PROSPECT

African American Men and Prostate Cancer Management

Option for Clinical Trial Participation in an

Immunotherapy Study

Jennifer Harris, PharmD

Medical Science Liaison

Bavarian Nordic, Inc.

Prostate Cancer: Overview

• Overall the most common cancer in men of all races

• One in six American men of all races will develop prostate

cancer in their lifetime

• One in thirty three men will die of prostate cancer

• The second most common cause of cancer-related death in

men of all races

• The incidence of prostate cancer is expected to rise (aging

population)

Source: U.S. Cancer Statistics Working Group. United States Cancer Statistics: 1999–2009 Incidence

and Mortality Web-based Report. Atlanta (GA): Department of Health and Human Services, Centers

for Disease Control and Prevention, and National Cancer Institute; 2013. Available at:

http://www.cdc.gov/uscs.

2012 Prostate Cancer Facts African Americans

Source: American Cancer Society; Cancer Facts & Figures

For African Americans 2011-2012

• There were approximately 35,110 cases of prostate cancer among African American men in 2011, accounting for 40% of all cancers diagnosed in African American men. • Between 2003-2007, the average annual prostate cancer incidence rate among African American men was 229.4 cases per 100,000 men, which was 60% higher than the incidence in white men • The only well-established risk factors for prostate cancer are age, race, and family history of the disease. • African American men and Jamaican men of African descent have the highest prostate cancer incidence rates worldwide. • The reasons for this are not clear, but may in part reflect genetic factors that vary in populations originating in different parts of the world

Possible Reasons for differences in stage of

disease at diagnosis and mortality African American vs. White Americans

• Less frequent access to health care (less frequent PSA screening)

• Lower quality care (less treatment options)

• Genetic predisposition

• Biological factors (higher PSA levels, difference is diet)

• More aggressive disease – due to later detection?

• More aggressive disease – due to genetic and biology?

Natural History of Prostate Cancer PROSTVAC-VF in pre-Chemotherapy Setting of mCRPC

Tu

mo

r v

olu

me

an

d

act

ivit

y

Hormone dependent Castration-resistant

No pain Pain (“symptomatic”)

Death Start of chemotherapy

Hormone treatment

(Androgen Ablation)

Local treatment

Non-metastatic Metastatic

Immunotherapy

Localized

HSPC

Non-metastatic

CRPC (D0.5)

Metastatic

CRPC Recurrent

HSPC

15–20 years

What is Immunotherapy?

Immunotherapy stimulates the immune system to help fight

foreign invaders and other conditions including cancer. This can be

accomplished by using a vaccine, antibody therapy, or non specific

immunotherapies.

The body's immune system reacts to antigens. Antigens are

anything that causes the immune system to respond, like germs,

viruses, and parasites or tumor antigens. When an antigen is found,

the response of the immune system is to kill the antigen and

anything it may be attached to.

Prostate Cancer A Good Target for an Immunotherapeutic Approach with a

Cancer Vaccine

• Prostate cancer is generally slow-growing

Time to generate a specific immune response

• Limited tolerability of chemotherapy in elderly men with prostate cancer

Less use of immunosupressive chemotherapy

Limited number of standard treatments for metastatic disease

• Unique tumor-associated antigen (PSA) to create targeted anti-tumor

effect

Tumor burden – patient selection

Treatment response

Participation in Clinical Trials

African Americans

Questions Response

In general, do less African

Americans participate in

Clinical Trials than White

Americans?

In a recent poll, only 27 percent of black American

respondents were willing to participate in a clinical trial,

versus 39 percent of white respondents.

Why don’t more African

Americans participate in

clinical Trials?

There is a general distrust of the medical/healthcare system

amongst some African Americans, and perhaps many,

based on personal experience. In addition, historical events

have given African Americans reason to mistrust clinical

trials.

How can a person be sure

that a clinical trial is safe?

An Institutional Review Board (IRB) must approve all studies

involving human or animal subjects in advance. An IRB's

main responsibility is to protect the public from harm and

look carefully at each study's methods to make sure the

research is safe,

Does drug effectiveness

vary across races?

Some drugs, like ACE inhibitors, have been shown through

clinical trials to be less effective in African Americans. To be

sure, there needs to be sufficient numbers of patients of all

races represented in a clinical trial population.

PROSTVAC-VF

PSA

Vaccines:

(rV-PSA-TRICOM)

(rF-PSA-TRICOM)

What is PROSTVAC-VF Immunotherapy?

