Darolutamide in Addition to ADT Versus ADT in Metastatic Hormone-sensitive Prostate Cancer

Inclusion Criteria:

• Histologically or cytologically confirmed adenocarcinoma of prostate

• Metastatic disease

• Started ADT (LHRH agonist/antagonist or orchiectomy) with or without firstgeneration anti-androgen, but not earlier than 12 weeks before randomization

• Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0, 1 or 2

• Adequate bone marrow, liver and renal function

Exclusion Criteria:

• Prior treatment with: LHRH agonist/antagonists except neoadjuvant and /or adjuvanttherapy; Second-generation androgen receptor (AR) inhibitors such as enzalutamide,darolutamide, apalutamide or other investigational AR inhibitors; Cytochrome P17enzyme inhibitor such as abiraterone acetate or oral ketoconazole as anti-cancertreatment for prostate cancer; Chemotherapy including docetaxel or immunotherapy forprostate cancer; Use of systemic corticosteroid with dose greater than theequivalent 10 mg of prednisone/day within 28 days prior to randomization;Radiopharmaceuticals; Any other anti-cancer treatment for prostate cancer, excludinglocal therapies and ADT.

• Treatment with radiotherapy within 2 weeks before randomization

• Contraindication to iodinated CT and gadolinium chelate MRI intravenous contrastagent(s)

• Had any of the following within 6 months before randomization: stroke, myocardialinfarction, severe/unstable angina pectoris, coronary/peripheral artery bypassgraft, congestive heart failure (New York Heart Association Class III or IV)

• Uncontrolled hypertension as indicated by a resting systolic BP ≥ 160 mmHg ordiastolic BP ≥ 100 mmHg despite medical management

• A gastrointestinal (GI) disorder or procedure which is expected to interferesignificantly with absorption of study drug

• Any prior malignancy (other than adequately treated basal cell or squamous cell skincancer, superficial bladder cancer, or any other cancer in situ currently incomplete remission) within 5 years prior to randomization

• Inability to swallow oral medications