This is a Phase Ib, open label study of ARN-509 administered in combination with abiraterone acetate and prednisone in patients with metastatic castration-resistant prostate cancer.

Key Inclusion Criteria:

• Participants must have histologically confirmed prostate cancer.
• Radiographic evidence of metastatic disease, detectable by bone scan, CT scan, or MRI. At least one site of metastatic disease must be amenable to needle biopsy.
• Castrate levels of testosterone (testosterone < 50 ng/dL) on androgen deprivation therapy (ADT). Patients who have not undergone orchiectomy will continue gonadotropin releasing hormone (GnRH) agonist or antagonist therapy.
• Age > 18 years
• ECOG performance status < 2
• Evidence of disease progression on ADT. Patients must have two serial rises in PSA from nadir, with at least 1 week between PSA measurements, with a minimum PSA of 2 ng/mL, OR patients must have radiographic evidence of progression. Nadir is defined as the lowest PSA value after beginning the most recent therapy for metastatic CRPC.

Key Exclusion Criteria:

• Participants who have had chemotherapy or radiotherapy within 4 weeks prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier.
• Participants may not be receiving any other study agents.
• Participants with known brain metastases
• Any history of seizure or a condition that may pre-dispose to seizure (e.g., prior stroke within 1 year prior to randomization, brain arteriovenous malformation, Schwannoma, meningioma, or other benign CNS or meningeal disease which may require treatment with surgery or radiation therapy).
• Concurrent therapy with medications known to have seizure potential (those must have been discontinued or substituted for at least 28 days prior to starting the trial)
• Concurrent treatment with strong CYP3A4 inhibitors (e.g., ketoconazole, itraconazole, clarithromycin, atazanavir, indinavir, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin, voriconazole, grapefruit juice) or inducers (e.g., dexamethasone, phenytoin, carbamazepine, rifampin, rifabutin, rifapentin, phenobarbital, St. John's Wort)
• History of pituitary dysfunction
• History of adrenal dysfunction
• Requirement for steroid use greater than 10 mg of prednisone daily
• History of gastrointestinal disorder or prior extensive gastrointestinal surgery that may interfere with sufficient absorption of the study compounds.
• Prior history of CYP17 inhibitors (e.g., abiraterone acetate, TAK-700) and second-generation anti-androgen (e.g., MDV3100)