A Study of Niraparib Combination Therapies for the Treatment of Metastatic Castration-Resistant Prostate Cancer

This multicenter study will evaluate safety and efficacy of niraparib in combination with
other anti-cancer agents. Two combinations are being studied: the first combination study
will combine niraparib with the anti-programmed cell death protein (PD)-1 monoclonal
antibody, JNJ-63723283 in participants with metastatic castration-resistant prostate cancer
(mCRPC). The second combination will combine niraparib with abiraterone acetate plus
prednisone (AA-P) in mCRPC participants with DNA-repair gene defects (DRD). Combination 1 has
2 parts: in Part 1 (dose selection), participants will be enrolled to explore 2 doses of
niraparib and JNJ-63723283; and Part 2 (dose expansion) will evaluate the combination therapy
in an expanded number of participants. In Part 2, participants will be enrolled into 2
cohorts based on biomarker status. Combination 2 has only 1 part (Part 2) and no Part 1. In
Part 2, participants will be enrolled into 4 cohorts (breast cancer gene [BRCA] biallelic
loss [2A], other DRD biallelic loss [2B], BRCA monoallelic loss [2C], and other DRD
monoallelic loss [2D]). Each combination in the study will have 4 phases: A Prescreening
Phase, a Screening Phase, a Treatment Phase, and a Follow-up Phase. Study evaluations will
include efficacy, pharmacokinetic (PK), PK/pharmacodynamics, biomarkers, safety and
tolerability.

Inclusion Criteria:

- Participants willing to undergo all protocol-specified biopsies

- Diagnosis of prostate adenocarcinoma as confirmed by the investigator

Combination 1:

- Must have determination of biomarker (BM) status for DNA-repair gene defects (DRD)
(either BM positive [+] or BM negative [-]) by the sponsor's blood or tissue assay

- Participants must have measurable disease as defined by response evaluation criteria
in solid tumors (RECIST) 1.1 (soft tissue lesion of greater than or equal to (>=) 10
millimeter (mm) in the long axis or extrapelvic lymph node of >=15 mm in the short
axis)

- Must have previously received at least 1, but no more than 2, lines of novel androgen
receptor (AR)-targeted therapy (that is, abiraterone acetate with prednisone,
enzalutamide) for metastatic castration-resistant prostate cancer (mCRPC).
Participants must have had at least 4 weeks of AR-targeted therapy

Combination 2:

- Must be biomarker positive for DRD by either the sponsor's blood or tissue assay

- Must have progressed on 1 prior line of novel AR-targeted therapy (that is,
abiraterone acetate with prednisone, enzalutamide) for mCRPC. Prior treatment with
taxane-based therapy and AR-targeted therapy outside of the mCRPC setting is allowed

Exclusion Criteria:

- Prior treatment with a poly (adenosine diphosphate [ADP]-ribose) polymerase (PARP)
inhibitor

- History or current diagnosis of myelodysplastic syndrome (MDS)/acute myeloid leukemia
(AML)

- Active malignancy (exceptions: adequately treated basal cell or squamous cell skin
cancer, superficial bladder cancer, or any other cancer in situ currently remission)
less than or equal to (<=) 2 years prior to enrollment

- Active infection requiring systemic therapy

- Allergies, hypersensitivity, or intolerance to niraparib or the corresponding
excipients