreon.com 
svaziri@Dendreon.com 
 
 
CONFIDENTIALITY STATEMENT 
This document is the property of Dendreon Pharmaceuticals LLC (“Dendreon”).  It contains 
confidential and proprietary information belonging to Dendreon; therefore, its use is intended 
solely for physicians, contractors, clinical trial site personnel, and contract research 
organizations participating in the Dendreon-sponsored clinical study to which this document 
pertains (“study personnel”).  Reproduction and distribution is authorized for and strictly 
limited to such study personnel.  Reproduction for any other purpose, and any other 
distribution of this document, is prohibited. 

P17-1 (ProVent) Protocol 
PR-2677.02, 25 January 2019  
Page 2 of 78 
Dendreon Pharmaceuticals LLC 
 
 
Proprietary and Confidential 
PRINCIPAL INVESTIGATOR PROTOCOL SIGNATURE PAGE 
 
A Randomized Phase 3, Open-label Trial of Sipuleucel-T Administered to Patients on Active 
Surveillance for Newly Diagnosed Prostate Cancer 
 
Amendment 2:  25 January 2019 
 
By signing below, the Principal Investigator agrees to adhere to the protocol. 
Principal Investigator Name:
 
____________________________________________________ 
Title:  
 
 
____________________________________________________ 
Address: 
 
 
____________________________________________________ 
Address: 
 
 
____________________________________________________ 
Address: 
 
 
____________________________________________________ 
Email:  
 
 
____________________________________________________ 
Phone:  
 
 
____________________________________________________ 
Facsimile: 
 
 
____________________________________________________ 
Signature: 
 
 
____________________________________________________ 
Date:  
 
 
____________________________________________________ 

P17-1 (ProVent) Protocol 
PR-2677.02, 25 January 2019  
Page 3 of 78 
Dendreon Pharmaceuticals LLC 
 
 
Proprietary and Confidential 
PROTOCOL SYNOPSIS 
Protocol Title: A Randomized Phase 3, Open-Label Trial of Sipuleucel-T Administered to 
Patients on Active Surveillance for Newly Diagnosed Prostate Cancer 
Protocol Number: P17-1 
Clinical Phase: 3 
Investigational Product, Dosage Form, Route, and Dose Regimen: 
Sipuleucel-T is an autologous cellular immunotherapy available as a suspension for 
intravenous infusion.  Sipuleucel-T consists of autologous peripheral blood mononuclear cells 
(PBMC), including antigen presenting cells (APCs) that have been activated during a defined 
culture period with a recombinant human protein, PAP-GM-CSF, consisting of prostatic acid 
phosphatase (PAP), an antigen expressed in prostate cancer tissue, linked to granulocyte-
macrophage colony-stimulating factor (GM-CSF), an immune cell activator.  Each dose of 
sipuleucel-T contains a minimum of 50 million autologous CD54+ cells activated with PAP-
GM-CSF, suspended in 250 mL of Lactated Ringer's Injection, USP. 
The active components of sipuleucel-T are autologous APCs and PAP-GM-CSF.  During 
culture, the recombinant antigen binds to and is processed by APCs into smaller protein 
fragments.  The recombinant antigen is designed to target APCs, and may help direct the 
immune response to PAP.  Minimal residual levels of the intact PAP-GM-CSF are detectable 
in the final sipuleucel-T product. 
The patient's PBMCs are obtained via a standard leukapheresis procedure approximately 3 days 
prior to the infusion date.  Due to the autologous nature of sipuleucel-T, it is important that the 
patient and physician adhere to the personalized leukapheresis and infusion schedules. 
The cellular composition of sipuleucel-T is dependent on the composition of cells obtained 
from the patient's leukapheresis.  In addition to APCs, the final product contains T cells, B 
cells, natural killer (NK) cells, and other cells.  The number of cells present and the cellular 
composition of each sipuleucel-T dose will vary. 
The potency of sipuleucel-T is in part determined by measuring the increased expression of the 
CD54 molecule, also known as ICAM-1, on the surface of APCs after culture with PAP-GM-
CSF. CD54 is a cell surface molecule that plays a role in the immunologic interactions between 
APCs and T cells, and is considered a marker of immune cell activation. 
In-process and final sterility tests are initiated prior to shipping, but the final results are not 
available for up to 7 days.  Sipuleucel-T is released for shipping based on acceptable results 
from 2-day incubation of the in-process sterility test (Sipuleucel-T, 2017). 

P17-1 (ProVent) Protocol 
PR-2677.02, 25 January 2019  
Page 4 of 78 
Dendreon Pharmaceuticals LLC 
 
 
Proprietary and Confidential 
Reference Product, Dosage Form, Route, and Dose Regimen:  
No reference product will be used in this clinical study. 
Primary Objective: 
• To assess the efficacy of sipuleucel-T in reducing histopathologic reclassification to a 
higher Gleason grade in prostate cancer subjects on active surveillance (AS) 
Secondary Objectives: 
• To assess the differential receipt of local or systemic therapy (surgery, radiation, 
androgen deprivation therapy (ADT)) in each study arm, and the reasons for receipt of 
further local or systemic therapy  
• To assess differences in quality of life (i.e., patient-reported outcomes (PRO)) between 
sipuleucel-T and control arms 
• To evaluate the safety of sipuleucel-T in men with low to intermediate risk localized 
prostate cancer 
Exploratory Objectives: 
• To evaluate in the sipuleucel-T arm the association of peripheral blood and tumor 
microenvironment immunologic responses with reclassification of Gleason grade over 
time  
• To evaluate clinical assessments and potential correlation to sipuleucel-T 
• To evaluate prostate tissue genomics 
Primary Endpoint: 
• Proportion of subjects without histological reclassification (Gleason group upgrade) 
within 36 months of randomization as determined by Blinded Independent Central 
Review (BICR) 
o Upgrade is defined as subjects at randomization with either International Society of 
Urological Pathology (ISUP) Grade Group 1 (Gleason 3+3) upgraded to Grade 
Group 2 (Gleason 3+4) or higher or subjects at randomization with Grade Group 2 
upgraded to Grade Group 3 (Gleason 4+3) or higher. 
Secondary Endpoints: 
• To determine the number of subjects with subsequent prostate cancer treatment (e.g., 
surgery, radiation, ADT) in each study arm 

P17-1 (ProVent) Protocol 
PR-2677.02, 25 January 2019  
Page 5 of 78 
Dendreon Pharmaceuticals LLC 
 
 
Proprietary and Confidential 
• Characterization of PROs by Memorial Anxiety Scale for Prostate Cancer (MAX-PC), 
Short Form 12 Health Survey (SF-12), The Expanded Prostate Cancer Index Composite 
for Clinical Practice (EPIC-CP), International Prostate Symptom Score (IPSS) at 
baseline and 12-, 24-, and 36-month visits after randomization 
• To evaluate safety by determining the incidence of adverse events (AEs), assessing 
laboratory data for clinically significant laboratory abnormalities and evaluating 
physical examination (PE) findings in each study arm  
Exploratory Endpoints: 
• To calculate the correlation of prostate tissue and peripheral immune responses, as well 
as product parameters to sipuleucel-T efficacy 
• To determine, in the cohort of subjects having a radical prostatectomy, the number of 
subjects with an ISUP Grade Group change (up- or down-grade) determined by BICR 
from radical prostatectomy tissue histology in each study arm 
• To measure the percentage of subjects with a negative biopsy at any post-randomization 
biopsy assessment in each study arm  
• To compare the proportion of subjects with clinical risk group progression (e.g., Cancer 
of the Prostate Risk Assessment (CAPRA) and National Comprehensive Cancer 
Network (NCCN) prostate cancer risk groups) between study arms 
• To calculate Prostate-specific antigen (PSA) velocity from randomization through 
study completion in each study arm  
• To determine the association of prostate cancer tissue genomic profile and sipuleucel-T 
treatment 
Study Design and Duration: 
This is a multicenter, randomized, open-label study of immunotherapy with sipuleucel-T 
compared to control subjects followed on AS.  The study will enroll subjects being followed 
by AS and initially diagnosed within 12 months prior to Screening with either ISUP Grade 
Group 1 or 2 adenocarcinoma of the prostate. 
This study consists of 3 phases (see Table 1 and Table 2): 
Screening Phase:  
The Screening Phase will begin at the completion of the informed consent process and 
continues until randomization.  Screening procedures will be performed up to 30 days prior to 
randomization. 
 

P17-1 (ProVent) Protocol 
PR-2677.02, 25 January 2019  
Page 6 of 78 
Dendreon Pharmaceuticals LLC 
 
 
Proprietary and Confidential 
The following assessments will be performed on all subjects during the Screening Phase:  
• BICR of prostate biopsy slides obtained from local pathologist (ISUP Grade Group and 
Gleason Score) 
• Clinical evaluations (demographics, medical history, PE & vital signs, digital rectal 
examination (DRE), Eastern Cooperative Oncology Group (ECOG) performance 
status, cardiovascular risk assessment & electrocardiogram (ECG)) 
• Cardiovascular and thrombosis disease history  
• Concomitant medications 
• All anti-prostate cancer therapies  
• PROs/Quality of life questionnaires  
• Virology serology (HBsAg, HBsAb, HBcAb, HCV antibody (Ab), if Ab positive (Ab+) 
then HCV RNA), HIV-1, HIV-2 antibody screen and HTLV-1, HTLV-2 antibodies 
• Hematology and chemistry 
• PSA 
• Total testosterone 
Active Phase:  
The Active Phase will begin at randomization and continues through completion of the end of 
Active Phase study visit (within 30 days of Biopsy 2) or until the study is terminated by the 
sponsor.   
Subjects who withdraw consent and discontinue from the study prior to completing the end of 
Active Phase study visit will undergo an Early Withdrawal visit within 30 days following 
discontinuation notice. Subjects are encouraged to have, a s standard of care, a systematic 
prostate biopsy (≥10 cores) with or without MRI at the investigator’s discretion prior to study 
withdrawal.  The H&E and special-stained slides from this biopsy will be submitted for BICR 
determination of their ISUP Grade Group classification prior to study withdrawal. 
After Screening assessments are completed, eligible subjects will be randomized 2:1 to the 
sipuleucel-T arm or the control arm.  Subjects randomized to sipuleucel-T arm will undergo 
their first leukapheresis within 60 days of randomization and will receive 3 infusions of 
sipuleucel-T at approximately 2-week intervals.  Subjects randomized to the control arm will 
be followed on AS as described in the schedule of events (Table 2).  
Subjects randomized to the sipuleucel-T arm will be evaluated at 0, 2, 4, 6, 10, 14, and 26 
weeks following the first infusion for: 

P17-1 (ProVent) Protocol 
PR-2677.02, 25 January 2019  
Page 7 of 78 
Dendreon Pharmaceuticals LLC 
 
 
Proprietary and Confidential 
• Immune responses (Week 0 prior to first infusion is baseline) 
• All anti-prostate cancer therapies 
• Concomitant medications 
• AEs and serious adverse events (SAEs) (per reporting requirements for the sipuleucel-
T arm)  
Subjects randomized to the control arm will be evaluated (office visit or phone) at 3 months 
following randomization for:  
• Survival status  
• All anti-prostate cancer therapies 
• Concomitant medications 
• All AEs and SAEs 
Subsequently, all subjects in the sipuleucel-T and control arms will be followed every 6 months 
from date of randomization for at least 36 months for: 
• Immune responses (sipuleucel-T arm only) 
• Survival status  
• PSA levels (should be collected prior to DRE and biopsy procedures) 
• DRE assessments 
• Prostate cancer disease progression 
• All anti-prostate cancer therapies 
• Concomitant medications 
• All AEs and SAEs  
Note, for subjects randomized to the sipuleucel-T arm, scheduled events for the 26-week visit 
post first infusion and first 6-month visit post-randomization may take place on the same visit 
and only one set of immune samples need to be collected  
 
 
 

P17-1 (ProVent) Protocol 
PR-2677.02, 25 January 2019  
Page 8 of 78 
Dendreon Pharmaceuticals LLC 
 
 
Proprietary and Confidential 
During the Active Phase, all subjects in the sipuleucel-T and control arms will complete: 
•  PROs/Quality of life questionnaires (Max-PC, SF-12, EPIC-CP, and IPSS) annually 
(12-, 24-, and 36-month visits) post randomization.  PROs/Quality of life questionnaires 
should be collected prior to any procedures on these specified visits. 
• Two (2) systematic biopsies (Biopsy 1 & Biopsy 2; ≥10 cores each) will be 
administered as standard of care.  Additional cores may be collected by MRI guidance 
per investigator discretion; however, MRI targeted cores collected at baseline should 
be repeated for Biopsy 1 & Biopsy 2 (Appendix 7). 
Biopsy 1 will be administered between 12 and 18 months, and Biopsy 2 will be administered 
between 33 and 39 months post randomization.  All hematoxylin and eosin (H&E) and special 
stained slides will be assessed for histopathologic grading by BICR.  Slides from each biopsy 
will be considered as a group to determine the ISUP Grade Group as opposed to any single 
slide.  The BICR is blinded to a subject’s study arm randomization.  BICR will receive the 
local pathology staining methods and Gleason score.  All subject information should be 
redacted from the local pathology reports and slides.  Local pathology reports and slides will 
be identified only by study subject number.  All slides will be returned to the clinical trial site. 
Post randomization, central pathology requested formalin-fixed paraffin-embedded (FFPE) 
tissue blocks identified by study subject number will be sent to the central pathology lab for 
cutting and slide preparation for immunohistochemistry (IHC) and genomic analysis.  All tissue 
blocks will be returned to the clinical trial site. 
Upon study completion, if the primary endpoint is met subjects on the control arm may be 
offered sipuleucel-T. 
Follow-up Phase:  
Once a subject from either the sipuleucel-T or control arms completes the end of Active Phase 
visit, they will enter the Follow-up Phase and complete Follow-up Phase visits every 6 months 
starting from their last Active Phase visit.  The Follow-up Phase visits end when the last subject 
enrolled completes Biopsy 2 and end of Active Phase visit or until the study is terminated by 
the sponsor.  All subjects will be assessed for: 
• Survival status  
• PROs/Quality of life questionnaires  
• PSA levels (as available by local laboratory) 
• Prostate cancer disease progression 
• All anti-prostate cancer therapies  
• All AEs and SAEs  

P17-1 (ProVent) Protocol 
PR-2677.02, 25 January 2019  
Page 9 of 78 
Dendreon Pharmaceuticals LLC 
 
 
Proprietary and Confidential 
AE and SAE Reporting Requirements: 
All AEs and SAEs in the sipuleucel-T arm and control arm will be collected from 
randomization through the subject’s last study visit.  AEs and SAEs will be reported and 
recorded in the subject’s medical record and entered on their eCRF.  All SAEs will also be 
reported on sponsor’s SAE Report Form. 
All AEs and SAEs reported in either the sipuleucel-T or control arms will be followed by the 
investigator until resolution, return to baseline, or the investigator determines that no further 
improvement is expected until study completion.  The start and stop dates, description, 
seriousness, toxicity, relationship to study treatment, and outcome will be recorded.  
SAEs must be reported to sponsor or designee within 24 hours of the clinical trial site’s 
awareness of the events by completing the sponsor’s SAE Report Form.  If access to the SAE 
Report Form is unavailable for any reason, the SAE information must be reported to sponsor 
or designee within 24 hours by email or facsimile and a completed written report using 
sponsor’s SAE Report form within 3 business days to:   
Dendreon Pharmaceuticals LLC 
Attention: 
DrugSafety@dendreon.com 
Significant new information regarding each SAE must be reported to sponsor or designee by 
recording the information on the SAE Report Form within 24 hours of the clinical trial site’s 
awareness of the new information and reported as noted above. 
The figure below presents a schematic of the study design. 

P17-1 (ProVent) Protocol 
PR-2677.02, 25 January 2019 
Page 10 of 78 
 
 
Dendreon Pharmaceuticals LLC 
 
 
 
 
Proprietary and Confidential 
Figure 1: Study Schematic 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
aEpstein JI, Am J Surg Pathol, 2017 
bWeeks from first infusion; Sipuleucel-T arm only; 26 wk. & 6-mo. visit may occur same day 
cMonths from randomization in both arms 
d Active Phase ends when the last subject enrolled completes 36-mo. Biopsy and end of Active Phase visit 
eInternational Society Urological Pathology (ISUP); Grade Group 1 = Gleason 3+3; Grade Group 2 = Gleason 3+4 
fImmunohistochemistry (IHC) 
 
Subjects:  
N = 450  
eISUP Grade Group 1 or 2 
Sipuleucel-T Arm 
N = 300 
(3 infusions) 
Control Arm (AS) 
N = 150 
2:1 
bWks. 0, 2, 4, 6, 10, 14, 26 
(sipuleucel-T Arm only): 
•
Immunology 
•
PCa treatment 
•
Con. meds 
•
Safety 
cEvery 6-mo. Visit: 
•
Survival 
•
PSA (Central lab) 
•
DRE 
•
PCa treatment 
•
Con. meds 
•
Immunology (sipuleucel-T only) 
•
Safety 
cEvery 12-mo Visit: 
•
PROs 
Biopsy Visits: 
•
cBiopsy 1 (12-18 mo) 
•
cBiopsy 2 (33-39 mo) 
•
 PCa treatment 
•
Con. meds 
•
Safety 
•
fIHC 
Every-6 mo. Visit: 
•
Survival 
•
PROs 
•
PSA (Local lab) 
•
PCa disease progression 
•
PCa treatment 
•
Safety 
Stratification by: 
•
a ISUP Grade Group 1 or 2 
•
Number biopsies 1 or > 1 (≤12 months of Screening) 
Final Analysis:  
Proportion of Subjects 
without ISUP Grade Group 
increase by 36 months 
R 
dActive Phase (at least 36 months) 
Follow-up Phase 

P17-1 (ProVent) Protocol 
PR-2677.02, 25 January 2019 
Page 11 of 78 
Dendreon Pharmaceuticals LLC 
 
 
Proprietary and Confidential 
Table 1: 
Schedule of Events for Subjects Randomized to Sipuleucel-T 
 
 
Item 
Screening /Baselinea 
Randomizationb 
Leukapheresis 1 
Infusion 1 (Week 0) 
Leukapheresis 2 
Infusion 2 
Leukapheresis 3 
Infusion 3 
Weeks 2, 4, 6, 10, 14, 26 
IM Visits Post 
1st Infusione 
Every 6-Month Visit 
Post Randomizatione 
Every 12-mont Visit 
Biopsy 1 & Biopsy 2 
 
End of Active Phase Visit n 
End of Active Phase and Beginning of Follow up Phaseo 
Every 6-Month 
Follow Up Visito 
Early Withdrawal Visit p 
Visit Window 
≤30 days prior 
randomization 
 
~3 days after 
leukapheresis 1 
 
~3 days after 
leukapheresis 2 
 
~3 days after 
leukapheresis 3 
± 7 days 
± 14 days 
± 14 days 
12 to 18 & 33 to 
39 months post 
randomization 
Within 1 mo. of 
Biopsy 2 
± 1 Month 
 
Informed Consent 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Prostate Biopsy  
Xc 
 
 
 
 
 
 
 
 
 
Xj 
 
 
 
