Safety, Pharmacokinetic and Proof-of-Concept Study of ARN-509 (Apalutamide) in Castration-Resistant Prostate Cancer (CRPC)

Percentage of participants with \>=50% decrease in PSA compared to baseline were assessed at Week 12. PSA progression was defined by the protocol-specific Prostate Cancer Working Group 2 (PCWG2) criteria: PSA increase greater than or equal to \[\>=\] 25 percent \[%\] and \>=2 nanogram per milliliter \[ng/mL\] above the nadir confirmed \>=3 weeks later; or \>=25% and \>=2 ng/mL above baseline PSA after 12 weeks.

Time frame: Week 12

Population: Modified intent-to-treat (mITT) population included all participants who received at least one dose of apalutamide and who were eligible for the cohort that they were enrolled in.

Time to PSA progression was measured as the time interval from the date of the first dose to the date of PSA progression as defined by the PCWG2 criteria. PCWG2 criteria: For participants who achieved \>=50% decrease from the baseline PSA, assessment of time to disease progression was when the PSA increased 25% and at a minimum of 2 ng/mL above the nadir at 3 or more weeks later. For participants without a PSA decrease, the time for progression was calculated at the time when the PSA progression was \>=25% and \>=2 ng/mL after 12 weeks.

Time frame: Up to approximately 7 years

Population: mITT population included all participants who received at least one dose of apalutamide and who were eligible for the cohort that they were enrolled in.

Objective Response Rate was defined as the percentage of participants with best overall response (OR) of confirmed complete response (CR) or partial response (PR) according to Response Evaluation Criteria in Solid Tumors, Version 1.0 (RECIST). Where, CR defined as disappearance of all target lesions. Any pathological lymph nodes must had reduction in short axis to less than 10 millimeter (mm). PR defined as at least 30 percent (%) decrease in sum of the diameters of the target lesions. Confirmed responses were those that persisted on repeat imaging study for at least 4 weeks after initial documentation of response.

Time frame: Up to approximately 7 years

Population: mITT population included all participants who received at least one dose of apalutamide and who were eligible for the cohort that they were enrolled in.

PFS was defined as the time from randomization to the radiographic disease progression or death, whichever occurred first. Radiographic progression defined by at least one of the following: a) Soft tissue progression by modified RECIST confirmed on repeat imaging \>= 6 weeks later; b) Progression by bone scans: 1) first bone scan with \>= 2 new lesions compared to baseline observed \<12 weeks from start date and confirmed on a second bone scan \>=6 weeks later that showed \>=2 additional lesions (a total of \>=4 new lesions compared to baseline); or 2) first bone scan with \>=2 new lesions compared to baseline observed \>=12 weeks from start date and the new lesions verified on the next bone scan \>=6 weeks later (a total of \>=2 new lesions compared to baseline).

Time frame: Up to approximately 7 years

Population: mITT population included all participants who received at least 1 dose of apalutamide and who were eligible for cohort that they were enrolled in. PFS results are reported for Dose Escalation Cohort (Phase 1) and cohort 2, 3 (Phase 2) as no PFS analysis was performed for Cohort 1 of Phase 2 per planned analysis.

MFS was defined as the time from the start of treatment until new metastatic lesions were observed on Computed Tomography/ Magnetic Resonance Imaging (CT/MRI) scans or radionuclide bone scans (according to PCWG2 criteria: appearance of \>=2 new lesions, and, for the first reassessment only, a confirmatory scan performed 6 or more weeks later that showed at least 2 or more additional new lesions) or death, whichever occurred first.

Time frame: Up to approximately 7 years

Population: mITT population included all participants who received at least 1 dose of apalutamide and were eligible for cohort that they were enrolled in. MFS results are reported for Cohort 1 (Phase 2) participants only as MFS analysis was not performed for other cohorts that is Dose Escalation Cohort (Phase 1) and Cohort 2, 3 (Phase 2) per planned analysis.