Tumor antigen gene Costimulatory molecule genes

Induction of tumor-

specific immune

responses (T-cells)

PROSTVAC-VF Therapeutic Prostate Cancer Vaccine Candidate

• PROSTVAC-VF is comprised of 2 component viral vectors:

o A recombinant vaccinia virus (PROSTVAC-V) to prime the immune system

o A recombinant fowlpox virus (PROSTVAC-F) to boost immune response

• PROSTVAC-VF is delivered through 7 subcutaneous injections:

o One priming vaccination

o Six booster vaccinations (monthly)

• PROSTVAC-VF is designed to induce immune responses specifically

directed against prostate cancer cells

PROSTVAC-VF

Randomized Phase II Study

PROSTVAC-VF Phase 2 Randomized Controlled Study Design

Asymptomatic

Minimally symptomatic

Metastatic

Castration Resistant

Prostate Cancer

PROSTVAC-VF

+ GM-CSF

Empty Vector

+ Placebo

P

R

O

G

R

E

S

S

I

O

N

Treated at

physician

discretion

Treated at physician discretion

S

U

R

V

I

V

A

L

Crossover

PROSTVAC-VF Randomized Phase 2 Endpoints

Primary endpoint:

• Progression-free survival at 6 months

Results:

• No impact on short-term progression-free survival

• No marked impact on PSA

Secondary endpoints:

• Overall survival, time to onset of opioid use, quality of life

PROSTVAC-VF Randomized Phase 2

Overall Survival Results

p=0.0061

Δ 8.5 months

N Deaths Median

Control 40 37 16.6

PROSTVAC® 82 65 25.1

Hazard ratio

0.56 (95% CI 0.37–0.85)

Survival

(% of patients)

Significantly extended overall survival

0 12 24 36 48 60

0

20

40

60

80

100

Months

Reference: Kantoff et al., Journal of Clinical Oncology, January 2010

16.6 Months

25.1 Months

PROSTVAC-VF Randomized Phase 2 Common Adverse Events – Well Tolerated

Adapted from Kantoff et al., JCO 2010

Adverse Event (%) PROSTVAC-VF (n = 82) Control (n = 40)

Injection Site Reactions

Erythema 58.5 55.0

Pain 35.4 35.0

Swelling 28.0 12.5

Pruritus 20.7 10.0

Induration 12.2 15.0

General Disorders

Fatigue 42.7 20.0

Pyrexia 18.3 15.0

Peripheral Edema 13.4 10.0

Chills 14.6 2.5

GI Disorders

Constipation 11.0 15.0

Diarrhea 8.5 15.0

Nausea 20.7 5.0

Musculoskeletal & Connective Tissue Disorders

Arthralgia 12.2 25.0

Nervous System Disorders

Dizziness 12.2 7.5

PROSPECT

Global Phase 3 PROSTVAC-VF Clinical Study

PROSPECT A Global Clinical Study for Metastatic Prostate Cancer

• Study size

• 1,200 patients

• Up to 250 sites

• 13 countries and counting

• Study duration

• 5 months treatment period

• Long Term Follow Up

• Principal Investigators:

• Lead PI: Dr. James Gulley, National Cancer Institute

• Co-PI: Dr. Phil Kantoff, Dana-Farber Cancer Institute

PROSPECT US sites (active)

PROSPECT Who is eligible to participate?

• Documented asymptomatic or minimally symptomatic mCRPC

• Documented bone metastases and/or lymph node metastases

• No other metastases

• No scheduled opioid narcotics for persistent cancer-related pain

• Have not yet received chemotherapy

• Life expectancy > 1 year

PROSPECT Endpoints

Primary Efficacy Endpoint Overall survival

Secondary Efficacy Endpoint

Proportion of event-free patients at

six months compared to placebo

Safety Endpoints

Number of adverse events compared

to placebo

PROSPECT Phase 3 Clinical Study Design

Non/Minimally

symptomatic

metastatic

Castration

Resistant

Prostate Cancer

N = 1200

(1:1:1)

A PROSTVAC-VF +

low dose adjuvant GM-CSF

C Vector Placebo

S

U

R

V

I

V

A

L

B PROSTVAC-VF

Long

Term

Follow

Up

FDA-approved study design

Three-arm study evaluating overall survival in two separate comparisons:

• The investigational vaccine plus low dose adjuvant GM-CSF (A) versus control (C)

• The investigational vaccine without GM-CSF (B) versus control (C)

Wk1 Wk3 Wk5 Wk9 Wk13 Wk17 Wk21

PROSTVAC-V

or Placebo

PROSTVAC-F or Placebo

1 s.c. Prime 6 s.c. Boosts

PROSPECT PROSTVAC-VF Treatment Schedule

Adjuvant GM-CSF (low-dose: 100 µg) or Placebo s.c. Day 1- 4 for each administration

5 mo

Participation of African Americans

PROSTVAC-VF Randomized Studies Participation of African Americans

• 11.5% in the PROSTVAC phase 2 trial were Black men

• 6% Black men in Sipuleucel-T registration trial1

• ~10% Black men currently enrolled in ongoing PROSTVAC phase

3 trial

• Can participation be increased?

1Kanthoff et al., NEJM 2010

Minority Recruitment

• Enroll African American patients up to the level of representation in

the general US population (13.6%, 2010 US census)

• Target study centers in the areas of high African American

populations (Georgia, Louisiana, North Carolina, South Carolina)

• Tailor advertising and recruitment tools to African American

groups

• Enlist the help of patient advocacy groups

Minority Recruitment Goals