Leukapheresis  
 
Xs 
 
X 
 
X 
 
 
 
 
 
 
 
 
Sipuleucel-T Infusion  
 
 
X 
 
X 
 
X 
 
 
 
 
 
 
 
Clinical Evaluations 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Demographics 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Medical History 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
  Physical Examination and Vital Signsd 
X 
X 
 
X 
 
X 
 
 
 
 
 
X 
 
X 
Digital Rectal Exam 
X 
 
 
 
 
 
 
 
X 
 
 
 
 
 
ECOG Performance Status 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Cardiovascular Risk Factorsq 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
ECG 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
AEs and SAEs 
 
X 
X 
X 
X 
X 
X 
X 
X 
 
X 
X 
X 
X 
Concomitant Medications 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
X 
X 
 
X 
Prostate Cancer Treatmenth 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
X 
X 
X 
X 
Patient Reported Outcomesi 
X 
 
 
 
 
 
 
 
 
X 
 
 
X 
X 
Survival Statusf 
 
 
 
 
 
 
 
 
X 
 
X 
X 
X 
X 

P17-1 (ProVent) Protocol 
PR-2677.02, 25 January 2019 
Page 12 of 78 
Dendreon Pharmaceuticals LLC 
 
 
Proprietary and Confidential 
 
 
Item 
Screening /Baselinea 
Randomizationb 
Leukapheresis 1 
Infusion 1 (Week 0) 
Leukapheresis 2 
Infusion 2 
Leukapheresis 3 
Infusion 3 
Weeks  2, 4, 6, 10, 14, 26 
IM Visits Post 
1’st Infusione 
Every 6-Month Visit 
Post Randomizatione 
Every 12-mont Visit 
Biopsy 1 & Biopsy 2 
 
End of Active Phase Visit n 
End of Active Phase and Beginning of Follow up Phaseo 
Every 6-Month 
Follow Up Visito 
Early Withdrawal Visit p 
Visit Window 
≤30 days prior 
randomization 
 
~3 days after 
leukapheresis 1 
 
~3 days after 
leukapheresis 2 
 
~3 days after 
leukapheresis 3 
± 7 days 
± 14 days 
± 14 days 
12 to 18 & 33 to 
39 months post 
randomization 
Within 1 mo. of 
Biopsy 2 
± 1 Month 
 
Laboratory Tests  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
IHC and Gleason Score 
Xc 
 
 
 
 
 
 
 
 
 
Xj 
 
 
 
Viral Serologym 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Chemistry and Hematology r 
X 
 
 
 
 
 
 
 
 
 
 
X 
 
X 
PSA 
Xg 
 
 
 
 
 
 
 
Xg 
 
 
 
Xt 
X 
Total Testosterone 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Immune Monitoring Sample 
Collection  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
100 mL sample l 
 
 
Xk 
 
 
 
 
Xk 
X 
 
 
 
 
 
8.5 mL sample PAXGENE RNA 
 
 
Xk 
 
 
 
 
Xk 
X 
 
 
 
 
 
2.0 mL sample PAXGENE DNA 
 
 
Xk 
 
 
 
 
 
 
 
 
 
 
 

P17-1 (ProVent) Protocol 
PR-2677.02, 25 January 2019 
Page 13 of 78 
Dendreon Pharmaceuticals LLC 
 
 
Proprietary and Confidential 
a All screening/baseline procedures must occur within 30 calendar days prior to randomization, with the exception of written informed consent and 
diagnostic biopsy. 
b Randomization is the final event of Screening once eligibility of subject is confirmed by the PI. 
c Pre-study biopsy(ies) is (are) not a study procedure and the first diagnosed biopsy must have been performed ≤12 months of signing ICF.  The biopsy 
(ies) H&E and special stained slides that were used for prostate cancer diagnosis must be submitted for BICR to determine subject eligibility. 
d Complete PE including vital signs done at the clinical site at Screening (genitourinary, skin, pulmonary, cardiovascular, neurological, gastrointestinal 
& musculoskeletal) and abbreviated PE per PI’s discretion within 7 days prior to each leukapheresis and End of Active Phase Visit. Weight will be 
measured at each PE; height will be measured at Screening only. 
e The 26-week post-first-infusion visit and first 6-month visit post randomization may occur on the same visit day and only one set of immune samples 
need to be collected if the visits fall on the same day.  
f Survival status will not be obtained for subjects that are lost to follow up or withdrawn from the study. 
g PSA should be collected prior to DRE and biopsy procedures.  
h Any prostate cancer treatment (e.g., surgery, radiation, androgen deprivation therapy). 
i Patient reported outcomes/Quality of life questionnaire (IPSS, Max-PC, SF-12 and EPIC-CP) should be collected every 12 months (12-, 24-, and 36-
month visits) prior to any procedures. 
j Biopsy 1 may take place between 12 months and 18 months post randomization.  Biopsy 2 may take place between 33 months and 39 months post 
randomization. 
k Immune monitoring sample collection time points are calculated from the date of first infusion (note: not from randomization).  Samples collected on 
infusion days (i.e., Weeks 0, 2, 4) will be drawn prior to starting the sipuleucel-T infusion.  A single PAXGENE DNA sample is only collected at 
Week 0. 
l Blood draws for immune response analyses: 100mL total draw (90ml into NaHeparin Vacutainer for PBMC isolation and 10mL into no-anticoagulant 
vacutainer tubes for serum isolation). 
m Viral serology consists of hepatitis panel (HBsAg, HBsAb, HBcAb, HCV antibody(Ab), if Ab+ then HCV RNA)), HIV-1, HIV-2 antibody screen, and 
HTLV-1, HTLV-2 antibodies 
n End-of-Active Phase visit will take place within 30 days following Biopsy 2.   
o Follow-up visits will start 6 months after the End-of-Active Phase visit.  
p The early withdrawal visit must occur within 30 days of the last visit. 
q Risk factors for cardiovascular events will include diabetes mellitus, smoking history, family history, left ventricular hypertrophy, atrial fibrillation, 
hypertension, myocardial infarction and other cardiovascular disease. 
r Chemistry and/or hematology should be completed at a local lab within 7 days of leukapheresis as requested by the Apheresis center  
s First leukapheresis will be given within 60 days of randomization 
t PSA collected per standard of care, analyzed by local lab   

P17-1 (ProVent) Protocol 
PR-2677.02, 25 January 2019 
Page 14 of 78 
Dendreon Pharmaceuticals LLC 
 
 
Proprietary and Confidential 
Table 2: 
Schedule of Events for Subjects Randomized to Control 
 
 
Item 
Screening /Baselinea 
Randomizationb 
3-Month Visit Post 
Randomizationo 
Every 6-Month Visit 
Post Randomization 
Every 12-mont Visit 
Biopsy 1 & Biopsy 2 
 
End of Active Phase 
Visit k 
End of Active Phase and Beginning of Follow up Phase l 
Every 6-Month 
Follow Up Visitl 
Early Withdrawal 
Visit m 
Visit Window 
≤30 days prior 
randomization 
± 14 days 
± 14 days 
± 14 days 
12 to 18 & 33 
to 39 months 
post 
randomization 
Within 1 mo. 
of Biopsy 2 
± 1 Month 
 
Informed Consent 
X 
 
 
 
 
 
 
 
Prostate Biopsy  
Xc 
 
 
 
Xi 
 
 
 
Clinical Evaluations 
 
 
 
 
 
 
 
 
Demographics 
X 
 
 
 
 
 
 
 
Medical History 
X 
 
 
 
 
 
 
 
  Physical Examination and Vital Signsd 
X 
 
 
 
 
X 
 
X 
Digital Rectal Exam 
X 
 
X 
 
 
 
 
 
ECOG Performance Status 
X 
 
 
 
 
 
 
 
Cardiovascular Risk Factorsn 
X 
 
 
 
 
 
 
 
ECG 
X 
 
 
 
 
 
 
 
AEs and SAEs 
 
X 
X 
 
X 
X 
X 
X 
Concomitant Medications 
X 
X 
X 
 
X 
X 
 
X 
Prostate Cancer Treatmentg 
X 
X 
X 
 
X 
X 
X 
X 
Patient Reported Outcomesh 
X 
 
 
X 
 
 
X 
X 
Survival Statuse 
 
X 
X 
 
X 
X 
X 
X 
Laboratory Tests  
 
 
 
 
 
 
 
 
IHC and Gleason Score 
Xc 
 
 
 
Xi 
 
 
 
Viral Serologyj 
X 
 
 
 
 
 
 
 
Chemistry and Hematology 
X 
 
 
 
 
X 
 
X 
PSA 
Xf 
 
Xf 
 
 
 
Xp 
X 
Total Testosterone 
X 
 
 
 
 
 
 
 

P17-1 (ProVent) Protocol 
PR-2677.02, 25 January 2019 
Page 15 of 78 
Dendreon Pharmaceuticals LLC 
 
 
Proprietary and Confidential 
a All screening/baseline procedures must occur within 30 calendar days prior to randomization, with the exception of written informed 
consent and diagnostic biopsy 
b Randomization is the final event of Screening once eligibility of subject is confirmed by the PI. 
c Pre-study biopsy(ies) is (are) not a study procedure and must have been performed ≤12 months of signing ICF.  The biopsy (ies) H&E 
and special stained slides that were used for prostate cancer diagnosis must be submitted for BICR to determine subject eligibility. 
d Complete PE including vital signs done at the clinical site at Screening (genitourinary, skin, pulmonary, cardiovascular, neurological, 
gastrointestinal & musculoskeletal) and abbreviated PE per PI’s discretion at the End of Active Phase Visit. Weight will be measured 
at each PE; height will be measured at Screening only. 
e  Survival status will not be obtained for subjects that are lost to follow up or withdrawn from the study. 
f PSA should be collected prior to DRE and biopsy procedures 
g Any prostate cancer treatment (e.g., surgery, radiation, androgen deprivation therapy) 
h Patient reported outcomes/Quality of life questionnaire (Max-PC, SF-12 EPIC-CP, and IPSS) should be collected every 12 months 
(12-, 24-, and 36-month visits) prior to any procedures on the specified visits. 
i Biopsy 1 may take place between 12 months and 18 months post randomization.  Biopsy 2 may take place between 33 months and 39 
months post randomization. 
j Viral serology consists of hepatitis panel (HBsAg, HBsAb, HBcAb, HCV antibody (Ab), if Ab+ then HCV RNA)), HIV-1, HIV-2 
antibody screen, and HTLV-1, HTLV-2 antibodies 
k End-of-Active Phase visit will take place within 30 days following Biopsy 2. 
l Follow-up visits will start 6 months after the End-of-Active Phase visit. 
m  The early withdrawal visit must occur within 30 days of the last visit. 
n  Risk factors for cardiovascular events will include diabetes mellitus, smoking history, family history, left ventricular hypertrophy, 
atrial fibrillation, hypertension, myocardial infarction and other cardiovascular disease. 
o  3-month visit may be completed in the office or via phone. 
p PSA collected per standard of care, analyzed by local lab.  
 
 
 
 
 

P17-1 (ProVent) Protocol  
PR-2677.02,  25 January2019 
Page 16 of 78 
Dendreon Pharmaceuticals LLC 
 
 
Proprietary and Confidential 
Study Population and Sample Size 
Potential subjects are men ≥18 years that have undergone prostate biopsy and diagnosed with 
adenocarcinoma of the prostate within the 12 months prior to study Screening.  Subjects 
diagnosed with either ISUP Grade Group 1 or 2 prostate cancer will undergo Screening 
procedures to ensure that they meet the inclusion and exclusion criteria.   
Subjects diagnosed with ISUP Grade Group 1 are required to have a minimum of 3 positive 
biopsy cores or one core with 50% or more cancer to be eligible for the study.   
Subjects diagnosed with ISUP Grade Group 2 will have less than 50% of total number of any 
cores positive to be eligible for the study.  See inclusion criteria 4 for further details.   
Subjects will be stratified by 1 or >1 biopsy ≤12 months prior to screening that will balance 
between arms for the number of prior biopsies and the utilization of MRI guided biopsy for a 
second or confirmatory biopsy. 
Approximately 450 eligible subjects will be randomized 2:1 to either sipuleucel-T arm or 
control arm.  ISUP Grade Group 1 will be capped at 80% of study population. 
Stratification will be based on: 
• ISUP Grade Group 1 or 2 
• Number biopsies 1 or >1 (≤12 months of Screening) 
Inclusion Criteria 
For a subject to be eligible for participation in this study, all of the following criteria must be 
satisfied. 
1. Age is ≥ 18 years  
2. Written informed consent provided prior to the initiation of study procedures 
3. Histologically proven adenocarcinoma of the prostate initially diagnosed ≤12 months of 
Screening.  All biopsy slides with subject information redacted must be submitted for BICR. 
4. Prostate cancer diagnosis determined by BICR as one of the following:  
a. ISUP Grade Group 1 with 3 or more cores positive from a systematic (≥10 cores) 
biopsy 
b. ISUP Grade Group 1 with ≥ 1 core positive with ≥50% cancer involvement from a 
systematic (≥10 cores) biopsy 

P17-1 (ProVent) Protocol  
PR-2677.02,  25 January2019 
Page 17 of 78 
Dendreon Pharmaceuticals LLC 
 
 
Proprietary and Confidential 
c. ISUP Grade Group 1 from 3 or more positive cores from any combination of cores 
from a systematic (≥10 cores) biopsy and MRI targeted biopsy (note: multiple cores 
from each MRI targeted lesion will count as 1 core) 
d. ISUP Grade Group 1 from a negative systematic (≥10 cores) biopsy and an MRI 
targeted core positive with ≥50% cancer involvement 
e. ISUP Grade Group 2 from a systematic (≥10 cores) biopsy with <50% of the total 
number of any cores positive for cancer  
f. ISUP Grade Group 2 from a negative systematic (≥10 cores) biopsy and MRI 
targeted core(s) positive for Gleason 3+4 (see note below)   
g. ISUP Grade Group 2 from any combination of cores from a systematic (≥10 cores) 
biopsy and MRI targeted biopsy (see note below) 
Note for f and g: the total number of positive cores must be <50% of total cores from both 
the systematic biopsy and MRI targeted lesions; each MRI targeted lesion, irrespective of 
multiple positive cores, will each count as 1 core for the total number of positive cores, e.g., 
4 targeted lesions with 2 positive cores each will only add 4 to the total core count.  
5. Subject consents to standard of care for biopsy frequency of 2 on-study prostate biopsies 
and to provide biopsy tissue for study endpoint analysis. 
6. Estimated life expectancy ≥ 10 years 
7. Candidate for primary curative therapy (e.g., surgery or radiation) if prostate cancer 
progression occurs 
8. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 
9. Adequate baseline hematologic, renal, and liver function tests as evidenced by laboratory 
test results within the following ranges ≤30 days prior to randomization 
• White blood cell (WBC) count  
 
≥ 3.0 x 10^6 cells/mL  
• Absolute neutrophil count (ANC) 
 
≥ 1.5 x 10^6 cells/mL  
• Platelet count  
 
 
 
≥ 1.0 x10^5 cells/µL  
• Hemoglobin (Hgb) 
 
 
 
≥ 10.0 g/dL  
• Creatinine  
 
 
 
 
≤ 1.5 mg/dL  
• Total bilirubin  
 
 
 
≤ 1.5 x upper limit of normal (ULN) 
• Alanine aminotransferase (ALT) 
 
≤ 2.0 x ULN  
• Aspartate aminotransferase (AST) 
 
≤  2.0  x ULN  
 

P17-1 (ProVent) Protocol  
PR-2677.02,  25 January2019 
Page 18 of 78 
Dendreon Pharmaceuticals LLC 
 
 
Proprietary and Confidential 
Exclusion Criteria 
A subject will not be eligible for participation in this study if any of the following criteria apply.  
1. Former therapy for prostate cancer (local or systemic) 
2. Any previous prostatic surgical procedure that significantly changes the anatomy of prostate 
(at the discretion of sponsor’s Medical Monitor)  
3. Any investigational product received for prostate cancer  
4. Prostate biopsy specimen reveals neuroendocrine or small cell features  
5. Primary Gleason score is ≥ 4 or any Gleason pattern 5  
6. Any evidence of locally advanced, regional or metastatic disease, including regional and 
distant lymph node enlargement (Nodes ≥1.5 cm in the short axis are considered pathologic 
and measurable) (Scher, 2016) 
7. A history of a cerebrovascular event (CVE) or transient ischemic attack (TIA) 
8. Subject has used a 5-alpha-reductase inhibitor (e.g., finasteride or dutasteride) continuously 
for ≥ 6 months and within 6 months prior to study Screening  
9. Subject has a history of any other stage I-IV malignancy, except for basal or squamous cell 
skin cancer.  The subject must be disease free and off any malignancy-related treatment for 
at least 5 years.  
10. Subject has prior use within 30 days of study Screening of any herbal, dietary, or alternative 
anti-cancer treatment or product, such as PC-SPES (or PC-x product), saw palmetto, 
ketoconazole, an estrogen-containing nutraceutical, or high dose calcitriol (>0.5 μg/day).  
The Investigator will consider herbal therapies on a case-by-case basis to determine whether 
they fall into the category of prohibited medications based on their potential for hormonal 
or anti-cancer or anti-cancer properties. 
11. Need for systemic chronic immunosuppressive therapy (e.g., anti-tumor necrosis factor 
alpha monoclonal antibodies, glucocorticoids)   
12. Uncontrolled, concurrent illness including, but not limited to the following: ongoing or 
active infection (bacterial, viral, or fungal), symptomatic congestive heart failure (New York 
Classification III-IV) (Appendix 6) or unstable angina pectoris within the last 6 months, or 
psychiatric illness that would limit compliance with study requirements as well as any 
condition that would preclude a subject from undergoing leukapheresis (e.g., within the 
previous 6 months: myocardial infarction, interventional cardiology procedure such as 
angioplasty or stent placement, pulmonary embolism or deep vein thrombosis).   

P17-1 (ProVent) Protocol  
PR-2677.02,  25 January2019 
Page 19 of 78 
Dendreon Pharmaceuticals LLC 
 
 
Proprietary and Confidential 
13. Hypogonadal (T < 175 ng/dL) or on continuous testosterone replacement therapy 
14. Positive serology for HIV-1, HIV-2 or HTLV-1, HTLV-2 
15. Active hepatitis B or C (See Appendix 8 and Appendix 9 for definitions) 
16. Any medical intervention, any other condition, or any other circumstance which, in the 
opinion of the investigator or the sponsor’s Medical Monitor, could compromise adherence 
with study requirements or otherwise compromise the study’s objectives. 
Statistical Considerations 
The Phase 3, open-label study is designed to assess the effects of sipuleucel-T in subjects on 
AS.  The primary endpoint will analyze approximately 450 subjects randomized (2:1 sipuleucel-
T arm versus control arm). 
It is estimated that the proportion of increased histopathologic grade reclassification over the 36 
months following randomization for the control arm will be approximately 0.30.  While there 
is no prior information on sipuleucel-T treatment response in early-stage disease available, a 
meaningful hypothesized reduction in this proportion is a reduction by 0.14, giving a projected 
outcome proportion of upgrading in the sipuleucel-T arm of 0.16.  The null hypothesis of both 
arms having a proportion of 0.70 (= 1- 0.30) being free from upgrading at 36 months versus the 
specific alternative hypothesis of a sipuleucel-T arm outcome of 0.84 (= 1- 0.16).  The odds 
ratio associated with the specific alternative hypothesis is 2.25 (sipuleucel-T arm odds over 
control arm odds).  Based on an overall 1-sided alpha of 0.025 approximately 300 subjects in 
the sipuleucel-T arm and 150 subjects in the control arm will provide 90% power to demonstrate 
the superiority of sipuleucel-T to control. 
 
