Presurgical Study of Daratumumab (CD38 Antagonist) or JNJ-40346527 in Men With High-Risk Localized Prostate Cancer Followed by Radical Prostatectomy

Study Groups:

If you are found to be eligible to take part in this study, you will be assigned to 1 of 2
study arms (groups) based on how many participants are enrolled in each arm.

- If you are assigned to Arm A, you will receive daratumumab.

- If you are assigned to Arm B, you will receive JNJ-527.

The study doctor will tell you which arm you have been assigned.

Study Drug Administration:

If you are in Arm A, you will receive daratumumab by vein 1 time each week for 4 weeks before
your prostatectomy. During Week 1, your dose of daratumumab will be given over 8 hours. After
that, each dose will be given over about 4 hours.

In this study, the following will be done to lower the chance of a daratumumab infusion
related reaction:

- You will get medications, including steroids, acetaminophen, and/or antihistamine before
the infusion. If you are considered high risk, you may also get medications, including
inhaled steroids, after the infusion.

- The infusion may be slowed down or stopped if you have a reaction.

- You may stay overnight in the hospital after the infusion so the study staff can check
your health.

You may ask the study staff for more information about the types of medications you will
receive to lower your chance of an infusion-related reaction, including how they are
administered and their risks.

If you are in Arm B, you will receive JNJ-527 by mouth 2 times each day for up to 4 weeks.

Length of Study:

You may receive up to 4 doses of daratumumab or up to 4 weeks of JNJ-527. You will no longer
be able to take the study drug if the disease gets worse, if intolerable side effects occur,
or if you are unable to follow study directions.

Your participation on the study will be over after the Week 18 visit (described below).

Study Visits:

During Weeks 1-4:

- You will have a physical exam

- Blood (about 2 tablespoons) will be drawn for routine and blood type testing (if you are
in Group A). Daratumumab treatment will interfere with blood type testing which is
needed before blood transfusions can be given. For this reason, a test to find out your
blood type will be performed before you receive daratumumab. You should carry the blood
type card with you while you are on this study.

- During Week 3 only, blood (about 1-2 teaspoons) will be drawn to check your PSA levels.

During Week 5 or 6 (the week of your surgery based on your study drug):

- You will have a physical exam

- Blood (about 2 tablespoons) will be drawn for routine tests, including measurements of
your PSA and testosterone levels. Part of this sample will also be used for blood type
testing.

- You will have surgery to remove your prostate. You will sign a separate consent form
explaining the procedure and its risks in more detail.

End-of-Study Visit:

During Week 18, blood (about 2 tablespoons) will be drawn for routine tests, including
measurements of your PSA and testosterone levels.

If you withdrew from the study before Week 18, the study staff may call you to ask how you
are doing. This call should last about 5-10 minutes.

Inclusion Criteria:

1. Consent to MD Anderson laboratory protocol PA13-0291.

2. Histological documentation of adenocarcinoma of the prostate reviewed at MD Anderson
Cancer Center. Patients with small cell, neuroendocrine, or transitional cell
carcinomas are not eligible.

3. Patients with high-risk prostate cancer (at least 1 core with Gleason sum >/=8) must
have at least three core biopsies involved with cancer (a minimum of 6 core biopsies,
must be obtained at baseline). A prostate biopsy within 3 months from screening is
allowed for entry requirements.

4. No evidence of metastatic disease as documented by technetium-99m (99mTc) bone scan
and by computed tomography (CT) or magnetic resonance imaging (MRI) scans.

5. Eugonadal state (serum testosterone >150 ng/dL).

6. Localized or locally advanced disease deemed by the surgeon to be resectable. Patients
must be appropriate candidates for radical prostatectomy plus pelvic lymph node
dissection

7. No prior treatment for prostate cancer including prior surgery (excluding
transurethral resection of the prostate [TURP]), cryoablation, pelvic lymph node
dissection, radiation therapy, hormonal therapy or chemotherapy.

8. Subject must be >/=18 years of age.

9. To avoid risk of drug exposure through the ejaculate (even men with
vasectomies),subjects must use a condom during sexual activity while on study drug and
for 3 months following the last dose of study drug. If the subject is engaged in
sexual activity with a woman of childbearing potential, a condom is required along
with another effective contraceptive method consistent with local regulations
regarding the use of birth control methods for subjects participating in clinical
studies and their partners. Donation of sperm is not allowed while on study drug and
for 3 months following the last dose of study drug.

10. ECOG performance status (PS) grade of 0 or 1.

11. Clinical laboratory values at screening: 1) Hemoglobin, platelet count, absolute
neutrophil count, absolute lymphocyte count within institutional normal limits.
Administration of growth factors or blood transfusions will not be allowed to confirm
eligibility 2) Serum chemistries, renal and liver panels within institutional normal
limits or meets the requirements for radical prostatectomy

12. Each subject must sign an informed consent form (ICF) indicating that he understands
the purpose of and procedures required for the study and is willing to participate in
the study.

Exclusion Criteria:

1. Prior hormone therapy for prostate cancer including orchiectomy, antiandrogens,
ketoconazole, or estrogens (5-alpha reductase inhibitors allowed), or LHRH
agonists/antagonists.

2. Currently enrolled in another interventional study.

3. Concurrent treatment with systemic corticosteroids (prednisone dose >10 mg per day or
equivalent) or other immunosuppressive drugs <14 days prior to treatment initiation.
Steroids that are topical, inhaled, nasal (spray), or ophthalmic solution are
permitted.

4. History of or known or suspected autoimmune disease (exception(s): subjects with
vitiligo, resolved childhood atopic dermatitis, hypothyroidism, or hyperthyroidism
that is clinically euthyroid at screening are allowed).

5. Known evidence of an active infection requiring systemic therapy such as human
immunodeficiency virus (HIV), active hepatitis, or fungal infection.

6. History of clinically significant cardiovascular disease including, but not limited
to: 1) Myocardial infarction or unstable angina initiation 2) Clinically significant cardiac arrhythmia 3) Deep vein thrombosis,
pulmonary embolism, stroke heart failure (New York Heart Association class III-IV) 5) Pericarditis/clinically
significant pericardial effusion 6) Myocarditis 7) Endocarditis

7. History of major implant(s) or device(s), including but not limited to: 1) Prosthetic
heart valve(s) 2) Artificial joints and prosthetics placed treatment initiation 3) Current or prior history of infection or other clinically
significant adverse event associated with an exogenous implant or device that cannot
be removed

8. Other prior malignancy (exceptions: adequately treated basal cell or squamous cell
skin cancer, superficial bladder cancer, or any other cancer in situ currently in
complete remission)
9. Any medical, psychological or social condition that in the opinion of the
investigator, would preclude participation in this study.