Efficacy and Safety Study of Darolutamide (ODM-201) in Men With High-risk Nonmetastatic Castration-resistant Prostate Cancer

Inclusion Criteria:

- Histologically or cytologically confirmed adenocarcinoma of prostate without
neuroendocrine differentiation or small cell features.

- Castration-resistant prostate cancer (CRPC) with castrate level of serum testosterone.

- Prostate-specific antigen doubling time of ≤ 10 months and PSA > 2ng/ml.

- Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.

- Blood counts at screening: haemoglobin ≥ 9.0 g/dl,absolute neutrophil count ≥ 1500/µl,
platelet count ≥ 100,000/µl.

- Screening values of serum alanine aminotransferase (ALT) and/or aspartate transaminase
(AST) ≤ 2.5 x upper limit of normal (ULN), total bilirubin ≤ 1.5 x ULN, creatinine ≤
2.0 x ULN.

- Sexually active patients, unless surgically sterile, must agree to use condoms as an
effective barrier method and refrain from sperm donation during the study treatment
and for 3 months after the end of the study treatment.

Exclusion Criteria:

- History of metastatic disease at any time or presence of detectable metastases.

- Acute toxicities of prior treatments and procedures not resolved to grade ≤ 1 or
baseline before randomisation.

- Prior treatment with: second generation androgen receptor (AR) inhibitors, other
investigational AR inhibitors, or CYP17 enzyme inhibitor.

- Use of estrogens or 5-α reductase inhibitors or AR inhibitors.

- Prior chemotherapy or immunotherapy for prostate cancer.

- Use of systemic corticosteroid.

- Radiation therapy within 12 weeks before randomisation.

- Severe or uncontrolled concurrent disease, infection or co-morbidity.

- Treatment with bisphosphonate or denosumab within 12 weeks before randomisation.

- Known hypersensitivity to the study treatment or any of its ingredients.

- Major surgery within 28 days before randomisation.

- Any of the following within 6 months before randomisation: stroke, myocardial
infarction, severe/unstable angina pectoris, coronary/peripheral artery bypass graft;
congestive heart failure New York Heart Association (NYHA) Class III or IV.

- Uncontrolled hypertension.

- Prior malignancy.

- Gastrointestinal disorder or procedure which expects to interfere significantly with
absorption of study treatment.

- Active viral hepatitis, active human immunodeficiency virus (HIV) or chronic liver
disease.

- Treatment with any investigational drug within 28 days before randomisation.

- Any condition that in the opinion of the investigator would impair the patients'
ability to comply with the study procedures.