 

P17-1 (ProVent) Protocol  
PR-2677.02,  25 January2019 
Page 20 of 78 
Dendreon Pharmaceuticals LLC 
 
 
Proprietary and Confidential 
TABLE OF CONTENTS 
 
PROTOCOL SYNOPSIS ................................................................................................... 3 
LIST OF ABBREVIATIONS AND TERMS ................................................................. 24 
1.0 
REGULATORY AND GOOD CLINICAL PRACTICE REQUIREMENTS 26 
1.1 
Pre-Study Documentation ........................................................................... 26 
1.2 
Institutional Review Board ......................................................................... 26 
1.3 
Investigator Obligations .............................................................................. 26 
1.4 
Informed Consent........................................................................................ 27 
1.5 
Subject Confidentiality ............................................................................... 27 
2.0 
INTRODUCTION................................................................................................. 28 
2.1 
Background ................................................................................................. 28 
2.1.1 
Prostate Cancer........................................................................... 28 
2.1.2 
Sipuleucel-T ............................................................................... 28 
3.0 
STUDY OBJECTIVES ......................................................................................... 30 
3.1 
Primary Objective ....................................................................................... 30 
3.2 
Secondary Objectives .................................................................................. 30 
3.3 
Exploratory Objectives ............................................................................... 30 
4.0 
STUDY ENDPOINTS ........................................................................................... 30 
4.1 
Primary Endpoint ........................................................................................ 30 
4.2 
Secondary Endpoints .................................................................................. 30 
4.3 
Exploratory Endpoints ................................................................................ 31 
5.0 
INVESTIGATIONAL PLAN .............................................................................. 31 
5.1 
Study Design and Duration ......................................................................... 31 
6.0 
STUDY POPULATION ....................................................................................... 37 
6.1 
Inclusion Criteria ........................................................................................ 37 
6.2 
Exclusion Criteria ....................................................................................... 39 
6.3 
Discontinuation from Study ........................................................................ 40 
6.3.1 
Discontinuation from Sipuleucel-T Arm ................................... 40 
6.3.2 
Discontinuation from Study Participation .................................. 41 
6.4 
Replacement of Subjects ............................................................................. 41 
6.5 
Lost to Follow-up ........................................................................................ 41 
6.6 
Permitted Therapies .................................................................................... 41 
6.7 
Restricted Therapies During Sipuleucel-T Treatment Period ..................... 42 
6.8 
Restricted Therapies from Randomization to End of Active Phase 
(Sipuleucel-T and Control Arms) ............................................................... 42 

P17-1 (ProVent) Protocol  
PR-2677.02,  25 January2019 
Page 21 of 78 
Dendreon Pharmaceuticals LLC 
 
 
Proprietary and Confidential 
7.0 
SIPULEUCEL-T TREATMENT ........................................................................ 43 
7.1 
Overview ..................................................................................................... 43 
7.2 
Sipuleucel-T Treatment .............................................................................. 43 
7.2.1 
Leukapheresis and Infusion Scheduling .................................... 43 
7.2.2 
Pre-leukapheresis Assessments .................................................. 43 
7.2.3 
Subject Preparation for Leukapheresis....................................... 43 
7.2.4 
Leukapheresis ............................................................................. 44 
7.2.5 
Sipuleucel-T Infusion ................................................................. 44 
7.2.6 
Sipuleucel-T Product Failures and Leukapheresis 
Rescheduling .............................................................................. 44 
7.3 
Timing of Dose for Each Subject ................................................................ 44 
7.4 
Sipuleucel-T Treatment Compliance .......................................................... 44 
7.5 
Destruction and Return of Sipuleucel-T ..................................................... 44 
8.0 
STUDY ASSESSMENTS AND PROCEDURES ............................................... 45 
8.1 
Schedule of Events for Subjects Randomized to Sipuleucel-T .................. 45 
8.2 
Informed Consent........................................................................................ 51 
8.3 
Screening..................................................................................................... 51 
8.4 
Randomization ............................................................................................ 51 
8.5 
Demographics and Medical History ........................................................... 52 
8.6 
Clinical Assessments .................................................................................. 52 
8.6.1 
Physical Examination and Vital Signs ....................................... 52 
8.6.2 
Digital Rectal Exam ................................................................... 52 
8.6.3 
Electrocardiograms .................................................................... 52 
8.6.4 
Eastern Cooperative Oncology Group Performance Status ....... 53 
8.6.5 
Cardiovascular Risk Factors ...................................................... 53 
8.6.6 
Multiparametric Magnetic Resonance Imaging (mpMRI) 
Imaging Study ............................................................................ 53 
8.7 
Patient Reported Outcomes......................................................................... 53 
8.8 
Adverse Events and Serious Adverse Events ............................................. 53 
8.9 
Concomitant Medications and Therapies .................................................... 53 
8.10 
Clinical Laboratory Tests ............................................................................ 54 
8.11 
Histopathology Assessment ........................................................................ 54 
8.12 
Immunohistochemistry Evaluations............................................................ 55 
8.13 
Sipuleucel-T Immune Monitoring Assessments ......................................... 55 
8.13.1 
Sipuleucel-T Product Parameters ............................................... 55 
8.13.2 
Sipuleucel-T Product Characterization ...................................... 55 
8.13.3 
Additional Optional Research (AOR) ........................................ 55 

P17-1 (ProVent) Protocol  
PR-2677.02,  25 January2019 
Page 22 of 78 
Dendreon Pharmaceuticals LLC 
 
 
Proprietary and Confidential 
8.13.4 
Sample Retention ....................................................................... 56 
9.0 
SAFETY ................................................................................................................. 56 
9.1 
Adverse Events ........................................................................................... 56 
9.1.1 
Definition of Adverse Event ...................................................... 56 
9.1.2 
Categories for Ranking Severity of Adverse Events.................. 57 
9.1.3 
Relationship of Adverse Events to Sipuleucel-T ....................... 57 
9.1.4 
Recording and Reporting Adverse Events ................................. 58 
9.2 
Serious Adverse Events .............................................................................. 58 
9.2.1 
Definition of Serious Adverse Event ......................................... 58 
9.2.2 
Recording and Reporting of Serious Adverse Events ................ 59 
9.2.3 
Death Reports ............................................................................. 59 
9.2.4 
Expedited Reporting Requirements ........................................... 59 
9.3 
Laboratory Test Result Abnormalities ........................................................ 60 
10.0 
STATISTICAL CONSIDERATIONS ................................................................ 60 
10.1 
Sample Size Considerations ........................................................................ 60 
10.2 
Analysis Populations ................................................................................... 61 
10.3 
Efficacy Analysis ........................................................................................ 61 
10.4 
Interim Analysis .......................................................................................... 61 
10.5 
Analysis of Study Endpoints ....................................................................... 61 
10.5.1 
Primary Endpoint ....................................................................... 61 
10.5.2 
Secondary Endpoints .................................................................. 62 
10.5.3 
Exploratory Endpoints ............................................................... 62 
10.5.4 
Biomarker Analysis .................................................................... 62 
10.5.5 
Safety ......................................................................................... 63 
10.5.6 
Other ........................................................................................... 64 
11.0 
STUDY MANAGEMENT .................................................................................... 65 
11.1 
Study Materials ........................................................................................... 65 
11.2 
Study Documentation.................................................................................. 65 
11.3 
Protocol Compliance ................................................................................... 66 
11.4 
Monitoring .................................................................................................. 66 
11.5 
Independent Data Monitoring Committee .................................................. 66 
11.6 
Quality Assurance ....................................................................................... 67 
11.7 
Steering Committee .................................................................................... 67 
11.8 
Disclosure of Data and Publication ............................................................. 67 
12.0 
REFERENCES ...................................................................................................... 68 
 

P17-1 (ProVent) Protocol  
PR-2677.02,  25 January2019 
Page 23 of 78 
Dendreon Pharmaceuticals LLC 
 
 
Proprietary and Confidential 
 
LIST OF APPENDICES 
Appendix 1: 
Eastern Cooperative Oncology Group (ECOG) Performance 
Status ............................................................................................... 70 
Appendix 2: 
Short Form-12 Health Survey (SF-12) ........................................... 71 
Appendix 3: 
Memorial Anxiety Scale for Prostate Cancer (MAX-PC) .............. 72 
Appendix 4: 
Expanded Prostate Cancer Index Composite for Clinical Practice 
(EPIC-CP) ....................................................................................... 73 
Appendix 5: 
The Internation Prostate Symptom Score (I-PSS) .......................... 74 
Appendix 6: 
New York Classification III-IV ...................................................... 75 
Appendix 7: 
Active Phase Biopsy 1 & Biopsy 2 ................................................. 76 
Appendix 8: 
Determination of Active Hepatitis B .............................................. 77 
Appendix 9: 
Determination of Active Hepatitis C .............................................. 78 
 
LIST OF TABLES 
Table 1: 
Schedule of Events for Subjects Randomized to Sipuleucel-T ...... 46 
Table 2: 
Schedule of Events for Subjects Randomized to Control ............... 49 
Table 3: 
Laboratory Tests ............................................................................. 54 
 
LIST OF FIGURES 
Figure 1: 
Study Schematic.............................................................................. 36 
 
 

P17-1 (ProVent) Protocol  
PR-2677.02,  25 January2019 
Page 24 of 78 
Dendreon Pharmaceuticals LLC 
 
 
Proprietary and Confidential 
LIST OF ABBREVIATIONS AND TERMS 
ADT 
androgen deprivation therapy 
AE 
adverse event 
ALT 
alanine aminotransferase 
AOR 
additional optional research 
APC 
antigen presenting cells 
AS 
active surveillance 
AST 
aspartate aminotransferase 
BICR 
blinded independent central review  
COI 
chain of identity  
CTCAE 
Common Terminology Criteria for Adverse Events 
CVE 
cerebrovascular event 
DRE 
digital rectal exam 
ECG 
Electrocardiogram 
ECOG  
Eastern Cooperative Oncology Group 
eCRF 
electronic case report form 
ELISA 
enzyme-linked immunosorbent assay 
EPIC-CP 
The Expanded Prostate Cancer Index Composite for Clinical Practice 
FDA 
Food and Drug Administration 
FFPE 
formalin-fixed paraffin-embedded 
GCP 
Good Clinical Practice 
GM-CSF 
granulocyte-macrophage colony-stimulating factor 
H&E 
hematoxylin and eosin 
HIV-1 
human immunodeficiency virus type 1 
HIV-2 
human immunodeficiency virus type 2 
HTLV-1 
human T-lymphotropic virus type 1  
HTLV-2 
human T-lymphotropic virus type 2  
ICF 
informed consent form 
ICH 
International Conference on Harmonization 
IHC 
Immunohistochemistry 
IMF 
immunotherapy manufacturing facility 
IND 
Investigational New Drug 
IPSS 
International Prostate Symptom Score 
IRB 
Institutional Review Board 
IRT 
Interactive Response Technology 
ISUP 
International Society of Urological Pathology 
ITT 
intent-to-treat 
mCRPC 
metastatic castration-resistant prostate cancer 
MAX-PC 
Memorial Anxiety Scale for Prostate Cancer 
mpMRI 
multiparametric magnetic resonance imaging 
OS 
overall survival 
NCI 
National Cancer Institute 
NK 
natural killer cells 
PAP 
prostatic acid phosphatase 
PA2024 
recombinant fusion protein composed PAP linked to GM-CSF 

P17-1 (ProVent) Protocol  
PR-2677.02,  25 January2019 
Page 25 of 78 
Dendreon Pharmaceuticals LLC 
 
 
Proprietary and Confidential 
PCa 
prostate cancer 
PBMC 
peripheral blood mononuclear cells 
PE 
physical examination 
PRO 
patient-reported outcome 
PSA  
prostate specific antigen 
SAE 
serious adverse event 
SF-12 
Short Form 12 Health Survey 
TIA 
transient ischemic attack  
TNC 
total nucleated cell  
ULN 
upper limit of normal 
WBC 
white blood cell 
 

P17-1 (ProVent) Protocol  
PR-2677.02,  25 January2019 
Page 26 of 78 
Dendreon Pharmaceuticals LLC 
 
 
Proprietary and Confidential 
1.0 
REGULATORY AND GOOD CLINICAL PRACTICE REQUIREMENTS 
1.1 
Pre-Study Documentation 
Prior to site activation in order for a clinical trial site to be able to start screening the first subject, 
sponsor or designee must receive: 
• Signed protocol and Investigator Brochure signature pages 
• Signed Form FDA 1572 Statement of Investigator  
• Current curriculum vitae for Investigators 
• Current medical license(s) for Investigators 
• Signed financial disclosure form from Investigators 
• Institutional Review Board (IRB) approval letter for the protocol, informed consent 
form(s) (ICFs), and materials for subject information and recruitment, as applicable 
• IRB-approved ICFs 
• IRB membership listing or Department of Health and Human Services (DHHS) 
Assurance Number 
All documentation must be updated as applicable throughout the study. 
1.2 
Institutional Review Board 
The Principal Investigator is responsible for ensuring that this protocol and relevant supporting 
information are submitted to the appropriate IRB for review and approval before the study is 
initiated.  Amendments to the protocol will also be submitted to, and approved by, the IRB prior 
to implementation of any change(s).  The Principal Investigator is also responsible for informing 
the IRB of the progress of the study and for obtaining annual IRB renewal.  The IRB must be 
informed by the Principal Investigator when the study is complete and should be provided with 
a summary of the results of the study as required by the IRB. 
1.3 
Investigator Obligations 
The Principal Investigator will ensure all clinical trial site personnel conduct the study in 
compliance with ethical principles contained within the Declaration of Helsinki, the 
International Conference on Harmonization (ICH) E6(R2) Guideline for Good Clinical Practice 
(GCP), and the Food and Drug Administration (FDA) Guidance for Industry:  Good 
Pharmacovigilance Practices and Pharmacoepidemiologic Assessment (FDA 2005).  The 
investigator will follow all national, state, and local laws. 

P17-1 (ProVent) Protocol  
PR-2677.02,  25 January2019 
Page 27 of 78 
Dendreon Pharmaceuticals LLC 
 
 
Proprietary and Confidential 
The Principal Investigator will be responsible for the subject’s compliance with the study 
protocol, and must meet periodically with the sponsor or designee’s study monitor. 
All investigators listed on Form FDA 1572 must complete financial disclosure forms (including 
information on spouses, legal partners, and/or dependent children).  Investigators must promptly 
update this information if any relevant changes occur in the course of the study or in the year 
after the study is completed.  Investigators must also complete a new financial disclosure form 
throughout the study per sponsor or designee’s requirement, regardless of whether any 
information has changed. 
In addition, the Principal Investigator is responsible for providing the sponsor or designee an 
adequate final report shortly after study participation is complete.   
1.4 
Informed Consent 
Investigators are responsible for obtaining written informed consent from subjects prior to 
initiation of any study procedures.  The investigator or an appropriately qualified delegate will 
obtain informed consent, document the steps of the informed consent process in the subject’s 
medical record, and provide a copy of the signed ICF to the subject. 
The ICF, including any amendments, must first be reviewed and approved by the sponsor or 
designee and then by the designated IRB prior to use in the study. 
If an amendment to the protocol changes the subject participation schedule in scope or activity, 
or increases the potential risk to subjects, the ICF will be revised and submitted to the IRB for 
review and approval.  The revised ICF must be used to obtain informed consent from subjects 
currently participating in the study if the information is relevant, or per the IRB’s instructions.  
The revised ICF will be used to obtain informed consent from any new subject who is enrolled 
in the study after the IRB approval date of the amendment. 
1.5 
Subject Confidentiality 
Subjects’ medical information obtained as a result of this study is considered confidential, as 
defined by applicable local, state, and federal law, and disclosure of this information to third 
parties other than those noted below is prohibited.  Subject identifiers (e.g., name, initials, or 
date of birth) will be kept confidential.  A subject’s medical information may be given to the 
subject’s personal physician or other appropriate medical personnel responsible for the subject’s 
welfare.  Data generated as a result of this study will be available for inspection on request by 
the FDA or other regulatory authorities, sponsor or its representatives, or the IRB.  Sponsor or 
designee may retain subjects’ medical information with subject identifiers redacted. 
Subject identifiers will not be collected on electronic case report forms (eCRFs) maintained by 
the sponsor or designee with the exception of date of birth and the Chain of Identity (COI) 
number of each sipuleucel-T infusion.  Subject identifiers will not be disclosed in any 
publication related to this study. 

