This PowerPoint presentation demonstrates findings on a clinical trial of sipuleucel-T in HRPC patients to evaluate overall survival in this group. The FDA approval of Provenge was based on the results of IMPACT study.

1. Sipuleucel_T Immunotherapy for
Metastatic Prostate Cancer after Failing
Hormone Therapy
By Payam Javanmardi and Syeda Jamal
Academy of Applied Pharmaceutical Sciences
Canada, Toronto, December 2014
1

2. Prostate cancer is the most common noncutaneous
cancer among men in the United States and is the
second leading cause of death from cancer in men.
Localized prostate cancer may be cured with surgery
or radiation therapy, but the disease recurs in
approximately 20 to 30% of patients.
2

3. Androgen-deprivation therapy, the most common
treatment after recurrence, is effective, but the disease
eventually progresses in most patients who receive
such treatment.
On April 29, 2010 FDA approved Sipuleucel_T
(Provenge) to treat asymptomatic or minimally
symptomatic metastatic HRPC.
3

4. Sipuleucel-T is an active cellular Immunotherapy, a type
of therapeutic cancer vaccine, consisting of autologous
peripheral-blood mononuclear cells (PBMCs), including
antigen-presenting cells (APCs), that have been
activated ex vivo with a recombinant fusion protein
(PA2024).
PA2024 consists of a prostate antigen, prostatic acid
phosphatase, that is fused to granulocyte-macrophage
colony-stimulating factor, an immune cell activator.
4

5. 5

6. In a randomized, placebo-controlled trial involving 127
patients with metastatic castration resistant prostate
cancer, men in the sipuleucel-T group had a relative
reduction in the risk of death of 41%, as compared with
those in the placebo group.
A second randomized, placebo-controlled study showed
a trend toward increased survival with sipuleucel-T,
although it was not statistically significant.
6

7. These studies did not show a significant effect on the
time to progression, the primary end point of both trials.
To confirm these survival findings, the Immunotherapy
for Prostate Adenocarcinoma Treatment (IMPACT)
clinical study was conducted to support FDA approval.
7

8. Immunotherapy for Prostate Adenocarinoma
Treatment
ClinicalTrials.gov Identifier: NCT00065442
Study Type: Interventional
Study Design: Randomized, Double blind, Placebo-controlled in
Parallel Assignment across 75 clinical trial sites in USA and
Canada
Enrollment: 512
Start Date: July 2003
Study Completion Date: January 2009
Study Phase: Phase 3
Sponsor: Dendreon Corporation
Purpose: Provenge is an investigational product designed to
activate a man’s own antigen presenting cells, so that they can
detect prostate cancer cells and initiate an immune response
against them 8

9. Primary Outcome Measure:
 Overall Survival within a Time Frame from
randomization until death due to any cause by
means of a stratified Cox regression model
adjusted for baseline levels of serum prostate-specific
antigen (PSA) and Lactate
dehydrogenase
Secondary Outcome Measure:
Time to Objective Disease Progression was
monitored by means of computed tomography
(CT) at weeks 6, 14, 26, and 34 and every 12
weeks thereafter) 9

10. Intervention:
 Biological: Sipuleucel-T
Each dose of sipuleucel-T contains a minimum of 50 million
autologous CD54+ cells activated with a PAP-GM-CSF. A course
of therapy consists of 3 complete doses at approximately 2-
week intervals.
 Biological: APC-Placebo
Each dose of APC-Placebo contains approximately one-third of
the quiescent APCs prepared from a single leukapheresis
procedure. A course of therapy consists of 3 complete doses
given at approximately 2-week intervals.
10

11. Eligibility Criteria:
 Histologically documented adenocarcinoma of the prostate
 Cancer that has progressed while on adequate hormone
therapy This state of the disease is androgen independent
prostate cancer (AIPC)
 Cancer that has spread outside the prostate to lymph nodes
or bone
 The absence of or minimal current cancer-related pain
 Additionally Amended Criteria
 Male, 18 Years and older
11

12. Methods:
 512 patients randomly assigned in a 2:1 ratio to receive either
sipuleucel-T(341 patients) or placebo(171 patients) every 2 weeks,
for a total of three infusions
 Patients were scheduled for three leukapheresis procedures (at
weeks 0, 2, and 4), each followed approximately 3 days later by
infusion of sipuleucel-T or placebo
 Infusions of sipuleucel-T were prepared from PBMCs collected by
means of a single standard leukapheresis and then APCs were
cultured for 36 to 44 hours at 37°C with medial containing PA2024
 Placebo was prepared by culturing APCs from one third of the
leukapheresis collection in medium for 36 to 44 hours at 2 to 8 °C,
without PA2024
12

13. 13
Results: Participant Flow in Overall Study
APC-Placebo
Sipuleucel-T
Started 171 341
Completed 46 121
Not Completed 125 220
Lost to Follow-up 1 1
Death 121 (70.8%) 210 (61.6%)
Withdrawal by
Subject
3 9

14. 14
Results: Baseline Measures
APC-Placebo
Sipuleucel-
T
Total
Participants 171 341 512
Age
Mean ± SD
70.1 ± 9.0 71.1 ± 8.9 70.8 ± 8.9
Age
Median (Full
Range)
70
(40 to 89)
72
(49 to 91)
71
(40 to 91)
Gender
Female 0 0 0
Male 171 341 512

15. 15
Results: Primary Outcome Measure
APC-Placebo Sipuleucel-T
Participants 171 341
Overall Survival(Months)
95% Confidence Interval
21.7
17.7 to 23.8
25.8
22.8 to 27.7
Statistical Analysis 1 All groups
Method Regression, Cox
P Value 0.032
Hazard Ratio
95% Confidence Interval
0.775
0.614 to 0.979

16. 16
Results: Primary Outcome Measure
Statistical Analysis 2 All groups
Method Log Rank
P Value 0.023
Hazard Ratio
95% Confidence Interval
0.766
0.608 to 0.965

17. 17
Results: Secondary Outcome Measure
APC-Placebo Sipuleucel-T
Participants 171 341
Time to Objective
Disease Progression
(Weeks)
14.4 14.6
Statistical Analysis All groups
Method Log Rank
P Value 0.628
Hazard Ratio
95% Confidence Interval
0.951
0.773 to 1.169

18. AEs were reported for 496 of 506 (98%) and were mild to moderate for
330 patients (65.2%)
AEs that were reported more frequently in the sipuleucel-T group than
in the placebo group included chills, fever, headache, influenza-like
illness, myalgia, hypertension, hyperhidrosis, and groin pain
AEs that were reported more frequently in the placebo group included
anorexia, anxiety, depression, flank pain, and contusion as well as
hydronephrosis
Cerebrovascular events were reported as 2.4% and 1.8% in the
sipuleucel-T group and the placebo group, respectively
18
Results: Serious Adverse Events

19. More men in the sipuleucel-T group were alive 3 years after the
start of the study than men not treated with sipuleucel-T
Sipuleucel-T reduced the risk of death by 22.5% for patients
who received the vaccine
Only 1.5% of men discontinued treatment with sipuleucel-T due
to side effects
Provenge is the only personalized treatment that is clinically
proven to help extend life in certain men with advanced
prostate cancer
19
Conclusion

20. References
www.fda.gov
www.Clinicaltrials.gov
www.nejm.org
20