A Study of Cetrelimab (JNJ-63723283), a Programmed Cell Death Receptor-1 (PD-1) Inhibitor, Administered in Combination With Apalutamide in Participants With Metastatic Castration-Resistant Prostate Cancer

This study is of participants originally diagnosed with adenocarcinoma of the prostate who
have now developed mCRPC and who have progressed on therapy with abiraterone acetate plus
prednisone/prednisolone (AA-P), apalutamide, or enzalutamide. Participants with
treatment-emergent small-cell neuroendocrine prostate cancer (t-SCNC) assessed by the
screening biopsy may be considered for this study. Participants must have confirmed
prostate-specific antigen (PSA) progression per Prostate Cancer Clinical Trials Working Group
(PCWG3) criteria. The primary hypothesis is that treatment with cetrelimab and apalutamide is
safe and leads to improvement in the 12-week PSA response rate. The study consists of
Screening period (28 days prior to Cycle 1 Day 1), Treatment Period, End-of-Treatment Visit
(performed after the last dose of study drug is administered), and Follow-up Period
(participants will have Follow-up assessment every 12 weeks after the End-of-Treatment
Visit). The efficacy, safety, and pharmacokinetics of cetrelimab in combination with
apalutamide will be evaluated.

Inclusion Criteria:

- Pathologically confirmed adenocarcinoma of the prostate. Treatment-emergent small-cell
neuroendocrine prostate cancer (t-SCNC) on screening biopsy may be eligible for cohort
5

- Metastatic disease as documented by technetium-99m (99mTc) bone scan or metastatic
lesions by computed tomography (CT) or magnetic resonance imaging (MRI) scans
(visceral or lymph node disease). CT-portion of positron emission tomography (PET)/CT
scan may be used for eligibility. If lymph node metastasis is the only evidence of
metastatic disease, it must be greater than (>=) 1.0 centimeter (cm) in the short axis
and above the level of the iliac bifurcation

- Progressed while on therapy with abiraterone acetate plus prednisone/prednisolone
(AA-P), enzalutamide or apalutamide for metastatic castration-resistant prostate
cancer (mCRPC). No washout is required and no additional therapy may have been
administered between discontinuation of AR-targeted the agent and study treatment.
Participants will be assigned to cohorts based on the results of the biomarker panel.
Cohort 1: Biomarker-negative participants with adenocarcinoma (and not t-SCNC) who
progressed on abiraterone acetate plus prednisone/prednisolone (AA-P); Cohort 2:
Biomarker-negative participants with adenocarcinoma (and not t-SCNC) who progressed on
apalutamide or enzalutamide; Cohort 3: Biomarker-positive participants who progressed
on AA-P; Cohort 4: Biomarker-positive participants who progressed on apalutamide or
enzalutamide; Cohort 5: Biomarker-negative participants with t-SCNC who progressed on
treatment with AA-P, apalutamide or enzalutamide

- Surgical or medical castration, with testosterone levels of less than (<)50 nanogram
per deciliter (ng/dL). If the participant is being treated with gonadotropin-releasing
hormone (GnRH) analogs (participant who has not undergone bilateral orchiectomy), this
therapy must have been initiated at least 4 weeks prior to first dose of study drug
and must be continued throughout the study

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

Exclusion Criteria:

- Initial diagnosis of primary prostatic neuroendocrine or small cell carcinoma

- Brain metastases

- Prior treatment with an anti-programmed cell death receptor-1 (PD-1), anti-programmed
cell death ligand 1 (PD-L1), or anti-cytotoxic T-lymphocyte antigen 4 (CTLA-4)
antibody

- Prior chemotherapy, except for docetaxel for hormone-sensitive prostate cancer (HSPC)

- Prior therapy with poly adenosine diphosphate (ADP)-ribose polymerase (PARP)
inhibitors