P17-1 (ProVent) Protocol  
PR-2677.02,  25 January2019 
Page 28 of 78 
Dendreon Pharmaceuticals LLC 
 
 
Proprietary and Confidential 
Because sipuleucel-T is an autologous product, a unique COI number for each sipuleucel-T 
product must be maintained from the time of initial collection of blood during leukapheresis 
until infusion, to ensure each subject receives the correct product.  Dendreon uses a COI number 
and the subject’s full name and date of birth for this purpose.  The COI for sipuleucel-T begins 
when the subject is scheduled for sipuleucel-T infusion and is referenced during leukapheresis, 
maintained through the manufacturing process, and finally, referenced prior to infusion.  The 
COI number and subject’s full name and date of birth will be revealed to Dendreon scheduling, 
manufacturing, and leukapheresis personnel.  This disclosure is critical to ensuring subjects’ 
safety. 
2.0 
INTRODUCTION 
2.1 
Background 
2.1.1 
Prostate Cancer 
In the United States, an estimated 164,690 cases of prostate cancer will be diagnosed in 2018 
(Siegel, 2018).  However, many of these men will have disease that may never cause morbidity 
or mortality due to their diagnosis of prostate cancer.  Therefore, the management of newly 
diagnosed, localized prostate cancer detected on the basis of prostate-specific antigen (PSA) 
remains controversial.  Recently, Cooperberg et al. showed a shift from initial active treatment 
(e.g., surgery, radiation) to choosing AS (Cooperberg, 2015).  Active surveillance (AS) delays 
or indefinitely postpones the complications of surgery, radiation or androgen deprivation 
therapy (ADT), while allowing for subsequent interventional treatment with similar clinical 
efficacy associated with immediate treatment (Dall’Era, 2017).  Men on AS are advised to 
adhere to follow-up protocols and schedules (Borkhorst, 2015), yet 25% to 45% of men were 
no longer on AS after 5 to 15 years of follow-up (Klotz, 2015).  The most common reasons for 
discontinuing AS were PSA-doubling time (43.5%), grade progression (35%) patient preference 
(6%), and stage progression (3%) (Klotz, 2015).  Recently, the PRIAS study investigators 
concluded Gleason upgrading and disease re-classification (≥cT3) as the only indicators for an 
immediate switch to active treatment.  Surrogate indicators such as number of positive cores 
and a PSA-doubling time of <3 years should not trigger immediate active treatment but instead 
continued follow-up to confirm higher-risk disease (Borkhorst, 2016).  Thus histopathologic 
progression is an important indicator for prostate cancer progression and the need for treatment, 
and decreasing histopathologic progression would be a significant benefit for the AS prostate 
cancer population.  
2.1.2 
Sipuleucel-T 
Sipuleucel-T is an autologous cellular immunotherapy available as a suspension for intravenous 
infusion.  Sipuleucel-T consists of autologous peripheral blood mononuclear cells (PBMC), 
including antigen presenting cells (APCs) that have been activated during a defined culture 
period with a recombinant human protein, PAP-GM-CSF, consisting of prostatic acid 
phosphatase (PAP), an antigen expressed in prostate cancer tissue, linked to granulocyte-
macrophage colony-stimulating factor (GM-CSF), an immune cell activator.  Each dose of 

P17-1 (ProVent) Protocol  
PR-2677.02,  25 January2019 
Page 29 of 78 
Dendreon Pharmaceuticals LLC 
 
 
Proprietary and Confidential 
sipuleucel-T contains a minimum of 50 million autologous CD54+ cells activated with PAP-
GM-CSF, suspended in 250 mL of Lactated Ringer's Injection, USP. 
The active components of sipuleucel-T are autologous APCs and PAP-GM-CSF. During 
culture, the recombinant antigen binds to and is processed by APCs into smaller peptide 
fragments. The recombinant antigen is designed to target APCs, and may help direct the immune 
response to PAP.  Minimal residual levels of the intact PAP-GM-CSF are detectable in the final 
sipuleucel-T product. 
The patient's PBMCs are obtained via a standard leukapheresis procedure approximately 3 days 
prior to the infusion date.  Due to the autologous nature of sipuleucel-T, it is important that the 
patient and physician adhere to the personalized leukapheresis and infusion schedules. 
The cellular composition of sipuleucel-T is dependent on the composition of cells obtained from 
the patient's leukapheresis.  In addition to APCs, the final product contains T cells, B cells, 
natural killer (NK) cells, and other cells.  The number of cells present and the cellular 
composition of each sipuleucel-T dose will vary. 
The potency of sipuleucel-T is in part determined by measuring the increased expression of the 
CD54 molecule, also known as ICAM-1, on the surface of APCs after culture with PAP-GM-
CSF.  CD54 is a cell surface molecule that plays a role in the immunologic interactions between 
APCs and T cells, and is considered a marker of immune cell activation. 
In-process and final sterility tests are initiated prior to shipping, but the final results are not 
available for up to 7 days.  Sipuleucel-T is released for shipping based on acceptable results 
from 2-day incubation of the in-process sterility test (Sipuleucel-T, 2017). 
Sipuleucel-T induces robust and long-lived antigen-specific cellular and humoral immune 
responses that target prostate cancer cells.  The magnitude of the immune response correlates 
with overall survival (OS) in subjects with metastatic castration-resistant prostate cancer 
(mCRPC) (Sheikh, 2013). 
Sipuleucel-T administered to subjects prior to radical prostatectomy demonstrated both a 
systemic antigen-specific T cell response and a local response with the recruitment of activated 
effector T cells into the prostate tumor microenvironment (Fong, 2014).  In subjects with non-
metastatic hormone-sensitive prostate cancer, the magnitude of immunoglobulin G responses 
to antigen was significantly higher, and the magnitude of secondary antibody responses (antigen 
spread), as well as APC activation was significantly greater when compared to subjects with 
mCRPC (Antonarakis, 2017).  These data suggest sipuleucel-T may have a more robust anti-
cancer effect in non-metastatic hormone-sensitive prostate cancer subjects and the potential to 
slow or inhibit the development of more aggressive disease requiring treatment for men on AS. 
The purpose of this study is to determine if sipuleucel-T will decrease the development of 
histopathologic progression upon subsequent prostate biopsies for subjects on AS.  

P17-1 (ProVent) Protocol  
PR-2677.02,  25 January2019 
Page 30 of 78 
Dendreon Pharmaceuticals LLC 
 
 
Proprietary and Confidential 
3.0 
STUDY OBJECTIVES 
3.1 
Primary Objective 
• To assess the efficacy of sipuleucel-T in reducing histopathologic reclassification to a 
higher Gleason grade in prostate cancer subjects on active surveillance (AS) 
3.2 
Secondary Objectives 
• To assess the differential receipt of local or systemic therapy (surgery, radiation, ADT) 
in each study arm, and the reasons for receipt of further local or systemic therapy  
• To assess differences in quality of life (i.e., patient-reported outcomes (PRO)) between 
sipuleucel-T and control arms 
• To evaluate the safety of sipuleucel-T in men with low to intermediate risk localized 
prostate cancer 
3.3 
Exploratory Objectives 
• To evaluate in the sipuleucel-T arm the association of peripheral blood and tumor 
microenvironment immunologic responses with reclassification of Gleason grade over 
time  
• To evaluate clinical assessments and potential correlation to sipuleucel-T 
• To evaluate prostate tissue genomics 
4.0 
STUDY ENDPOINTS 
4.1 
Primary Endpoint 
• Proportion of subjects without histological reclassification (Gleason group upgrade) 
within 36 months of randomization as determined by Blinded Independent Central 
Review (BICR)  
o Upgrade is defined as subjects at randomization with either International Society of 
Urological Pathology (ISUP) Grade Group 1 (Gleason 3+3) upgraded to Grade 
Group 2 (Gleason 3+4) or higher or subjects at randomization with Grade Group 2 
upgraded to Grade Group 3 (Gleason 4+3) or higher. 
4.2 
Secondary Endpoints 
• To determine the number of subjects with subsequent prostate cancer treatment (e.g., 
surgery, radiation, ADT) in each study arm 
• Characterization of PROs by Memorial Anxiety Scale for Prostate Cancer (MAX-PC), 
Short Form 12 Health Survey (SF-12), The Expanded Prostate Cancer Index Composite 

P17-1 (ProVent) Protocol  
PR-2677.02,  25 January2019 
Page 31 of 78 
Dendreon Pharmaceuticals LLC 
 
 
Proprietary and Confidential 
for Clinical Practice (EPIC-CP), International Prostate Symptom Score (IPSS) at 
baseline and 12-, 24-, and 36-month visits after randomization 
• To evaluate safety by determining the incidence of adverse events (AEs), assessing 
laboratory data for clinically significant laboratory abnormalities and evaluating 
physical examination (PE) findings in each study arm  
4.3 
Exploratory Endpoints 
• To calculate the correlation of prostate tissue and peripheral immune responses as well 
as product parameters to sipuleucel-T efficacy 
• To determine in the cohort of subjects having a radical prostatectomy the number 
subjects with an ISUP Grade Group change (up- or down-grade) determined by BICR 
from radical prostatectomy tissue histology in each study arm 
• To measure the percentage of subjects with a negative biopsy at any post- randomization 
biopsy assessment in each study arm 
• To compare the proportion of subjects with clinical risk group progression (e.g., Cancer 
of the Prostate Risk Assessment (CAPRA) and National Comprehensive Cancer 
Network (NCCN) prostate cancer risk groups) between study arms 
• To calculate Prostate-specific antigen (PSA) velocity from randomization through study 
completion in each study arm  
• To determine the association of prostate cancer tissue genomic profile and sipuleucel-T 
treatment 
5.0 
INVESTIGATIONAL PLAN 
5.1 
 Study Design and Duration 
This is a multicenter, randomized, open-label study of immunotherapy with sipuleucel-T 
compared to control subjects followed on AS.  The study will enroll subjects being followed by 
AS and initially diagnosed within 12 months prior to Screening with either ISUP Grade Group 
1 or 2 adenocarcinoma of the prostate.  
This study consists of 3 phases (see Section 8.0 for more details): 
Screening Phase:  
The Screening Phase will begin at the completion of the informed consent process and continues 
until randomization.  Screening procedures will be performed up to 30 days prior to 
randomization. 
 

P17-1 (ProVent) Protocol  
PR-2677.02,  25 January2019 
Page 32 of 78 
Dendreon Pharmaceuticals LLC 
 
 
Proprietary and Confidential 
The following assessments will be performed on all subjects during the Screening Phase:  
• BICR of prostate biopsy slides obtained from local pathologist (ISUP Grade Group and 
Gleason Score) 
• Clinical evaluations (demographics, medical history, PE & vital signs, digital rectal 
examination (DRE), Eastern Cooperative Oncology Group (ECOG) performance status, 
cardiovascular risk assessment & electrocardiogram (ECG)) 
• Cardiovascular  and thrombosis disease history 
• Concomitant medications 
• All anti-prostate cancer therapies 
• PROs/Quality of life questionnaires  
• Virology serology (HBsAg, HBsAb, HBcAb, HCV antibody(Ab), if Ab positive (Ab+) 
then HCV RNA)), HIV-1 and HIV-2 antibody screen and HTLV-1, HTLV-2 antibodies 
• Hematology and chemistry 
• PSA 
• Total testosterone 
Active Phase:  
The Active Phase will begin at randomization and continues through completion of the end of 
Active Phase study visit (within 30 days of Biopsy 2) or until the study is terminated by the 
sponsor.  Subjects who withdraw consent and discontinue from the study prior completing end 
of Active Phase study visit will undergo an Early Withdrawal visit within 30 days following 
discontinuation notice (Section 6.3).  Subjects are encouraged to have, as standard of care, a 
systematic prostate biopsy (≥10 cores) with or without MRI at the investigator’s discretion prior 
to study withdrawal.  The H&E and special-stained slides from this biopsy will be submitted 
for  BICR determination of their ISUP Grade Group classification prior to study withdrawal  
After Screening assessments are completed, eligible subjects will be randomized 2:1 to the 
sipuleucel-T arm or the control arm.  Subjects randomized to sipuleucel-T arm will undergo 
their first leukapheresis within 60 days of randomization and will receive 3 infusions of 
sipuleucel-T at approximately 2-week intervals.  Subjects randomized to the control arm will 
be followed on AS as described in the schedule of events (Table 2).  
 

P17-1 (ProVent) Protocol  
PR-2677.02,  25 January2019 
Page 33 of 78 
Dendreon Pharmaceuticals LLC 
 
 
Proprietary and Confidential 
Subjects randomized to the sipuleucel-T arm will be evaluated at 0, 2, 4, 6, 10, 14, and 26 weeks 
following the first infusion for: 
• Immune responses (Week 0 prior to first infusion is baseline) 
• All anti-prostate cancer therapies 
• Concomitant medications 
• Adverse events (AEs) and serious adverse events (SAEs) (per reporting requirements 
for the sipuleucel-T arm) (Section 9)  
Subjects randomized to the control arm will be evaluated (office visit or phone) at 3 months 
following randomization for:  
• Survival status  
• All anti-prostate cancer therapies 
• Concomitant medications 
• All AEs and SAEs  
Subsequently, all subjects in the sipuleucel-T and control arms will be followed every 6 months 
from date of randomization for at least 36 months for: 
• Immune responses (sipuleucel-T arm only) 
• Survival status  
• PSA levels (should be collected prior to DRE and biopsy procedures) 
• DRE assessments 
• Prostate cancer disease progression 
• All anti-prostate cancer therapies  
• Concomitant medications 
• All AEs and SAEs  
Note, for subjects randomized to the sipuleucel-T arm, scheduled events for the 26-week visit 
post first infusion and first 6-month visit post randomization may take place on the same visit 
and only one set of immune samples need to be collected. 
 

P17-1 (ProVent) Protocol  
PR-2677.02,  25 January2019 
Page 34 of 78 
Dendreon Pharmaceuticals LLC 
 
 
Proprietary and Confidential 
During the Active Phase, all subjects in the sipuleucel-T and control arms will complete: 
•  PROs/Quality of life questionnaires (Max-PC, SF-12, EPIC-CP, and IPSS) annually 
(12-, 24-, and 36-month visits) post randomization.  PROs/Quality of life questionnaires 
should be collected prior to any procedures on these specified visits. 
• Two (2) systematic biopsies (Biopsy 1 & Biopsy 2; ≥10 cores each)) will be 
administered as standard of care. Additional cores may be collected by MRI guidance 
per investigator discretion; however, MRI targeted cores collected at baseline should be 
repeated for Biopsy 1 & Biopsy 2 (Appendix 7). 
Biopsy 1 will be administered between 12 and 18 months, and Biopsy 2 will be administered 
between 33 and 39 months post randomization.  All hematoxylin and eosin (H&E) and special 
stained slides will be assessed for histopathologic grading by BICR. Slides from each biopsy 
will be considered as a group to determine the ISUP Grade Group as opposed to any single 
slide.   The BICR is blinded to a subject’s study arm randomization.  BICR will receive the local 
pathology staining methods and Gleason score.  All subject information should be redacted from 
the local pathology reports and slides.  Local pathology reports and slides will be identified only 
by study subject number.  All slides will be returned to the clinical trial site. 
Post randomization, central pathology requested formalin-fixed paraffin-embedded (FFPE) 
tissue blocks identified by study subject number will be sent to the central pathology lab for 
cutting and slide preparation for immunohistochemistry (IHC) and genomic analysis.  All tissue 
blocks will be returned to the clinical trial site. 
Follow-up Phase:  
Once a subject from either the sipuleucel-T or control arms completes the end of Active Phase 
visit, they will enter into Follow-up Phase and will complete Follow-up Phase visits every 6 
months starting from their last Active Phase visit.  The Follow-up Phase end when the last 
subject enrolled completes Biopsy 2 and end of Active Phase visit or until the study is 
terminated by the sponsor. All subjects will be assessed for: 
• Survival status 
• PROs/Quality of life questionnaires  
• PSA levels (as available by local laboratory) 
• Prostate cancer disease progression 
• All anti-prostate cancer therapies  
• AEs and SAEs (per reporting requirements for each arm; Section 9) 

P17-1 (ProVent) Protocol  
PR-2677.02,  25 January2019 
Page 35 of 78 
Dendreon Pharmaceuticals LLC 
 
 
Proprietary and Confidential 
Upon completion of the study, if the primary endpoint is met, subjects on the control arm may 
be offered sipuleucel-T. 

P17-1 (ProVent) Protocol  
PR-2677.02, 25 January 2019 
Page 36 of 78 
Dendreon Pharmaceuticals LLC 
 
 
Proprietary and Confidential 
The figure below presents a schematic of the study design. 
Figure 1: 
Study Schematic 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
aEpstein JI, Am J Surg Pathol, 2017 
bWeeks from first infusion; Sipuleucel-T arm only; 26 wk. & 6-mo. visit may occur same 
day 
cMonths from randomization in both arms 
d Active Phase ends when the last subject enrolled completes 36-mo. Biopsy and end of 
Active Phase visit 
eInternational Society Urological Pathology (ISUP); Grade Group 1 = Gleason 3+3; Grade 
Group 2 = Gleason 3+4 
fImmunohistochemistry (IHC) 
 
Subjects:  
N = 450  
eISUP Grade Group 1 or 2 
Sipuleucel-T Arm 
N = 300 
(3 infusions) 
Control Arm (AS) 
N = 150 
2:1 
bWks. 0, 2, 4, 6, 10, 14, 26 
(sipuleucel-T Arm only): 
•
Immunology 
•
PCa treatment 
•
Con. meds 
•
Safety 
cEvery 6-mo. Visit: 
•
Survival 
•
PSA (Central lab) 
•
DRE 
•
PCa treatment 
•
Con. meds 
•
Immunology (sipuleucel-T only) 
•
Safety 
cEvery 12-mo Visit: 
•
PROs 
Biopsy Visits: 
•
cBiopsy 1 (12-18 mo) 
•
cBiopsy 2 (33-39 mo) 
•
 PCa treatment 
•
Con. meds 
•
Safety 
•
fIHC 
Every-6 mo. Visit: 
•
Survival 
•
PROs 
•
PSA (Local lab) 
•
PCa disease progression 
•
PCa treatment 
•
Safety 
Stratification by: 
•
a ISUP Grade Group 1 or 2 
•
Number biopsies 1 or > 1 (≤12 months of Screening) 
Final Analysis:  
Proportion of Subjects 
without ISUP Grade Group 
increase by 36 months 
R 
dActive Phase (at least 36 months) 
Follow-up Phase 

P17-1 (ProVent) Protocol  
PR-2677.02, 25 January 2019 
Page 37 of 78 
Dendreon Pharmaceuticals LLC 
 
 
Proprietary and Confidential 
6.0 
STUDY POPULATION 
Potential subjects are men ≥18 years that have undergone prostate biopsy and diagnosed with 
adenocarcinoma of the prostate within 12 months prior to study Screening.  Subjects diagnosed 
with either ISUP Grade Group 1 or 2 prostate cancer will undergo screening procedures to 
ensure that they meet the inclusion and exclusion criteria.   
Subjects diagnosed with ISUP Grade Group 1 are required to have a minimum of 3 positive 
biopsy cores or one core with 50% or more cancer to be eligible for the study.   
Subjects diagnosed with ISUP Grade Group 2 will have less than 50% of total number of any 
cores positive to be eligible for the study.  See inclusion criteria 4 for further details.   
Subjects will be stratified by 1 or >1 biopsy ≤12 months prior to screening that will balance 
between arms for the number of prior biopsies and the utilization of MRI guided biopsy for a 
second or confirmatory biopsy. 
Approximately 450 eligible subjects will be randomized 2:1 to either sipuleucel-T arm or 
control arm.  ISUP Grade Group 1 will be capped at 80% of study population. 
Stratification will be based on: 
• ISUP Grade Group 1 or 2 
• Number biopsies 1 or >1 (≤12 months of Screening) 
6.1 
Inclusion Criteria 
For a subject to be eligible for participation in this study, all of the following criteria must be 
satisfied. 
6.1.1. Age is ≥ 18 years  
6.1.2. Written informed consent provided prior to the initiation of study procedures 
6.1.3. Histologically proven adenocarcinoma of the prostate initially diagnosed ≤12 months of 
Screening.  All biopsy slides with subject information redacted must be submitted for 
BICR. 
6.1.4. Prostate cancer diagnosis determined by BICR as one of the following:  
a. ISUP Grade Group 1 with 3 or more cores positive from a systemic (≥10 cores)  
biopsy. 
b. ISUP Grade Group 1 with ≥1 core positive with ≥50% cancer involvement from a 
systematic (≥10 cores) biopsy 

P17-1 (ProVent) Protocol  
PR-2677.02, 25 January 2019 
Page 38 of 78 
Dendreon Pharmaceuticals LLC 
 
