A Study of Adding Apalutamide to Radiotherapy and LHRH Agonist in High-Risk Patients With Hormone-Sensitive Prostate Cancer

Inclusion Criteria:

• Histologically confirmed adenocarcinoma of the prostate

• Previously treated with radical prostatectomy with or without lymph node dissectionand either: a) for biochemical recurrence after radical prostatectomy (RP): anypost-operative prostate-specific antigen (PSA) measurement of less than (<) 0.1nanogram/milliliter (ng/mL) within 12 months after RP and without any PSA greaterthan and equal to (>=) 0.1 ng/mL within the 4 to 8-week period after RP or b) forpersistent PSA after RP: PSA >=0.1 ng/mL within the 4 to 8-week period after RP,confirmed by additional measurement at least 3 weeks later

• Be able to swallow whole the study drug tablets or follow the instructions foradmixing with apple sauce

• Results of the Prostate specific membrane antigen-positron emission tomography (PSMA-PET) at screening as determined by blinded independent, central review (BICR),must be: PSMA-PET-negative for any prostate cancer lesions (that is, noloco-regional lesion and no distant lesions); or PSMA-PET-positive for at least oneloco-regional (pelvic) lesion without distant extra-pelvic lesion; or PSMA PET-positive for at least one loco--regional (pelvic) lesion with extra-pelviclesion(s).

• High risk of developing metastasis defined as; a) for biochemical recurrence afterRP: pathological Gleason score greater than or equal to (>=) 8 evaluated fromprostate tissue specimen at radical prostatectomy, or prostate-specific antigendoubling time (PSADT) less than or equal to (<=) 12 months at the time of screening;b) for persistent PSA after RP: pathological Gleason score >=8, evaluated fromprostate tissue specimen at radical prostatectomy

• Participants with evidence of distant metastasis on screening PSMA-PET scan musthave no evidence of prostate cancer metastases on screening CT/MRI of thechest/abdomen/pelvis, Technetium 99m [99mTc] whole-body bone scan. Participants witha single bone lesion on 99mTc whole-body bone scan should have confirmatory imagingby CT or MRI; if the confirmatory scan confirms the bone lesion, the participantshould be excluded from the study. Conventional images (99mTc-bone scan and CT/MRI)from the screening will be evaluated locally before randomization

• Eastern Cooperative Oncology Group Performance Status Grade 0 or 1

Exclusion Criteria:

• History of pelvic radiation for malignancy

• Previous treatment with androgen deprivation therapy (ADT) for prostate cancer

• Previously treated for biochemical recurrence (BCR) or persistent PSA after RP (previous surgical treatment of one or more loco-regional lesions is allowed)

• Prior treatment with a CYP17 inhibitor (example, oral ketoconazole, orteronel,abiraterone acetate, galeterone) or any androgen receptor (AR) antagonist includingbicalutamide, flutamide, nilutamide, apalutamide, enzalutamide or darolutamide andany other medications that may lower androgen levels (estrogens, progestins,aminoglutethimide, etc.), including bilateral orchiectomy

• Known or suspected contraindications or hypersensitivity to apalutamide, LuteinizingHormone-Releasing Hormone (LHRH) agonist or any of the components of theformulations

• Prior chemotherapy for prostate cancer

• Any evidence of prostate cancer metastasis on computed tomography/magnetic resonanceimaging (CT/MRI) of the chest/abdomen/pelvis or 99mTc whole-body bone scan, at anytime prior to screening