Armor3-SV: A Phase 3, Randomized, Open Label, Multicenter, Controlled Study of Galeterone Compared to Enzalutamide in Men Expressing Androgen Receptor Splice Variant-7 mRNA (AR-V7) Metastatic (M1) Castrate Resistant Prostate Cancer (CRPC)

SUMMARY

The primary purpose of this research study will be to compare the time it takes for tumors to grow based on

radiological studies in patients who receive galeterone compared to a standard treatment enzalutamide, which

is approved in some countries such as the USA. Patients like you who have CRPC and evidence of tumor that

has spread to other parts of the body, known as metastatic disease and also have the abnormal androgen

receptor known as AR-V7 may be enrolled. This study will also compare other effects between the two

treatments such as quality of life, degree of pain, the time it takes before starting another cancer therapy,

decreases in PSA and evaluation of tumor shrinkage. The study will also determine how long patients live

following each treatment.

The study will be in adult male patients who meet the following criteria:

Have AR-V7 (abnormal androgen receptor) present in their circulating tumor cells (CTCs) in blood

Have metastatic CRPC (meaning the tumor has spread beyond the local prostate area to other parts of the body)

Have not yet received abiraterone (an FDA or other country approved drug) or enzalutamide (an FDA or other country) approved drug

Only patients who test positive for the AR-V7 abnormal form of the androgen receptor can take part in the

study and this will be identified by an initial blood test.

If you test positive for AR-V7, then you will be randomly assigned to receive either galeterone (2550 mg

total dose in tablet form) or enzalutamide (160 mg total dose in capsule form); neither you nor your doctor

will have any choice of the drug group to which you are assigned. Both of the drugs will be known as

‘study drug’ in this document. The treatment you receive will be determined like a ‘flip of a coin’ with

approximately half of the patients receiving galeterone and half receiving enzalutamide. Both you and

your study doctor will know what treatment you are assigned to receive. Because this is a research study,

galeterone or enzalutamide will be given at no cost to you only during this study and not after the study is

over.

If you are assigned to receive galeterone in this study, the tablets that you will be taking have been

manufactured in a different way than the capsules that were used in previous studies. It was shown that

depending on whether the capsules were taken with food or not there was an effect on how the drug was

taken up into the body. This is called a “food effect”. The new tablet form of galeterone will not have a

“food effect” and therefore will make taking the drug more convenient since you may take it with or

without food.

Tokai Pharmaceuticals plans to conduct the ARMOR3-SV study, which will be a study of galeterone (an

investigational compound) compared to a drug, enzalutamide (which is approved in some countries, such

as USA, and is commonly used in mCRPC). The study is being conducted in men with mCRPC that have

splice variant (an abnormal form) of the androgen receptor (called AR-V7 splice variant) which

contributes to prostate cancer growth and has been linked with lack of response to certain FDA approved

prostate cancer therapies. You will have had an initial blood test to see if you are positive for this

abnormal form of the androgen receptor.

Prostate cancer tumor growth is, in part, related to something called the androgen receptor. The androgen

receptor is a protein found in prostate cancer cells. When the androgen receptor attaches to the male sex

hormone, testosterone, it sends a signal that makes the tumor cells grow and increases the levels of

prostate specific antigen in the blood or PSA. Testosterone is primarily produced by the testes.

While there are many ways of blocking testosterone production or action such as surgical removal of the

testes (castration) or with medication like Lupron® or with androgen deprivation therapy (ADT) such as

Casodex®, most patients will still develop tumor growth indicated by an increase in PSA, an increase in

tumor size, new areas of tumor spread in the body called metastases and new disease related symptoms

such as pain.

Prostate cancer that no longer responds to these treatments is in part due to the production of testosterone

by the prostate cancer itself, and also by production in the adrenal glands. The growth and progression of

prostate cancer even after surgical removal of the testes or after treatment with medications that block the

production of testosterone is called castrate resistant prostate cancer or CRPC. In addition, at times, it is

believed that the cancer becomes much more responsive and can grow in the presence of very low levels

of testosterone. In such situations other agents approved in the USA and other countries that interfere with

testosterone production (abiraterone) or block testosterone binding to the androgen receptor

(enzalutamide) can be used. These agents are effective in most patients, but only for a limited time

(usually months), before the prostate tumor starts to grow again. In addition, in a clinical study, these

agents have been shown not to be very effective in patients who have CRPC that has the AR-V7 androgen

receptor abnormality. This lack of efficacy suggests that the presence of this abnormal form of the

androgen receptor acts like a light switch that is always “on” signaling the cancer to grow, so lowering

testosterone (with agents like abiraterone) does not have an effect and because the abnormal form of the

androgen receptor has an abnormal structure it no longer binds with the other androgen receptor inhibitors

(with agents like enzalutamide). This research study with galeterone is specifically addressing castrate

resistant prostate cancer bearing the AR-V7 androgen receptor abnormality.

Galeterone is an investigational agent that has been shown in animal studies to reduce the size of prostate

cancer tumors. These animal tests and other laboratory tests suggest that galeterone can impact the

prostate cancer tumor in three ways:

It makes it harder for the prostate cancer cells to make testosterone.

It prevents whatever testosterone is still around from attaching to the androgen receptor, even

when the androgen receptor has undergone an abnormal alteration (such as the splice variant

AR-V7).

It reduces the number of androgen receptors present in the prostate cancer tumor.

Together, these three actions of galeterone may deprive the prostate cancer tumor cells of what they need

in order to grow.

As of September 4, 2014 galeterone has been tested in 254 people. This includes 49 prostate cancer

patients who received daily oral doses of galeterone of up to 2600 mg for up to 20 months in a previous

study (TOK-200-05, ARMOR1), and 121 prostate cancer patients in the current ongoing study (TOK-

200-10, ARMOR2). In clinical studies, galeterone has shown reductions in PSA and the tumor in CRPC

patients. Additionally, in the ongoing ARMOR2 trial, there is early data showing decreases in PSA by at

least half in patients that have abnormalities in the androgen receptor which may include AR-V7.

COH Protocol Number : 15134

ClinicalTrials.gov Number : NCT02438007

Principal Investigator : Twardowski, Przemyslaw M.D.

Sponsor : Tokai Pharmaceuticals, Inc.

BRIEF ELIGIBILITY CRITERIA :

Eligible Ages : >=18

Gender : Male

Minimum Performance Status : ECOG/SWOG:1

Treatment Intent : Non-Adjuvant treatment

Prior Chemotherapy :

Brain Metastases :

Measurable Disease :