 
Proprietary and Confidential 
c. ISUP Grade Group 1 from 3 or more positive cores from any combination of cores 
from a systematic (≥10 cores) biopsy and MRI targeted biopsy (note: multiple cores 
from each MRI targeted lesion will count as 1 core) 
d. ISUP Grade Group 1 from a negative systematic (≥10 cores) biopsy and an MRI 
targeted core positive with ≥50% cancer involvement 
e. ISUP Grade Group 2 from a systematic (≥10 cores) biopsy (with<50% of the total 
number of any cores positive for cancer  
f. ISUP Grade Group 2 from a negative systematic (≥10 cores) biopsy and MRI 
targeted core(s) positive for Gleason 3+4 (see note below) 
g. ISUP Grade Group 2 from any combination of cores from a systematic (≥10 cores) 
biopsy and MRI targeted biopsy (see note below) 
Note for f and g: the total number of positive cores must be <50% of total cores from 
both the systematic biopsy and MRI targeted lesions; each MRI targeted lesion, 
irrespective of multiple positive cores, will each count as 1 core for the total number of 
positive cores, e.g., 4 targeted lesions with 2 positive cores each will only add 4 to the 
total core count).Subject consents to standard of care for biopsy frequency of 2 on-study 
prostate biopsies and to provide biopsy tissue for study endpoint analysis. 
6.1.5. Estimated life expectancy ≥ 10 years 
6.1.6. Candidate for primary curative therapy (e.g., surgery or radiation) if prostate cancer 
progression occurs 
6.1.7. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 
6.1.8. Adequate baseline hematologic, renal, and liver function tests as evidenced by 
laboratory test results within the following ranges ≤30 days prior to randomization 
• White blood cell (WBC) count  
 
≥ 3.0 x 10^6 cells/mL  
• Absolute neutrophil count (ANC) 
 
≥ 1.5 x 10^6 cells/mL  
• Platelet count  
 
 
 
≥ 1.0 x10^5 cells/µL  
• Hemoglobin (Hgb) 
 
 
 
≥ 10.0 g/dL  
• Creatinine  
 
 
 
 
≤ 1.5 mg/dL  
• Total bilirubin  
 
 
 
≤ 1.5 x upper limit of normal (ULN) 
• Alanine aminotransferase (ALT) 
 
≤ 2.0 x ULN  
• Aspartate aminotransferase (AST) 
 
≤ 2.0 x ULN  
 
 

P17-1 (ProVent) Protocol  
PR-2677.02, 25 January 2019 
Page 39 of 78 
Dendreon Pharmaceuticals LLC 
 
 
Proprietary and Confidential 
6.2 
Exclusion Criteria 
A subject will not be eligible for participation in this study if any of the following criteria apply.  
6.2.1. Former therapy for prostate cancer (local or systemic) 
6.2.2. Any previous prostatic surgical procedure that significantly changes the anatomy of 
prostate (at the discretion of sponsor’s Medical Monitor)  
6.2.3. Any investigational product received for prostate cancer  
6.2.4. Prostate biopsy specimen reveals neuroendocrine or small cell features  
6.2.5. Primary Gleason score is ≥ 4 or any Gleason pattern 5  
6.2.6. Any evidence of locally advanced, regional or metastatic disease, including regional and 
distant lymph node enlargement (Nodes ≥1.5 cm in the short axis are considered 
pathologic and measurable) (Scher, 2016) 
6.2.7. A history of a cerebrovascular event (CVE) or transient ischemic attack (TIA) 
6.2.8. Subject has used a 5-alpha-reductase inhibitor (e.g., finasteride or dutasteride) 
continuously for ≥ 6 months and within 6 months prior to study Screening  
6.2.9. Subject has a history of any other stage I-IV malignancy, except for basal or squamous 
cell skin cancer.  The subject must be disease free and off any malignancy-related 
treatment for at least 5 years.  
6.2.10. Subject has prior use within 30 days of study Screening of any herbal, dietary, or 
alternative anti-cancer treatment or product, such as PC-SPES (or PC-x product), saw 
palmetto, ketoconazole, an estrogen-containing nutraceutical, or high dose calcitriol 
(>0.5 μg/day).  The Investigator will consider herbal therapies on a case-by-case basis 
to determine whether they fall into the category of prohibited medications based on their 
potential for hormonal or anti-cancer or anti-cancer properties.  
6.2.11. Need for systemic chronic immunosuppressive therapy (e.g., anti-tumor necrosis factor 
alpha monoclonal antibodies, glucocorticoids)   
6.2.12. Uncontrolled, concurrent illness including, but not limited to the following: ongoing or 
active infection (bacterial, viral, or fungal), symptomatic congestive heart failure (New 
York Classification III-IV) (Appendix 6) or unstable angina pectoris within the last 6 
months, or psychiatric illness that would limit compliance with study requirements as 
well as any condition that would preclude a subject from undergoing leukapheresis (e.g., 
within the previous 6 months: myocardial infarction, interventional cardiology 
procedure such as angioplasty or stent placement, pulmonary embolism or deep vein 
thrombosis).   

P17-1 (ProVent) Protocol  
PR-2677.02, 25 January 2019 
Page 40 of 78 
Dendreon Pharmaceuticals LLC 
 
 
Proprietary and Confidential 
6.2.13. Hypogonadal (T < 175 ng/dL) or on continuous testosterone replacement therapy 
6.2.14. Positive serology for HIV-1, HIV-2 or HTLV-1, HTLV-2 
6.2.15. Active hepatitis B or C (See Appendix 8 and Appendix 9 for definitions) 
6.2.16. Any medical intervention, any other condition, or any other circumstance which, in the 
opinion of the investigator or the sponsor’s Medical Monitor, could compromise 
adherence with study requirements or otherwise compromise the study’s objectives. 
6.3 
Discontinuation from Study  
A subject may discontinue participation in the trial at any time without prejudice.  If a subject 
withdraws consent for any further study involvement, complete withdrawal of consent must be 
documented in the subject’s medical record.  The date and reason for withdrawal will be 
recorded in the subject’s medical record and on the eCRF. 
Whenever possible, every subject who withdraws consent and discontinues from the study will 
undergo an Early Withdrawal Visit within 30 days following discontinuation notice.  Subjects 
are encouraged to have, as standard of care, a systematic prostate biopsy (≥10 cores) with or 
without MRI at the investigator’s discretion prior to study withdrawal.  The H&E and special-
stained slides from this biopsy will be submitted for BICR determination of their ISUP Grade 
Group classification prior to study withdrawal.  All AEs considered by the investigator to be 
related to sipuleucel-T that are ongoing at the time of discontinuation will be followed by the 
investigator until resolution, return to baseline, or a determination by the investigator that no 
further improvement is expected.  The investigator should make every reasonable attempt to 
ensure that the subject is contacted (via telephone or during the Early Withdrawal Visit) to 
obtain the final status of any AEs and concomitant medications. 
6.3.1 
Discontinuation from Sipuleucel-T Arm 
Declining the first sipuleucel-T infusion or associated leukapheresis will result in an automatic 
withdrawal from the study.  Subjects will complete an early withdraw visit within 30 days of 
the scheduled sipuleucel-T infusion. 
Sipuleucel-T will be discontinued if a subject meets any of the following criteria: 
• The subject never undergoes a leukapheresis for the purpose of receiving sipuleucel-T 
• The subject undergoes leukapheresis, but is unable to receive at least 1 partial (>0 mL) 
sipuleucel-T infusion for any reason at the discretion of sponsor’s Medical Monitor 
• Inability to manufacture sipuleucel-T in the opinion of the sponsor’s medical monitor  
• The subject experiences intolerable toxicity  
• Significant infection at the discretion of sponsor’s Medical Monitor  

P17-1 (ProVent) Protocol  
PR-2677.02, 25 January 2019 
Page 41 of 78 
Dendreon Pharmaceuticals LLC 
 
 
Proprietary and Confidential 
• CVE or TIA of any grade prior to completion of 3 sipuleucel-T infusions 
• Withdrawal of consent for continued sipuleucel-T infusions 
• The subject fails to comply with protocol-specified procedures or protocol requirements 
• Sponsor terminates the study 
• The subject is discontinued from the study at the discretion of the investigator or sponsor 
6.3.2 
Discontinuation from Study Participation 
A subject in either the sipuleucel-T or control study arms will end study participation, including 
discontinuation of sipuleucel-T (sipuleucel-T arm only), biopsy and blood sample collection, 
for any of the following reasons: 
• The subject withdraws consent or loses the ability to provide informed consent to 
participate in the study for any reason 
• The subject is diagnosed with locally advanced or metastatic prostate cancer 
• The subject dies or is lost to follow-up (Section 6.5) 
6.4 
Replacement of Subjects  
Subjects who are randomized to the sipuleucel-T arm, but do not receive any sipuleucel-T (>0 
mL) may be replaced. 
6.5 
Lost to Follow-up 
If a subject fails to respond to requests for follow-up, the clinical trial site will send a certified 
letter, at a minimum, to the subject requesting contact with the clinic.  All attempts to resume 
contact (including copies of written correspondence) will be included in the subject's medical 
record.  Subjects who do not respond to requests for follow-up after all the above attempts to 
establish contact will be considered lost to follow-up.   
6.6 
Permitted Therapies 
Subjects should receive full supportive care in accordance with standard practice at the clinical 
trial site. 
Subjects who are receiving non-prostate cancer therapies (prescription or over-the-counter) at 
the time of randomization (that are not restricted (Section 6.7) should continue per the discretion 
of the prescribing physician.  

P17-1 (ProVent) Protocol  
PR-2677.02, 25 January 2019 
Page 42 of 78 
Dendreon Pharmaceuticals LLC 
 
 
Proprietary and Confidential 
6.7 
Restricted Therapies During Sipuleucel-T Treatment Period 
Certain therapies and procedures could confound the results of this study.  Therefore, subjects 
who are randomized to the sipuleucel-T arm and receive any of the following, 30 days prior to 
the first infusion until 30 days after the last infusion, will discontinue sipuleucel-T treatment 
(Section 6.3.1): 
• Any immunosuppressive therapy, including systemic steroids.  Use of inhaled, intra-
nasal, intra-articular, and topical steroids is allowed.  Oral or IV steroids to prevent or 
treat IV contrast reactions are allowed 
• Blood products 
• GM-CSF or G-CSF 
• Any vaccinations  
Subjects that discontinue sipuleucel-T treatment and have received > 0 mL of sipuleucel-T will 
remain in the Active Phase and follow the schedule of events (Table 1).   
6.8 
Restricted Therapies from Randomization to End of Active Phase (Sipuleucel-T 
and Control Arms) 
Certain therapies and procedures could confound the results of this study.  Therefore, subjects 
who receive any of the following will go from Active Phase of the study to the Follow-up Phase 
of the study: 
• Any local or systemic therapy or procedures for prostate cancer (e.g., ADT, radical 
prostatectomy, external beam radiation or brachytherapy) 
• Any local or systemic therapy or procedure targeting the prostate (e.g., transurethral 
resection of the prostate (TURP) or 5-alpha reductase inhibitor) 
• Major surgery at the discretion of the sponsor’s Medical Monitor 
• Any investigational product for prostate cancer or other condition (per sponsor’s 
Medical Monitor approval) 
• Any other therapy at the discretion of the sponsor’s Medical Monitor 
 
 

P17-1 (ProVent) Protocol  
PR-2677.02, 25 January 2019 
Page 43 of 78 
Dendreon Pharmaceuticals LLC 
 
 
Proprietary and Confidential 
7.0 
SIPULEUCEL-T TREATMENT 
7.1 
Overview 
Dendreon will supply sipuleucel-T that must be stored, handled, prepared, administered, and 
labeled as specified by the current version of the sipuleucel-T Investigator’s Brochure. 
Accountability documentation must be maintained to ensure that sipuleucel-T is accurately 
administered.  Such documentation will note request, shipment, receipt, storage, dispensation, 
administration, destruction, return, and use of required processes. 
7.2 
Sipuleucel-T Treatment 
7.2.1 
Leukapheresis and Infusion Scheduling 
Once a subject has completed screening assessments and has been confirmed to be eligible and 
randomized to the sipuleucel-T arm, Dendreon will designate a leukapheresis center and the site 
will request a schedule for the subject’s leukapheresis procedures to occur at approximately 2-
week intervals.  The date of each leukapheresis procedure will determine the date for the 
subsequent infusion of sipuleucel-T (approximately 3 days later). 
The clinical trial site will receive confirmation of the leukapheresis and infusion dates and will 
schedule the subject’s infusion appointments accordingly.  If the subject is subsequently deemed 
ineligible for the study, the clinical trial site will be informed and the leukapheresis and infusion 
appointments will be canceled. 
7.2.2 
Pre-leukapheresis Assessments 
Prior to each leukapheresis, subjects will undergo a pre-leukapheresis assessment to determine 
their suitability for the leukapheresis procedure.  The pre-leukapheresis assessments including 
any requested tests by the apheresis center should be done within 7 days prior to each 
leukapheresis. 
If a subject has any infection requiring parenteral antibiotic therapy or causing fever 
(temperature > 100.5°F or > 38.1°C) within  7 days prior to a leukapheresis appointment, the 
appointment should be rescheduled to occur after the fever resolves and the investigator believes 
the subject is healthy enough to undergo the procedure. 
7.2.3 
Subject Preparation for Leukapheresis 
The subject should be instructed to eat calcium-rich foods in advance of the leukapheresis 
procedure.  The subject should also be instructed to drink plenty of fluids a few days prior to 
the procedure to promote adequate venous access during leukapheresis, but to avoid drinking 
caffeinated beverages on the day of each leukapheresis procedure. 

P17-1 (ProVent) Protocol  
PR-2677.02, 25 January 2019 
Page 44 of 78 
Dendreon Pharmaceuticals LLC 
 
 
Proprietary and Confidential 
7.2.4 
Leukapheresis 
To manufacture of one dose of sipuleucel-T, the subject will undergo leukapheresis in order to 
collect PBMC.  All PBMC collected from one leukapheresis procedure will be used to produce 
one dose of sipuleucel-T.  Immediately after completion of the leukapheresis procedure, the 
PBMC are transported to a Dendreon immunotherapy manufacturing facility (IMF). 
7.2.5 
Sipuleucel-T Infusion 
Each sipuleucel-T product is released by Dendreon for infusion approximately 3 days after the 
leukapheresis procedure.    The clinical trial site will provide all supplies required for infusion. 
Sipuleucel-T must be administered under the supervision of an investigator experienced in the 
medical treatment of prostate cancer and in an environment where resuscitation equipment is 
available. 
7.2.6 
Sipuleucel-T Product Failures and Leukapheresis Rescheduling 
A subject may be scheduled for a repeat leukapheresis procedure if the subject’s leukapheresis 
procedure fails, sipuleucel-T does not meet quality release specifications, sipuleucel-T infusion 
is not started prior to its expiration, or for various other reasons.  Rescheduling will depend 
upon the capacities of the leukapheresis center and the Dendreon IMF, and ≥ 2 weeks should 
elapse between one leukapheresis procedure and the next (1-week interval may be approved at 
the discretion of the Medical Monitor). 
If a subject’s subsequent leukapheresis procedure is delayed or rescheduled for any reason, all 
protocol-specified pre-leukapheresis assessment conditions apply.  
In rare instances, it may be determined for a given subject that it is not possible to manufacture 
sipuleucel-T that meets manufacturing release specifications (Section 6.3.1). 
7.3 
Timing of Dose for Each Subject 
Subjects will receive 3 infusions of sipuleucel-T at approximately 2 week intervals.  Each dose 
of sipuleucel-T contains a minimum of 50 million autologous CD54+ cells activated with 
recombinant fusion protein composed PAP linked to GM-CSF (PA2024).   
7.4 
Sipuleucel-T Treatment Compliance 
Sipuleucel-T treatment compliance is evaluated by each site’s clinical trial infusion personnel. 
7.5 
Destruction and Return of Sipuleucel-T 
Clinical trial site personnel will dispose of sipuleucel-T bags and tubing according to 
institutional procedures for disposal of biohazardous waste that contains human blood.  All 
sipuleucel-T packaging materials and gel packs will be disposed of according to institutional 
procedures. 

P17-1 (ProVent) Protocol  
PR-2677.02, 25 January 2019 
Page 45 of 78 
Dendreon Pharmaceuticals LLC 
 
 
Proprietary and Confidential 
If instructed by Dendreon to return the remaining sipuleucel-T, tubing, or both, clinical trial site 
personnel will place these items in the original shipping box with the original packaging 
materials and ship them according to Dendreon’s instructions. 
8.0 
STUDY ASSESSMENTS AND PROCEDURES 
8.1 
Schedule of Events for Subjects Randomized to Sipuleucel-T  
The Schedule of Events for subjects randomized to sipuleucel-T is presented in Table 1.  

P17-1 (ProVent) Protocol  
PR-2677.02, 25 January 2019  
Page 46 of 78 
Dendreon Pharmaceuticals LLC 
 
 
Proprietary and Confidential 
Table 1: 
Schedule of Events for Subjects Randomized to Sipuleucel-T 
 
 
Item 
Screening /Baselinea 
Randomizationb 
Leukapheresis 1 
Infusion 1 (Week 0) 
Leukapheresis 2 
Infusion 2 
Leukapheresis 3 
Infusion 3 
Weeks  2, 4, 6, 10, 14, 26 
IM Visits Post 
1’st Infusione 
Every 6-Month Visit 
Post Randomizatione 
Every 12-mont Visit 
Biopsy 1 & Biopsy 2 
 
End of Active Phase Visit n 
End of Active Phase and Beginning of Follow up Phaseo 
Every 6-Month 
Follow Up Visito 
Early Withdrawal Visit p 
Visit Window 
≤30 days prior 
randomization 
 
~3 days after 
leukapheresis 1 
 
~3 days after 
leukapheresis 2 
 
~3 days after 
leukapheresis 3 
± 7 days 
± 14 days 
± 14 days 
12 to 18 & 33 to 
39 months post 
randomization 
Within 1 mo. of 
Biopsy 2 
± 1 Month 
 
Informed Consent 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Prostate Biopsy  
Xc 
 
 
 
 
 
 
 
 
 
Xj 
 
 
 
Leukapheresis  
 
Xs 
 
X 
 
X 
 
 
 
 
 
 
 
 
Sipuleucel-T Infusion  
 
 
X 
 
X 
 
X 
 
 
 
 
 
 
 
Clinical Evaluations 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Demographics 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Medical History 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
  Physical Examination and Vital Signsd 
X 
X 
 
X 
 
X 
 
 
 
 
 
X 
 
X 
Digital Rectal Exam 
X 
 
 
 
 
 
 
 
X 
 
 
 
 
 
ECOG Performance Status 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Cardiovascular Risk Factorsq 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
ECG 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
AEs and SAEs 
 
X 
X 
X 
X 
X 
X 
X 
X 
 
X 
X 
X 
X 
Concomitant Medications 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
X 
X 
 
X 
Prostate Cancer Treatmenth 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
X 
X 
X 
X 
Patient Reported Outcomesi 
X 
 
 
 
 
 
 
 
 
X 
 
 
X 
X 
Survival Statusf 
 
 
 
 
 
 
 
 
X 
 
X 
X 
X 
X 

P17-1 (ProVent) Protocol  
PR-2677.02, 25 January 2019  
Page 47 of 78 
Dendreon Pharmaceuticals LLC 
 
 
Proprietary and Confidential 
 
 
Item 
Screening /Baselinea 
Randomizationb 
Leukapheresis 1 
Infusion 1 (Week 0) 
Leukapheresis 2 
Infusion 2 
Leukapheresis 3 
Infusion 3 
Weeks 2, 4, 6, 10, 14, 26 
IM Visits Post 
1’st Infusione 
Every 6-Month Visit 
Post Randomizatione 
Every 12-mont Visit 
Biopsy 1 & Biopsy 2 
 
