An Efficacy and Safety Study of JNJ-56021927 (Apalutamide) in High-risk Prostate Cancer Subjects Receiving Primary Radiation Therapy: ATLAS

This is a randomized, double-blind, placebo-controlled, multicenter study of apalutamide plus
GnRH agonist compared with GnRH agonist among participants with high-risk, localized or
locally advanced prostate cancer receiving primary radiation therapy (RT). The study will
include a Screening Phase, Treatment Phase, a Posttreatment Phase, and a Long-term Follow-up
Phase. Participants will either receive either apalutamide (experimental) or bicalutamide 50
milligram (mg) capsule plus placebo as control group. Safety will be monitored throughout the
study.

Inclusion Criteria:

- Age >= 18 years

- Indicated and planned to receive primary radiation therapy for prostate cancer

- Histologically confirmed adenocarcinoma of an intact prostate, and 1 of the following
at diagnosis: 1) Gleason score >=8 and >=cT2c, 2) Gleason score >=7, PSA >=20 nanogram
per milliliters (ng/mL), and >=cT2c

- Charlson index (CCI) <=3

- An Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) grade of 0 or 1

- Adequate organ function: (1) aspartate aminotransferase (AST), alanine
aminotransferase (ALT), within normal limits (WNL), (2) serum creatinine less than (<)
1.5 milligram/deciliter (mg/dL) (<133 micromoles/Liter [mcmol/L]), (3) platelets
greater than or equal to (>=)140,000/microLiter (mcL), independent of transfusion
and/or growth factors within 3 months prior to randomization, (4) Hemoglobin >= 12.0
gram/deciliter (g/dL) (7.4 millimloes [mmol], independent of transfusion and/or growth
factors within 3 months prior to randomization

- Participants who are sexually active (even men with vasectomies) and willing to use a
condom and agree not to donate sperm during the trial

- Signed, written, informed consent

- Be able to swallow whole study drug tablets

Exclusion Criteria: -

- Presence of distant metastasis, (clinical stage M1). Isolated pelvic nodal disease
below the iliac bifurcation (clinical stage N1) is not an exclusion. Diagnosis of
distant metastasis (clinical M stage; M0 versus M1a, M1b, M1c) and pelvic nodal
disease (clinical N stage; N1 versus N0) will be assessed by central radiological
review. Patients are considered eligible only if the central radiological review
confirms clinical stage M0.

- Prior treatment with gonadotropin releasing hormone (GnRH) analogue or anti-androgen
or both for >3 months prior to randomization

- Bilateral orchiectomy

- History of pelvic radiation

- Prior systemic (example [e.g.], chemotherapy) or local (e.g. radical prostatectomy,
cryotherapy) treatment for prostate cancer

- History of seizure or any condition that may predispose to seizure (including, but not
limited to prior stroke, transient ischemic attack or loss of consciousness <= 1 year
prior to randomization; brain arteriovenous malformation; or intracranial masses such
as schwannomas and meningiomas that are causing edema or mass effect)

- Prior treatment with enzalutamide, abiraterone acetate, orteronel, galeterone,
ketoconazole, aminoglutethimide, estrogens, megestrol acetate, and progestational
agents (including cyproterone acetate) for prostate cancer

- Prior treatment with radiopharmaceutical agents (e.g., strontium-89) or immunotherapy
(e.g., sipuleucel-T) for prostate cancer

- Prior treatment with systemic glucocorticoids ≤4 weeks prior to randomization or is
expected to require long-term use of corticosteroids during the study

- Use of 5-alpha reductase inhibitors (e.g., dutasteride, finasteride) <=4 weeks prior
to randomization

- Use of any investigational agent <=4 weeks prior to randomization

- Current chronic use of opioid analgesics for >=3 weeks for oral or >7 days for
non-oral formulations

- Major surgery <=4 weeks prior to randomization

- Current or prior treatment with anti-epileptic medications for the treatment of
seizures

- Gastrointestinal conditions affecting absorption

- Known or suspected contraindications or hypersensitivity to apalutamide, bicalutamide
or GnRH agonists or any of the components of the formulations

- Any condition for which, in the opinion of the investigator, participation would not
be in the best interest of the subject