End of Active Phase Visit n 
End of Active Phase and Beginning of Follow up Phaseo 
Every 6-Month 
Follow Up Visito 
Early Withdrawal Visit p 
Visit Window 
≤30 days prior 
randomization 
 
~3 days after 
leukapheresis 1 
 
~3 days after 
leukapheresis 2 
 
~3 days after 
leukapheresis 3 
± 7 days 
± 14 days 
± 14 days 
12 to 18 & 33 to 
39 months post 
randomization 
Within 1 mo. of 
Biopsy 2 
± 1 Month 
 
Laboratory Tests  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
IHC and Gleason Score 
Xc 
 
 
 
 
 
 
 
 
 
Xj 
 
 
 
Viral Serologym 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Chemistry and Hematologyr 
X 
 
 
 
 
 
 
 
 
 
 
X 
 
X 
PSA 
Xg 
 
 
 
 
 
 
 
Xg 
 
 
 
Xt 
X 
Total Testosterone 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Immune Monitoring Sample 
Collection  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
100 mL sample l 
 
 
Xk 
 
 
 
 
Xk 
X 
 
 
 
 
 
8.5 mL sample PAXGENE RNA 
 
 
Xk 
 
 
 
 
Xk 
X 
 
 
 
 
 
2.0 mL sample PAXGENE DNA 
 
 
 
Xk 
 
 
 
 
 
 
 
 
 
 
 
 

P17-1 (ProVent) Protocol  
PR-2677.02, 25 January 2019  
Page 48 of 78 
Dendreon Pharmaceuticals LLC 
 
 
Proprietary and Confidential 
a All screening/baseline procedures must occur within 30 calendar days prior to randomization, with the exception of written informed consent and 
diagnostic biopsy 
b Randomization is the final event of Screening once eligibility of subject is confirmed by the PI. 
c Pre-study biopsy(ies) is (are) not a study procedure and the first diagnosed biopsy must have been performed ≤12 months of signing ICF.  The biopsy 
(ies) H&E and special stained slides that were used for prostate cancer diagnosis must be submitted for BICR to determine subject eligibility. 
d Complete PE including vital signs done at the clinical site at Screening (genitourinary, skin, pulmonary, cardiovascular, neurological, gastrointestinal 
& musculoskeletal) and abbreviated PE per PI’s discretion within 7 days prior to each leukapheresis and End of Active Phase Visit. Weight will be 
measured at each PE; height will be measured at Screening only. 
e The 26-week post-first-infusion visit and first 6-month visit post randomization may occur on the same visit day and only one set of immune samples 
need to be collected if the visits fall on the same day.  
f Survival status will not be obtained for subjects that are lost to follow up or withdrawn from the study. 
g PSA should be collected prior to DRE and biopsy procedures.  
h Any prostate cancer treatment (e.g., surgery, radiation, androgen deprivation therapy). 
i Patient reported outcomes/Quality of life questionnaire (IPSS, Max-PC, SF-12 and EPIC-CP) should be collected every 12 months (12-, 24-, and 36-
month visits) prior to any procedures. 
j Biopsy 1 may take place between 12 months and 18 months post randomization.  Biopsy 2 may take place between 33 months and 39 months post 
randomization. 
k Immune monitoring sample collection time points are calculated from the date of first infusion (note: not from randomization).  Samples collected on 
infusion days (i.e., Weeks 0, 2, 4) will be drawn prior to starting the sipuleucel-T infusion.  A single PAXGENE DNA sample is only collected at 
Week 0. 
l Blood draws for immune response analyses: 100mL total draw (90ml into NaHeparin Vacutainer for PBMC isolation and 10mL into no-anticoagulant 
vacutainer tubes for serum isolation). 
m Viral serology consists of hepatitis panel (HBsAg, HBsAb, HBcAb, HCV antibody(Ab), if Ab+ then HCV RNA)), HIV-1, HIV-2 antibody screen, and 
HTLV-1, HTLV-2 antibodies 
n End-of-Active Phase visit will take place within 30 days following Biopsy 2.   
o Follow-up visits will start 6 months after the End-of-Active Phase visit.  
p The early withdrawal visit must occur within 30 days of the last visit. 
q Risk factors for cardiovascular events will include diabetes mellitus, smoking history, family history, left ventricular hypertrophy, atrial fibrillation, 
hypertension, myocardial infarction and other cardiovascular disease. 
r Chemistry and/or hematology should be completed at a local lab within 7 days of leukapheresis as requested by the Apheresis center  
s First leukapheresis will be given within 60 days of randomization 
t PSA collected per standard of care, analyzed by local lab 

P17-1 (ProVent) Protocol  
PR-2677.02, 25 January 2019  
Page 49 of 78 
Dendreon Pharmaceuticals LLC 
 
 
Proprietary and Confidential 
Table 2: 
Schedule of Events for Subjects Randomized to Control 
 
 
 
Item 
Screening /Baselinea 
Randomizationb 
3-Month Visit Post 
Randomizationo 
Every 6-Month Visit 
Post Randomization 
Every 12-mont Visit 
Biopsy 1 & Biopsy 2 
 
End of Active Phase 
Visit k 
End of Active Phase and Beginning of Follow up Phase l 
Every 6-Month 
Follow Up Visitl 
Early Withdrawal 
Visit m 
Visit Window 
≤30 days prior 
randomization 
± 14 days 
± 14 days 
± 14 days 
12 to 18 & 33 
to 39 months 
post 
randomization 
Within 1 mo. 
of Biopsy 2 
± 1 Month 
 
Informed Consent 
X 
 
 
 
 
 
 
 
Prostate Biopsy  
Xc 
 
 
 
Xi 
 
 
 
Clinical Evaluations 
 
 
 
 
 
 
 
 
Demographics 
X 
 
 
 
 
 
 
 
Medical History 
X 
 
 
 
 
 
 
 
  Physical Examination and Vital Signsd 
X 
 
 
 
 
X 
 
X 
Digital Rectal Exam 
X 
 
X 
 
 
 
 
 
ECOG Performance Status 
X 
 
 
 
 
 
 
 
Cardiovascular Risk Factorsn 
X 
 
 
 
 
 
 
 
ECG 
X 
 
 
 
 
 
 
 
AEs and SAEs 
 
X 
X 
 
X 
X 
X 
X 
Concomitant Medications 
X 
X 
X 
 
X 
X 
 
X 
Prostate Cancer Treatmentg 
X 
X 
X 
 
X 
X 
X 
X 
Patient Reported Outcomesh 
X 
 
 
X 
 
 
X 
X 
Survival Statuse 
 
X 
X 
 
X 
X 
X 
X 
Laboratory Tests  
 
 
 
 
 
 
 
 
IHC and Gleason Score 
Xc 
 
 
 
Xi 
 
 
 
Viral Serologyj 
X 
 
 
 
 
 
 
 
Chemistry and Hematology 
X 
 
 
 
 
X 
 
X 
PSA 
Xf 
 
Xf 
 
 
 
Xp 
X 
Total Testosterone 
X 
 
 
 
 
 
 
 

P17-1 (ProVent) Protocol  
PR-2677.02, 25 January 2019  
Page 50 of 78 
Dendreon Pharmaceuticals LLC 
 
 
Proprietary and Confidential 
a All screening/baseline procedures must occur within 30 calendar days prior to randomization, with the exception of written informed 
consent and diagnostic biopsy 
b Randomization is the final event of Screening once eligibility of subject is confirmed by the PI. 
c Pre-study biopsy(ies) is (are) not a study procedure and must have been performed ≤12 months of signing ICF.  The biopsy (ies) 
H&Eand special stained slides that were used for prostate cancer diagnosis must be submitted for BICR to determine subject 
eligibility. 
d Complete PE including vital signs done at the clinical site at Screening (genitourinary, skin, pulmonary, cardiovascular, neurological, 
gastrointestinal & musculoskeletal) and abbreviated PE per PI’s discretion at the End of Active Phase Visit. Weight will be measured 
at each PE; height will be measured at Screening only. 
e  Survival status will not be obtained for subjects that are lost to follow up or withdrawn from the study. 
f PSA should be collected prior to DRE and biopsy procedures 
g Any prostate cancer treatment (e.g., surgery, radiation, androgen deprivation therapy) 
h Patient reported outcomes/Quality of life questionnaire (Max-PC, SF-12 EPIC-CP, and IPSS) should be collected every 12 months 
(12-, 24-, and 36-month visits) prior to any procedures on the specified visits. 
i Biopsy 1 may take place between 12 months and 18 months post randomization.  Biopsy 2 may take place between 33 months and 39 
months post randomization. 
j Viral serology consists of hepatitis panel (HBsAg, HBsAb, HBcAb, HCV antibody(Ab), if Ab+ then HCV RNA)), HIV-1, HIV-2 
antibody screen, and HTLV-1, HTLV-2 antibodies 
k End-of-Active Phase visit will take place within 30 days following Biopsy 2. 
l Follow-up visits will start 6 months after the End-of-Active Phase visit. 
m  The early withdrawal visit must occur within 30 days of the last visit. 
n  Risk factors for cardiovascular events will include diabetes mellitus, smoking history, family history, left ventricular hypertrophy, 
atrial fibrillation, hypertension, myocardial infarction and other cardiovascular disease. 
o 3-month visit post randomization may be conducted in the office or via phone.  
p PSA collected per standard of care, analyzed by local lab 
 
 

P17-1 (ProVent) Protocol  
PR-2677.02, 25 January 2019  
Page 51 of 78 
Dendreon Pharmaceuticals LLC 
 
 
Proprietary and Confidential 
8.2 
Informed Consent 
Informed consent will be obtained as described in Section1.4.   
8.3 
Screening 
All subjects must sign an ICF prior to the conduct of any study-related procedures.  A screening 
number will be assigned for each subject.  Screening procedures will be performed up to 30 days 
prior to randomization to allow sufficient time for blood chemistries and submission of all 
original stained pathology slides along with local pathology report for BICR to determine ISUP 
Grade Group for inclusion criteria and randomization.  All subject information should be 
redacted from the local pathology reports and slides.  Local pathology reports and slides will be 
identified only by subject screening number.  If a subject has more than one biopsy following 
their prostate cancer diagnosis, slides from each subsequent biopsy will be sent for BICR.  The 
central pathologist’s report will determine whether the subject meets the prostate cancer 
eligibility criteria (Section 6.0).  All slides will be returned to the clinical trial site.  In the case 
of multiple biopsies, the biopsy with the highest ISUP Grade Group will be used as baseline. 
See the complete list of inclusion and exclusion criteria (Section 6.0) and the Schedule of Events 
(Table 1 and Table 2) for study details. 
Subjects who do not meet all inclusion criteria and/or who meet one or more exclusion criteria 
may be rescreened.  Rescreening is at the discretion of the investigator, but requires sponsor 
approval in writing.  Subjects who are to be rescreened must sign a new ICF prior to rescreening.  
Rescreened subjects who had their initial screening performed within 30 days of randomization 
may use the initial screening laboratory results.  Rescreened subjects may use the initial ISUP 
Grade Group determined by BICR if no additional biopsy has been administered.  Rescreening 
and subsequent randomization activities must be conducted in accordance with all protocol-
defined windows and timelines. 
Subjects who do not meet all eligibility criteria will be considered screen failures and will 
undergo no further study procedures.  The reason(s) for each screen failure will be recorded in 
the subject’s medical record and on the eCRF. 
8.4 
Randomization 
Eligible subjects will be randomized to the sipuleucel-T arm or control arms in a 2:1 ratio based 
on a predetermined, computer-generated randomization schedule.  The randomization will be 
balanced by using block randomization.   
Stratification will be based on: 
• ISUP Grade Group 1 or 2 
• Number biopsies 1 or >1 (≤12 months of Screening) 

P17-1 (ProVent) Protocol  
PR-2677.02, 25 January 2019  
Page 52 of 78 
Dendreon Pharmaceuticals LLC 
 
 
Proprietary and Confidential 
Randomization will take place across all clinical trial sites using an Interactive Response 
Technology (IRT).  The IRT will assign a unique code, which will dictate the assignment to 
either sipuleucel-T arm or control arm.  The requestor must use his or her own user identification 
and personal identification number when contacting the IRT, and will then give the relevant 
subject details to uniquely identify the subject. 
8.5 
Demographics and Medical History  
Demographic information, including birth date, race, and ethnicity will be recorded.   
Medical history will include date of prostate cancer diagnosis, ISUP Grade Group and prostate 
biopsy history.  Significant historic (within the previous 5 years) and current medical conditions 
or illnesses, allergies to medications, and surgical interventions occurring prior to informed 
consent will be recorded.  Medical history will include the subject’s serum PSA values and 
vaccinations in the 2 years prior to signing informed consent. 
8.6 
Clinical Assessments 
8.6.1 
Physical Examination and Vital Signs 
PEs must be conducted by an appropriately qualified investigator listed on Form FDA 1572.   
Complete PEs will be performed at Screening and include a review of body systems 
(genitourinary, 
skin, 
pulmonary, 
cardiovascular, 
neurological, 
gastrointestinal 
and 
musculoskeletal.  Review of additional body systems will be at the discretion of the investigator.   
For the sipuleucel-T arm abbreviated PEs will be performed on the day of leukapheresis or 
within 7 days prior to leukapheresis.  For both sipuleucel-T and control arms abbreviated PEs 
will be performed at the End of Active Phase Visit or at the Early Withdrawal Visit.  Weight 
will be measured at each PE; height will be measured at Screening only. 
Vital signs (respiration rate, temperature, heart rate, and blood pressure) will be measured at the 
time points noted in Schedule of Events (Table 1 or Table 2).  
8.6.2 
Digital Rectal Exam  
DRE will be performed at screening and each 6-month visit in the Active Phase and should be 
performed after blood draw for PSA. 
8.6.3 
Electrocardiograms 
A 12-lead ECG will be recorded at Screening.  Abnormalities noted at Screening will be 
included in the medical history. 

P17-1 (ProVent) Protocol  
PR-2677.02, 25 January 2019  
Page 53 of 78 
Dendreon Pharmaceuticals LLC 
 
 
Proprietary and Confidential 
8.6.4 
Eastern Cooperative Oncology Group Performance Status 
ECOG performance status (Appendix 1) will be assessed at Screening.  The assessment must 
be conducted by an appropriately qualified investigator listed on the Form FDA 1572 and noted 
on the delegation log. 
8.6.5 
Cardiovascular Risk Factors 
Risk factors for cardiovascular events will be recorded at Screening and will include diabetes 
mellitus, smoking history, family history, left ventricular hypertrophy, atrial fibrillation, 
hypertension, myocardial infraction, and other cardiovascular disease. 
8.6.6 
Multiparametric Magnetic Resonance Imaging (mpMRI) Imaging Study 
When available, existing mpMRI prostate imaging studies performed prior to randomization 
and as part of the original prostate cancer diagnosis or subsequent prostate biopsies will be 
documented in the eCRF.  Comparative mpMRI prostate imaging studies performed on study 
will be captured in the eCRF. 
8.7 
Patient Reported Outcomes 
PRO data will be collected to evaluate health-related quality of life for men on AS and the 
impact of any subsequent therapy for prostate cancer.  Four instruments SF-12 (Appendix 2), 
MAX-PC (Appendix 3), EPIC-CP (Appendix 4), and the IPSS (Appendix 5) will be 
administered at Screening, annually during the Active Phase at 12-, 24-, and 36-month visits, 
and every 6 months in the Follow up Phase or Early Withdrawal Visit.  SF-12 evaluates the 
general quality of life, MAX-PC evaluates a subject’s anxiety related to prostate cancer 
diagnosis, EPIC-CP measures quality of life issues in patients with prostate cancer, and the IPSS 
evaluates patient’s urinary voiding symptoms.  PROs should be administered prior to any 
procedures or measurements.  The clinical site staff must review the completed PRO’s with the 
subject prior to leaving the facility to ensure that PROs have been completed correctly. 
8.8 
Adverse Events and Serious Adverse Events 
AE and SAE assessments will be performed in conjunction with visits as indicated in Schedule 
of Events (Table 1 and Table 2) and as needed throughout the study.  All AEs and SAEs will be 
recorded in the subject’s medical record and on the eCRF.  In addition all SAEs will be reported 
on the sponsor’s SAE report form. 
See Section 9.1 for information regarding AE and Section 9.2 for information regarding SAEs. 
8.9 
Concomitant Medications and Therapies 
All concomitant medications that are ongoing at informed consent or administered during the 
Active Phase will be recorded at each scheduled and unscheduled study visit in the subject’s 
medical record and eCRF.  See Section 6.7 and Section 6.8 for restricted therapies.  Only 

P17-1 (ProVent) Protocol  
PR-2677.02, 25 January 2019  
Page 54 of 78 
Dendreon Pharmaceuticals LLC 
 
 
Proprietary and Confidential 
prostate cancer treatments (e.g., surgery, radiation, androgen deprivation therapy) administered 
during the Follow-up Phase visits will be recorded in the subject’s medical record and eCRF. 
8.10 
Clinical Laboratory Tests  
Clinical laboratory test samples will be collected at the time points noted in the Schedule of 
Events (Table 1 and Table 2).  Samples will be tested for the parameters presented in Table 3.  
All clinical laboratory tests will be performed by a central laboratory, and the results will be 
reported to the clinical trial site. 
Table 3: 
Laboratory Tests 
HEMATOLOGY 
CLINICAL CHEMISTRY 
Hemoglobin (HgB) 
Total bilirubin 
Hematocrit 
Alkaline phosphatase 
Red blood cell count (RBC) 
Lactic Dehydrogenase (LDH) 
White blood cell count (WBC) 
Alanine aminotransferase (ALT/SGPT) 
Absolute neutrophil count (ANC) 
Aspartate aminotransferase (AST/SGOT) 
Lymphocyte count 
Blood urea nitrogen (BUN) 
Monocyte count 
Serum creatinine 
Eosinophil count 
Calcium  
Basophil count 
Magnesium  
Platelet count 
Glucose  
OTHER BLOOD TESTS 
Albumin 
Total testosterone 
Total Protein 
Prostate-specific antigen (PSA) 
Sodium  
VIRAL SEROLOGY 
Potassium  
Human Immunodeficiency Virus (HIV-1 and HIV-2) 
Bicarbonate  
Hepatitis panel (HBsAg, HBsAb, HBcAb, HCV 
antibody(Ab), if Ab+ then HCV RNA)) 
Chloride  
Human T-Lymphotropic Virus (HTLV-1, HTLV-2) 
Phosphorus 
 
8.11 
Histopathology Assessment 
During the Active Phase, subjects will have all H&E and special stained slides and local 
pathology reports from Biopsy 1 and Biopsy 2, as well as any unscheduled biopsies, assessed 
for histopathologic grading by BICR.  Slides from each biopsy will be considered as a group to 
determine the ISUP Grade Group as opposed to any single slide.  All subject information should 
be redacted from the local pathology reports and slides.  Local pathology reports and slides will 
be identified only by study subject number.  All slides will be returned to the clinical trial site. 
Subjects on the Active Phase undergoing a radical prostatectomy will submit H&E and special 
stained slides from prostate slices for BICR as described above.  These will be compared to the 
ISUP Grade Group determined from previous biopsy.  FFPE tissue blocks from the radical 
prostatectomy as requested by central pathology will be submitted for IHC.  

P17-1 (ProVent) Protocol  
PR-2677.02, 25 January 2019  
Page 55 of 78 
Dendreon Pharmaceuticals LLC 
 
 
Proprietary and Confidential 
Subjects with an ISUP Grade Group upgrade and who remain on AS (i.e., do not undergo 
prostate cancer therapy) will remain in the Active Phase and continue per the Schedule of Events 
(Table 1 and Table 2).  
8.12 
Immunohistochemistry Evaluations  
Post randomization, specific FFPE tissue blocks from biopsies or surgery will be requested by 
central pathology from their BICR that represents areas of cancer and benign prostate tissue 
identified on H&E and special stained slides.  All subject information should be redacted from 
the FFPE blocks, and FFPE blocks should be identified only by study subject number.  These 
blocks will be freshly cut by the central pathology for IHC to assess infiltration and 
classification of lymphocytes (e.g., CD3, CD4, CD8, FoxP3, CD56, Ki67, CD279, MECA-79) 
to prostate cancer tissue.  The geographic distribution of T cell phenotypes will be described 
relative to the tumor (central, peripheral, adjacent, or benign tissue localization).  All FFPE 
blocks will be returned to the clinical trial site. 
8.13 
Sipuleucel-T Immune Monitoring Assessments 
Blood samples for immune monitoring will be collected at the time points noted in the Schedule 
of Events (Table 1) for subjects randomized to the sipuleucel-T arm. 
Immune monitoring assessments will include proliferation assays to evaluate PA2024- and 
PAP-specific T cell responses, IFN-γ ELISPOT assays to assess the number of PA2024- and 
PAP-specific T cells, and enzyme-linked immunosorbent assay (ELISA) to assess humoral 
response to PA2024 and PAP.  Fluorescent immunoassays will be used to determine the number 
and activation status of subtypes of T cells, B cells, and NK cells, and the levels and types of 
cytokines. 
8.13.1 
Sipuleucel-T Product Parameters 
Prior to infusion, samples from pre and post-culture sipuleucel-T are used to assess product 
parameters as part of the sipuleucel-T manufacturing process.  Sipuleucel-T product parameters 
include total nucleated cell (TNC) count, APC count, and APC activation. 
8.13.2 
Sipuleucel-T Product Characterization 
Samples of final product will be used to characterize sipuleucel-T utilizing flow cytometry, 
protein array, spectral analyses, ELISA, and Luminex assays to assess the immune response.  
Tests may include assessment of the number and activation status of subtypes of T cells, B cells, 
and NK cells, and the levels and types of cytokines produced during the manufacture of 
sipuleucel-T. 
8.13.3 
Additional Optional Research (AOR) 
At the time of informed consent, subjects will be given the opportunity to consent to participate 
in AOR.  Subjects who consent to AOR agree to allow sponsor or designee to retain their 

P17-1 (ProVent) Protocol  
PR-2677.02, 25 January 2019  
Page 56 of 78 
Dendreon Pharmaceuticals LLC 
 
 
Proprietary and Confidential 
samples (obtained from blood collection for immune monitoring, PAXGENE RNA and DNA, 
and sipuleucel-T product parameters and characterization, during manufacture) indefinitely and 
to use them for other testing.  For subjects who consent to AOR, no additional blood collections 
will be required beyond those already being collected as part of the study. 
AOR may include genetic testing, and retained samples may be sent to outside laboratories for 
testing. 
Samples retained for AOR will be used for research only, will not be sold, and will not be 
identified using subject names or other personal identifiers. 
FFPE tissue blocks from biopsies used for screening and on study biopsies or radical 
prostatectomy may be requested by the sponsor for genomic analysis of prostate cancer 
progression risk. 
8.13.4 
Sample Retention 
Blood or serum samples obtained for clinical laboratory testing from all subjects will be retained 
by the central laboratory for up to 7 days and will then be destroyed. 
Blood or serum samples obtained for immune monitoring, or manufacturing process samples 
for sipuleucel-T product parameters and characterization will be retained for up to 5 years 
following sponsor’s completion of the trial and will then be destroyed.  Subjects who consent 
to AOR agree for the sponsor to retain the samples indefinitely. 
Samples obtained or used for immune monitoring and sipuleucel-T product parameters and 
characterization from subjects who provide consent for AOR may be retained indefinitely. 
FFPE tissue blocks obtained for IHC and genomic analysis will be returned to the sites.  
9.0 
SAFETY 
Timely, accurate, and complete reporting and analysis of safety information from clinical 
studies are crucial for the protection of subjects, investigators, and the sponsor, and are 
mandated by regulatory agencies worldwide.   Safety reporting for this trial will be conducted 
in accordance with 21 CFR 312.32 as amended by the Final Rule published September 29, 2010 
and detailed in the Guidance for Industry and Investigators: Safety Reporting Requirements for 
INDs and BA/BE Studies (December 2012).  Sponsor will be the final arbiter, should a 
difference of opinion exist regarding the nature, seriousness, severity, or relatedness of AEs. 
9.1 
Adverse Events 
9.1.1 
Definition of Adverse Event 
An AE is defined as any untoward medical occurrence in a subject while participating in a study 
that does not necessarily have a causal relationship with sipuleucel-T.  An AE can, therefore, 
be any unfavorable and unintended sign (e.g., abnormal laboratory finding), symptom, or 

P17-1 (ProVent) Protocol  
PR-2677.02, 25 January 2019  
Page 57 of 78 
Dendreon Pharmaceuticals LLC 
 
 
Proprietary and Confidential 
disease temporally associated with sipuleucel-T, whether or not considered related to 
sipuleucel-T.  AEs include exacerbation of a pre-existing illness, an increase in frequency or 
intensity of a pre-existing episodic event or condition, a condition detected or diagnosed after 
product administration (even though it may have been present prior to the start of the study) or 
a continuous persistent disease or symptoms present at Screening that worsen following the start 
of the study. 
9.1.2 
Categories for Ranking Severity of Adverse Events 
The most current version of the National Cancer Institute Common Terminology Criteria for 
Adverse Events (NCI CTCAE) will be used to score AE severity by grades.  In general, the 
following severity definitions apply: 
Mild (grade 1): 
The AE results in mild, easily tolerated symptoms, or is 
asymptomatic with clinical or diagnostic observations 
only.  Intervention is not usually indicated. 
Moderate (grade 2): 
The AE produces moderate symptoms with discomfort 
sufficient to interfere with some aspect of the subject’s 
normal daily activity.  Minimal, local, or noninvasive 
intervention is required. 
Severe (grade 3): 
The AE is medically significant but not immediately life 
threatening, results in discomfort or disability which is 
incapacitating and prevents most normal daily activities, 
clearly damaging to the health, requiring hospitalization, 
prolongation of existing hospitalization or complicated 
treatment. 
Life-threatening (grade 4): 
The AE could reasonably be expected to result in death 
unless immediate medical intervention is undertaken. 
Fatal (grade 5): 
The AE results in death. 
 
9.1.3 
Relationship of Adverse Events to Sipuleucel-T  
The following categories will be used to determine relationship of AEs to sipuleucel-T: 

P17-1 (ProVent) Protocol  
PR-2677.02, 25 January 2019  
Page 58 of 78 
Dendreon Pharmaceuticals LLC 
 
 
Proprietary and Confidential 
None: 
The AE is clearly related to other factors, such as the subject’s 
clinical state, environmental factors, or other modes of therapy or 
concomitant medications administered to the subject. 
Possible: 
The AE follows a reasonable temporal sequence from 
administration of sipuleucel-T, but could readily have been 
produced by the subject’s clinical state, environmental factors, or 
other modes of therapy or concomitant medications administered 
to the subject. 
Probable: 
The AE follows a reasonable temporal sequence from 
administration of sipuleucel-T and could not readily have been 
produced by the subject’s clinical state, environmental factors, or 
other modes of therapy or concomitant medications administered 
to the subject. 
 
9.1.4 
Recording and Reporting Adverse Events 
All AEs and SAEs in the sipuleucel-T arm and control arm will be collected from randomization 
through the subject’s last study visit.  AEs and SAEs will be reported and recorded in the 
subject’s medical record and entered on their eCRF. 
All AEs and SAEs reported in either the sipuleucel-T or control arms will be followed by the 
investigator until resolution, return to baseline, or the investigator determines that no further 
improvement is expected until study completion.  The start and stop dates, description, 
seriousness, toxicity, relationship to study treatment, and outcome will be recorded. 
9.2 
Serious Adverse Events 
9.2.1 
Definition of Serious Adverse Event 
An SAE is defined as any adverse drug experience occurring at any dose that results in any of 
the following outcomes: death, a life-threatening adverse drug experience, subject 
hospitalization or prolongation of an existing hospitalization, a persistent or significant 
disability/incapacity, or a congenital anomaly/birth defect.  An important medical event that 
may not result in death, be life-threatening, or require hospitalization may be considered an SAE 
when, based upon appropriate medical judgment, it may jeopardize the subject and may require 
medical or surgical intervention to prevent one of the outcomes listed in this definition.  
Examples of such medical events include allergic bronchospasm requiring intensive treatment 
in an emergency room or at home, blood dyscrasias or convulsions that do not result in subject 
hospitalization, or the development of drug dependency or drug abuse. 

P17-1 (ProVent) Protocol  
PR-2677.02, 25 January 2019  
Page 59 of 78 
Dendreon Pharmaceuticals LLC 
 
 
Proprietary and Confidential 
9.2.2 
Recording and Reporting of Serious Adverse Events 
All SAEs in the sipuleucel-T arm and control arm from randomization through the subject’s last 
study visit will be reported on sponsor’s SAE Report Form. 
All SAEs reported in both arms will be followed by the investigator until resolution, return to 
baseline, or the investigator determines that no further improvement is expected until study 
completion. 
SAEs must be reported to sponsor or designee within 24 hours of the clinical trial site’s 
awareness of the events by completing the sponsor’s SAE Report Form if they meet the criteria 
described in Section 9.2.1.  If access to the SAE Report Form is unavailable for any reason, the 
SAE information must be reported to sponsor or designee within 24 hours by email or facsimile 
and a completed written report using sponsor’s SAE Report form within 3 business days to:   
Dendreon Pharmaceuticals LLC 
Attention: 
DrugSafety@dendreon.com 
Significant new information regarding each SAE must be reported to sponsor or designee by 
recording the information on the SAE Report Form within 24 hours of the clinical trial site’s 
awareness of the new information and reported as noted above. 
9.2.3 
Death Reports 
 
Deaths that occur during the study will be reported as SAEs and will be recorded in the subject’s 
medical record, sponsor’s SAE Report Form and on the eCRF. 
9.2.4 
Expedited Reporting Requirements 
Sponsor will notify the appropriate regulatory authorities and all participating Principal 
Investigators of any AE that is serious, unexpected and considered to be at least possibly related 
to sipuleucel-T.  Such notification will be provided within 15 calendar days after Sponsor or 
designee’s initial receipt of the information.  If such an event is fatal or life-threatening, the 
appropriate regulatory authorities will be notified no later than 7 calendar days after Sponsor or 
designee’s initial receipt of the information. 
Serious adverse events that are expected, such as disease progression, will not be reported by 
sponsor on an expedited basis.  See the sipuleucel-T Investigator’s Brochure for additional 
information regarding expected SAEs. 
The Principal Investigator is responsible for notifying the relevant IRB of any SAE that occurs 
in a subject participating at their clinical trial site or any IND Safety Reports issued by sponsor, 
unless otherwise instructed by relevant IRB policy. 

P17-1 (ProVent) Protocol  
PR-2677.02, 25 January 2019  
Page 60 of 78 
Dendreon Pharmaceuticals LLC 
 
 
Proprietary and Confidential 
9.3 
Laboratory Test Result Abnormalities 
The following laboratory abnormalities will be considered AEs and recorded in the subject’s 
medical record and on the eCRF: 
• Any clinically significant result that is not part of another reported clinical diagnosis 
• Any result that meets the definition of an SAE 
• Any result leading to discontinuation or interruption of sipuleucel-T 
• Any result that requires therapeutic intervention or a change in subject management 
Laboratory abnormalities that do not meet the above conditions will not be recorded on the 
eCRF. 
10.0 
STATISTICAL CONSIDERATIONS 
The Phase 3, open-label study is designed to assess the effects of sipuleucel-T in subjects on 
AS.  Subjects will be randomized 2:1 to either a sipuleucel-T arm (investigational arm) or a 
control arm, stratified by the ISUP Grade Group 1 or 2 and the number of biopsies showing the 
presence of disease prior to registration.  Data will be analyzed by arm under the intent-to-treat 
(ITT) principle.  Generally statistical tests will be performed at the 2-sided 0.05 significance 
level unless otherwise noted.  
The phrases ‘statistical analysis’ or ‘analysis’ will be used to mean inferential analysis (such as 
performing tests of significance, reporting p-values and confidence intervals).  When no 
inferential analysis will be performed, the phrases ‘descriptive analysis’ or ‘descriptive 
statistics’ will be used (for instance, producing summary tables of means, standard deviations, 
percentages of responders).   
Statistical analysis will be done by the sponsor or under the authority of the sponsor.  A general 
description of the statistical methods to be used to analyze the efficacy and safety data is 
outlined below.  Details will be provided in the Statistical Analysis Plan (SAP). 
10.1 
Sample Size Considerations 
The primary endpoint will analyze approximately 450 subjects randomized (2:1 sipuleucel-T 
versus control arm), and for each subject, is dichotomous with success defined as having been 
observed to be free of histopathologic upgrade after 36 months of follow-up.  Based on data 
available, it is estimated that the proportion of histopathologic upgrading by 36 months 
following randomization for control arm subjects will be approximately 0.30.  While there is no 
prior information on treatment response to sipuleucel-T in early stage disease available, a 
meaningful hypothesized reduction in this proportion is a reduction by 0.14, giving a projected 
outcome proportion of upgrading in the sipuleucel-T arm of 0.16.  The null hypothesis of both 
arms having a proportion of 0.70 (= 1- 0.3) being free from upgrading at 36 months versus the 

P17-1 (ProVent) Protocol  
PR-2677.02, 25 January 2019  
Page 61 of 78 
Dendreon Pharmaceuticals LLC 
 
 
Proprietary and Confidential 
specific alternative hypothesis of a sipuleucel-T arm outcome of 0.84 (= 1- 0.16).  The odds 
ratio associated with the specific alternative hypothesis is 2.25 (sipuleucel-T arm odds over 
control arm odds).  Based on an overall 1-sided alpha of 0.025 approximately 300 subjects in 
the sipuleucel-T arm and 150 subjects in the control arm will provide 90% power to demonstrate 
the superiority of sipuleucel-T to control. 
10.2 
Analysis Populations 
The Safety Analysis Population is defined as all randomized patients; the Sipuleucel-T safety 
population must have begun the treatment process. 
The intent-to-treat (ITT) population is defined as all randomized subjects. 
The Per Protocol (PP) population is defined as the subset of patients in the ITT population who 
have completed all assessment per the protocol.   
10.3 
Efficacy Analysis 
The phrases ‘statistical analysis’ or ‘analysis’ will be used to mean inferential analysis (such as 
performing tests of significance, reporting p-values and confidence intervals).  When no 
inferential analysis will be performed, the phrases ‘descriptive analysis’ or ‘descriptive 
statistics’ will be used (for instance, producing summary tables of means, standard deviations, 
percentages of responders).  All efficacy analyses will be conducted on the ITT population and 
the per protocol population.  
Unless otherwise specified, the statistical tests are based on the superiority hypothesis using a 
one-sided p-value of 0.025 (equivalent to two-sided 0.05 with a result in the hypothesized 
direction).  The final analysis will be performed after all subjects have completed the 36 month 
biopsy, or have histopathologic upgrade or have withdrawn from the study.   
10.4 
Interim Analysis 
No interim analysis is proposed. 
10.5 
Analysis of Study Endpoints 
10.5.1 
Primary Endpoint 
The primary endpoint is the proportion of subjects without a histopathologic upgrade over the 
36-months following randomization and will be summarized by study arm.  The primary 
endpoint for each subject is dichotomous with success defined as having been observed to be 
free of histopathologic upgrade at Biopsy 2 33 to 39 months after randomization.  
Histopathologic upgrading occurs when a subject with ISUP Grade Group 1 prostate cancer, at 
randomization, is upgraded to Grade Group 2 or higher, or a subject with ISUP Grade Group 2 
prostate cancer, at randomization, is upgraded to Grade 3 or higher as determined by BICR, at 
any post-randomization biopsy.  Histopathologic status is determined by biopsy and will be 
assessed at the scheduled biopsy or at any biopsy that is taken during radical-prostatectomy or 

P17-1 (ProVent) Protocol  
PR-2677.02, 25 January 2019  
Page 62 of 78 
Dendreon Pharmaceuticals LLC 
 
 
Proprietary and Confidential 
other time-point.  Subjects upgrading before 36 months, or those found as upstaged at Biopsy 
2, or those not observed at 36 months (i.e., do not complete Biopsy 2 prior to 39 months post 
randomization) will be regarded as failures in the primary analysis.  
The primary analysis null hypothesis, H0: Ω ≤ 1, versus the alternative hypothesis, HA: Ω > 1; 
where Ω is the odds of success in the sipuleucel-T arm over the odds of success in the control 
arm.  The Cochran-Mantel-Haenszel (CMH) test, stratified by ISUP Grade Group 1 or 2 and 
the number of biopsies showing the presence of disease prior to registration will be used to 
estimate the odds ratio, and will be computed using exact methods based on Monte Carlo 
computations due to the potential for small frequencies. 
10.5.2 
Secondary Endpoints 
The subsequent prostate cancer treatment, if any, for each subject will be determined.  The 
category of subsequent prostate cancer treatment will be identified (e.g., surgery, radiation, 
androgen deprivation therapy).  Subjects initiating alternative intervention will be regarded as 
sipuleucel-T treatment failures.  These data will be summarized descriptively and compared 
between study arms using the Cochran-Mantel-Haenszel test. 
Quality of life data will be summarized descriptively and compared between study treatment 
arms and in the aggregate within the efficacy population.  
Safety data will be summarized descriptively by study treatment arms and in the aggregate 
within the safety population. 
10.5.3 
Exploratory Endpoints 
Immune response will be assessed at each specified time-point.  Immune response variables will 
be evaluated to determine if there is a correlation between the measures of immune response 
and upgrade or other changes to the ISUP group grade of the subject’s prostate cancer.   
Subjects undergoing a radical prostatectomy will have the biopsy sample evaluated for 
histological status of the prostate cancer.  Histopathologic change will be defined as any change 
in ISUP grade at baseline to an upgrade, no change in, or down-grade to a their ISUP baseline 
grade group designation, or to a status indicating no prostate cancer disease identified.  These 
data will be summarized descriptively and compared between study arms.   
Biopsy results will be assessed to determine the rate of negative biopsy results.  This data will 
be summarized descriptively and compared between study arms. 
PSA velocity will be calculated as the slope of the simple linear regression of the natural log of 
PSA versus time. 
10.5.4 
Biomarker Analysis 
The association of biomarkers with clinical response endpoints or survival may be assessed 
using appropriate statistical methods (e.g., analysis of variance [ANOVA], categorical or 

P17-1 (ProVent) Protocol  
PR-2677.02, 25 January 2019  
Page 63 of 78 
Dendreon Pharmaceuticals LLC 
 
 
Proprietary and Confidential 
survival models) depending on the endpoints.  Other clinical covariates (such as baseline tumor 
characteristics and subject demographics) may also be included in the model.  Association of 
biomarkers with clinical response or relevant time-to-event endpoints will also be explored in 
the overall population.  Results of these exploratory analyses will be presented in separate 
technical reports.  
10.5.5 
Safety 
The safety parameters to be analyzed are the incidence, intensity, and type of AEs, vital signs, 
clinical laboratory results, and limited physical examinations (abnormalities will be recorded as 
AEs (Section 9.3).  Analysis of the safety parameters will be conducted on the safety population. 
10.5.5.1 
Adverse Events 
AEs will be summarized and listed using the Medical Dictionary for Regulatory Activities 
(MedDRA version 18.0 or later) by preferred term within each body system.  Tables to be 
produced will include the number and incidence of the following:  
• Incidence within system organ class 
• Incidence by decreasing frequency 
• Incidence by NCI CTCAE (most current version) severity grade, by decreasing 
frequency 
• Incidence within 1 day of infusion  
• Incidence of SAEs 
• Incidence of AEs that resulted in premature discontinuation of study  
AEs that occur multiple times for a subject will be counted only once per subject in incidence 
summary tables.  In tables that enumerate AEs by severity, only the greatest severity for an AE 
occurring multiple times for a subject will be counted. 
10.5.5.2 
Clinical Laboratory Data 
Clinical laboratory test results will be summarized by type of laboratory test.  For continuous 
measurements, descriptive statistics will be calculated at baseline and for observed values and 
changes from baseline at each scheduled time point.  The number and percentage of subjects 
with abnormal values will be summarized.  The number and percentage of subjects with 
parameters with NCI-CTCAE toxicity Grade of ≥3 will be summarized.  Shift in toxicity grade 
from baseline to the worst grade experienced by the subject during the study will be provided. 
10.5.5.3 
Other Clinical Assessments 
Descriptive statistics of blood pressure (systolic and diastolic) values and changes from baseline 
will be summarized at each scheduled time point.  Descriptive statistics of other vital signs 

P17-1 (ProVent) Protocol  
PR-2677.02, 25 January 2019  
Page 64 of 78 
Dendreon Pharmaceuticals LLC 
 
 
Proprietary and Confidential 
(body temperature, heart rate, respiratory rate) at baseline will also be summarized.  The number 
and percentage of subjects with values beyond clinically important limits will be summarized. 
Abnormal findings in physical examination will be recorded and summarized as AEs.  Weight 
will be summarized and DRE results will be provided in a listing.  
10.5.6 
Other 
10.5.6.1 
Demographics and Baseline Characteristics 
Demographic information and baseline disease characteristics will be summarized descriptively 
for the primary analysis population and the treated and safety populations.  
10.5.6.2 
Subject Disposition 
The following subject disposition information will be summarized: 
• Number of subjects in the primary analysis population 
• Number of subjects in the treated population 
• Number of subjects in the safety population 
• Number of subjects who prematurely discontinued the study and the associated reasons 
for early termination  
10.5.6.3 
Sipuleucel-T Administration 
The following leukapheresis and infusion information will be summarized for all registered 
subjects: 
• Number of subjects who received a total of 0, 1, 2, or 3 infusions 
• Reason(s) for not completing 3 infusions 
• Number of subjects who receive a total of 0, 1, 2, 3 4, or 5 or more leukapheresis 
• Number of subjects who receive a total of 3 leukapheresis and 3 infusions 
10.5.6.4 
Sipuleucel-T Product Parameters 
Sipuleucel-T product parameters (TNC count, APC count, and APC activation) will be 
summarized by Infusion 1, 2, 3, cumulative through Infusion 2, and cumulative through Infusion 
3.  

P17-1 (ProVent) Protocol  
PR-2677.02, 25 January 2019  
Page 65 of 78 
Dendreon Pharmaceuticals LLC 
 
 
Proprietary and Confidential 
10.5.6.5 
Concomitant Medications and Therapies 
Concomitant medications will be coded using the World Health Organization dictionary 
(WHODRUG).   
All concomitant medications will be summarized by anatomical-therapeutic-chemical 
classification (ATC) text and preferred term.  Separate summaries will be provided for 
medications ongoing at the time of informed consent and for medications started after informed 
consent.   
11.0 
STUDY MANAGEMENT 
11.1 
Study Materials 
Sponsor or designee will provide an approved protocol and any required amendments or 
administrative letters, the current Investigator’s Brochure, and the eCRF.  Dendreon or designee 
will also provide leukapheresis services at a Dendreon-qualified leukapheresis center and all 
applicable study-specific training materials and reference binders.  Sponsor or designee will 
additionally provide materials needed for the collection and shipment of laboratory samples, 
including samples for immune monitoring. 
The clinical trial site will provide all other supplies required to conduct the study at the clinical 
trial site. 
11.2 
Study Documentation 
The Principal Investigator and clinical trial site personnel are responsible for maintaining a 
comprehensive and centralized filing system containing all study-related documentation.  These 
files must be suitable for inspection by Dendreon or designee, IRBs, FDA, or other regulatory 
authorities at any time, and should consist of the following: 
• Copies of completed eCRFs 
• Subject files, containing supporting source documentation from the subject’s medical 
record, including clinical laboratory data, pathology reports, and the original signed ICF 
(including any updated ICFs requiring re-consenting) 
• Essential documents, as defined in ICH E6 Guideline for GCP 
• Drug accountability files, containing a complete account of the receipt and disposition 
of all sipuleucel-T infusions 
The Principal Investigator shall retain records for a period of 2 years following the date a 
marketing application is approved for the drug for the indication for which it is being 
investigated; or, if no application is to be filed or the application is not approved for such 
indication, until 2 years after the investigation is discontinued and FDA is notified. 

P17-1 (ProVent) Protocol  
PR-2677.02, 25 January 2019  
Page 66 of 78 
Dendreon Pharmaceuticals LLC 
 
 
Proprietary and Confidential 
11.3 
Protocol Compliance 
To ensure accurate interpretation and implementation of the study, the protocol will be carefully 
reviewed by the Principal Investigator and the clinical trial site personnel prior to study 
initiation. 
Any non-adherence to the protocol, FDA regulations, or GCP will be considered a protocol 
deviation, and will be discussed during a monitoring visit and documented via a visit follow-up 
letter.  The Principal Investigator will be responsible for reporting protocol deviations to the 
IRB per the IRB’s reporting requirements. 
A protocol exception is a specific type of protocol deviation wherein a subject does not meet 
eligibility requirements for the study, but a waiver allowing the subject to enter the study is 
prospectively granted by sponsor.  Protocol exceptions are rarely considered, and are granted 
only when a subject’s participation will not confound analysis or interpretation of safety data. 
11.4 
Monitoring 
A sponsor monitor or designee will visit the clinical trial site periodically to monitor adherence 
to the protocol, adherence to applicable FDA regulations, adherence to ICH E6 Guideline for 
GCP, and the maintenance of adequate and accurate records.  Electronic case report forms will 
be reviewed to ensure that key safety and efficacy data are reported as specified by the protocol.  
The sponsor monitor or designee must be permitted to access subjects’ complete medical 
records, laboratory data, and other source documentation as needed to appropriately monitor the 
trial. 
In addition to monitoring visits to the site, site management contacts (via phone/email) will be 
scheduled with the site to review study-related topics, such as, enrollment status, study staff 
training/turnover, safety reporting, data entry and query resolution, regulatory documentation 
status, study materials/expiration status, and principal investigator oversight. Frequency of these 
site contacts varies depending on phase of the study (approximately weekly during enrollment 
& closeout, and monthly during maintenance). 
11.5 
Independent Data Monitoring Committee  
An independent data monitoring committee (IDMC) will be established to provide safety 
oversight for this study.  
The primary role of the IDMC will be to monitor ongoing safety data, provide recommendations 
to sponsor executive management to protect the safety of study subjects.  The IDMC members 
will be required to attend meetings on a regular basis.  The IDMC will be completely 
independent from sponsor and study personnel.  As part of the ongoing safety monitoring 
activities, the IDMC will have access to comparative results of safety and efficacy data (if 
necessary), aggregated by study arm.  

P17-1 (ProVent) Protocol  
PR-2677.02, 25 January 2019  
Page 67 of 78 
Dendreon Pharmaceuticals LLC 
 
 
Proprietary and Confidential 
The IDMC review of safety data will be conducted after the first 30 subjects have completed 
sipuleucel-T treatment.  Safety reviews will then be conducted approximately every 6 months 
during subject enrollment period and then annually until the last subject completes Biopsy 2.  
Study enrollment will not be suspended during IDMC review periods.  
11.6 
Quality Assurance 
A sponsor Quality Assurance auditor or designee may arrange and conduct visits to the clinical 
trial site to audit the performance of the study and the study documents originating at the site.  
The Principal Investigator will be informed of the outcome of audits. 
In addition, inspections by FDA, other regulatory authorities, or the IRB are possible at any 
time.  The Principal Investigator must inform sponsor of any such inspection immediately. 
The clinical trial site must provide direct access to source documentation and subjects’ medical 
records for audits and inspections. 
11.7 
Steering Committee 
The Steering Committee will be comprised of independent experts in the treatment of prostate 
cancer.  The Steering Committee will consult and advise regarding study design, protocol 
development and amendments, data analysis and interpretation, and scientific publications.   
11.8 
Disclosure of Data and Publication 
Publications and presentations proposed by clinical trial site personnel and/or principal 
investigator will be furnished to sponsor for review and comment pursuant to the terms of the 
clinical study agreement between the clinical trial site and sponsor.   
 

P17-1 (ProVent) Protocol  
PR-2677.02, 25 January 2019  
Page 68 of 78 
Dendreon Pharmaceuticals LLC 
 
 
Proprietary and Confidential 
12.0 
REFERENCES 
Antonarakis, 2017 
Antonarakis ES, Kibel AS, Yu EY et al. Sequencing of sipuleucel-T 
and androgen deprivation therapy in men with hormone-sensitive 
biochemically recurrent prostate cancer: A phase II randomized trial. 
Clin Cancer Res. (2017) 23(10):2451-2459. 
Borkhorst, 2015 
Bokhorst LP, Alberts AR, Rannikko A, et al. Compliance rates with the 
Prostate Cancer Research International Active Surveillance (PRIAS) 
protocol and disease reclassification in noncompliers. Eur Urol. (2015) 
68:814-821. 
Borkhorst, 2016 
Bokhorst LP, Valdagni R, Rannikko A, et al. A decade of active 
surveillance in the PRIAS study: An update and evaluation of the 
criteria used to recommend a switch to active treatment. Eur Urol. 
(2016) 70:954-960. 
Cooperberg, 2015 
Cooperberg MR and Carroll PR. Trends in management for patients 
with localized prostate cancer, 1990-2013. 
JAMA. (2015) 314(1): 80-82. 
Dall’Era, 2017 
Dall’Era MA, Albertsen PC, Bangma C, et al. Active surveillance for 
prostate cancer: A systematic review of the literature. Eur Urol. (2012) 
62:976-983. 
Epstein JI, 2017 
Epstein JI, Amin MB, Reuter VE, and Humphrey PA. Contemporary 
Gleason grading of prostatic carcinoma: An update with discussion on 
practical issues to implement the 2014 International Society of 
Urological Pathology (ISUP) Consensus Conference on Gleason 
grading of prostatic carcinoma. Am J Surg Pathol. (2017) 41:e1–e7 
FDA 2005 
Guidance for Industry: Good Pharmacovigilance Practices and 
Pharmacoepidemiologic Assessment. U.S. Department of Health and 
Human Services, Food and Drug Administration. Mar 2005. 
Fong, 2014 
Fong L, Carroll P, Weinberg V, et al. Activated lymphocyte recruitment 
into the tumor microenvironment following preoperative sipuleucel-T 
for localized prostate cancer. J Natl Cancer Inst. (2014) 106(11):1-9. 
Klotz, 2015 
Klotz L, Vesprini D, Sethukavalan P, et al. Long-term follow-up of a 
large active surveillance cohort of patients with prostate cancer. J Clin 
Oncol. (2015) 33(3): 272-277. 
Scher 2016 
Scher HI, Morris MJ, Stadler WM, et al. Trial design and objectives for 
castration-resistant prostate cancer: updated recommendations from the 

P17-1 (ProVent) Protocol  
PR-2677.02, 25 January 2019  
Page 69 of 78 
Dendreon Pharmaceuticals LLC 
 
 
Proprietary and Confidential 
prostate cancer clinical trials working group 3. J Clin Oncol. (2016) 
34:1402-1418. 
Siegel 2018 
Siegel R, Miller KD, and Jemal A. Cancer Statistics, 2018. Ca Cancer J 
Clin. (2018) 68:7–30. 
Sheikh, 2013 
Sheikh NA, Petrylak D, Kantoff PW, et al. Sipuleucel-T immune 
parameters correlate with survival: an analysis of the randomized phase 
3 clinical trials in men with castration-resistant prostate cancer. Cancer. 
Immunol Immunother. (2013) 62:137–147. 
Sipuleucel-T, 2017 
Sipuleucel-T prescribing information July 2017, Dendreon 
Pharmceuticals LLC 
 
 

P17-1 (ProVent) Protocol  
PR-2677.02, 25 January 2019  
Page 70 of 78 
Dendreon Pharmaceuticals LLC 
 
 
Proprietary and Confidential 
APPENDIX 1: 
EASTERN COOPERATIVE ONCOLOGY GROUP (ECOG) 
PERFORMANCE STATUS 
 
Grade 
 
Performance Criteria 
Karnofsky Scale 
Equivalent 
0 
Normal activity.  Fully active, able to carry on all 
predisease performance without restriction. 
90-100 
1 
Symptoms but ambulatory.  Restricted in physically 
strenuous activity but ambulatory and able to carry out 
work of a light or sedentary nature (e.g., light housework, 
office work). 
70-80 
2 
In bed < 50% of the time.  Ambulatory and capable of 
self-care, but unable to carry out any work activities.  Up 
and about more than 50% of waking hours. 
50-60 
3 
In bed > 50% of the time.  Capable of only limited self-
care, confined to bed or chair more than 50% of waking 
hours. 
30-40 
4 
100% bedridden.  Completely disabled.  Cannot carry on 
any self-care.  Totally confined to bed or chair. 
10-20 
5 
Dead 
0 
 
 
 

P17-1 (ProVent) Protocol  
PR-2677.02, 25 January 2019  
Page 71 of 78 
Dendreon Pharmaceuticals LLC 
 
 
Proprietary and Confidential 
APPENDIX 2: 
SHORT FORM-12 HEALTH SURVEY (SF-12)  
 
 
 

P17-1 (ProVent) Protocol  
PR-2677.02, 25 January 2019  
Page 72 of 78 
Dendreon Pharmaceuticals LLC 
 
 
Proprietary and Confidential 
APPENDIX 3: 
MEMORIAL ANXIETY SCALE FOR PROSTATE CANCER 
(MAX-PC) 
 

P17-1 (ProVent) Protocol  
PR-2677.02, 25 January 2019  
Page 73 of 78 
Dendreon Pharmaceuticals LLC 
 
 
Proprietary and Confidential 
APPENDIX 4: 
EXPANDED PROSTATE CANCER INDEX COMPOSITE FOR 
CLINICAL PRACTICE (EPIC-CP) 
 

P17-1 (ProVent) Protocol  
PR-2677.02, 25 January 2019  
Page 74 of 78 
Dendreon Pharmaceuticals LLC 
 
 
Proprietary and Confidential 
APPENDIX 5: 
THE INTERNATION PROSTATE SYMPTOM SCORE (I-PSS) 
 
 

P17-1 (ProVent) Protocol  
PR-2677.02, 25 January 2019  
Page 75 of 78 
Dendreon Pharmaceuticals LLC 
 
 
Proprietary and Confidential 
APPENDIX 6: 
NEW YORK CLASSIFICATION III-IV 
 
 
 
 

P17-1 (ProVent) Protocol  
PR-2677.02, 25 January 2019  
Page 76 of 78 
Dendreon Pharmaceuticals LLC 
 
 
Proprietary and Confidential 
APPENDIX 7: 
ACTIVE PHASE BIOPSY 1 & BIOPSY 2 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
Randomization 
Biopsy 1  
Systematic ≥10 cores 
      ± MRI targeted cores per PI discretion# 
*12-18 Months 
Biopsy 2  
Systematic ≥10 cores 
      ± MRI targeted cores per PI discretion# 
*33-39 Months 
*months from randomization 
# MRI targeted cores collected at 
baseline should be repeated for 
Biopsy 1 & Biopsy 2 
 

P17-1 (ProVent) Protocol  
PR-2677.02, 25 January 2019  
Page 77 of 78 
Dendreon Pharmaceuticals LLC 
 
 
Proprietary and Confidential 
APPENDIX 8: 
DETERMINATION OF ACTIVE HEPATITIS B  
 
Test 
Result 
Interpretation 
Hep B Surface Antigen (HBsAg) 
Hepatitis B Core Antibody (HBc Total) 
Hep B Surface Antibody(aHBs 2 Qual 
 
Negative 
Negative 
Negative 
Negative (not to exclude) 
Hep B Surface Antigen (HBsAg) 
Hepatitis B Core Antibody (HBc Total) 
Hep B Surface Antibody(aHBs 2 Qual) 
 
Negative 
Positive 
Positive 
Hep B infection resolved (not to exclude) 
Hep B Surface Antigen (HBsAg) 
Hepatitis B Core Antibody (HBc Total) 
Hep B Surface Antibody(aHBs 2 Qual) 
Negative 
Negative 
Positive 
 
Vaccinated and patient is immune to Hep 
B virus (not to exclude) 
Hep B Surface Antigen (HBsAg) 
Hepatitis B Core Antibody (HBc Total) 
Hep B Surface Antibody(aHBs 2 Qual) 
 
Positive 
Positive 
Negative 
Active HBV infection (Exclude) 
Hep B Surface Antigen (HBsAg) 
Hepatitis B Core Antibody (HBc Total) 
Hep B Surface Antibody (aHBs 2 Qual) 
 
Negative 
Positive 
Negative 
Distant resolved infection, or recovering 
from an acute infection, false positive or 
occult hepatitis B (Exclude) 
 
If aHBs2 Qual positive with or without HBc Total, patient is eligible. If HBsAg positive 
(regardless of all other HB panel results), patient is not eligible. All negatives are eligible as 
well. Isolated positive HBc Total is not eligible. 
 
 
 

P17-1 (ProVent) Protocol  
PR-2677.02, 25 January 2019  
Page 78 of 78 
Dendreon Pharmaceuticals LLC 
 
 
Proprietary and Confidential 
APPENDIX 9: 
DETERMINATION OF ACTIVE HEPATITIS C  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Testing Sequence for Identifying Active Hepatitis C   
Non Reactive 
Reactive 
HCV Antibody 
-
-
No HCV Detected 
HCV RNA 
No Current 
HCV 
infection 
-
Not 
Detected 
Current 
HCV 
infection 
Detected 
-
Screen 
Failure