A Trial Comparing Docetaxel 75 mg/m2 (3w) Versus Docetaxel 50 mg/m2 (2w) in Combination With Darolutamide + ADT in mHSPC Patients

Inclusion Criteria:

• Written informed consent

• Males ≥18 years of age

• Histologically or cytologically confirmed adenocarcinoma of prostate

• Investigator assessed metastatic disease documented either by a positive bone scan,or for soft tissue or visceral metastases, either by contrast-enhancedabdominal/pelvic/chest computed tomography (CT) or magnetic resonance imaging (MRI)scan assessed. Metastatic disease is defined as either malignant lesions in bonescan or soft tissue/visceral lesions according to Response Evaluation Criteria InSolid Tumors (RECIST) 1.1. Lymph nodes are measurable if the short axis diameter is ≥15 mm, soft tissue/visceral lesions are measurable if the long axis diameter is ≥10mm.

• Subjects with lymph node metastases only (either below the aortic bifurcation (N1)or above the aortic bifurcation (M1a)) will not be eligible for the study.

• Subjects must be candidates for ADT, docetaxel and darolutamide therapy perInvestigator's judgment

• Started ADT (LHRH agonist/antagonist or orchiectomy) with or without firstgeneration anti-androgen, but no longer than 12 weeks before randomization. Forsubjects receiving LHRH agonists, treatment in combination with a first generationanti-androgen for at least 4 weeks, prior to randomization is recommended. Firstgeneration anti-androgen has to be stopped prior to randomization.

• An Eastern Cooperative Oncology Group performance status of 0 or 1

• Blood counts at Screening: hemoglobin ≥9.0 g/dL, absolute neutrophil count ≥1.5x109/L, platelet count ≥100x109/L (subject must not have received any growthfactor within 4 weeks or a blood transfusion within 7 days of the hematologylaboratory sample obtained at Screening)

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

Sexually active male subjects must agree to use condoms as an effective barrier method and refrain from sperm donation, and/or their female partners of reproductive potential to use a method of effective birth control, during the treatment with darolutamide and for 3 months after the end of the treatment with darolutamide and 6 months after treatment with docetaxel.

Exclusion Criteria:

• Exclusion criteria

• Prior treatment with:

• LHRH agonist/antagonists started more than 12 weeks before randomizationSecond-generation androgen receptor (AR) inhibitors such as enzalutamide,apalutamide, darolutamide, other investigational AR inhibitors

• Cytochrome P 17 enzyme inhibitor such as abiraterone acetate or oral ketoconazole asantineoplastic treatment for prostate cancer

• Chemotherapy, immunotherapy, radium or other therapeutic radiopharmaceuticals forprostate cancer (e.g. Lutetium177-PSMA) prior to randomization

• Treatment with radiotherapy (external beam radiation therapy, brachytherapy) within 2 weeks before randomization

• Known hypersensitivity to any of the study drugs, study drug classes, or excipientsin the formulation of the study drugs

• Contraindication to both CT and MRI contrast agent

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

• Uncontrolled hypertension as indicated by a resting systolic blood pressure (BP) ≥160 mmHg or diastolic BP ≥100 mmHg despite medical management

• Had a prior malignancy. Adequately treated basal cell or squamous cell carcinoma ofskin or superficial bladder cancer that has not spread behind the connective tissuelayer (i.e., pTis, pTa, and pT1) is allowed, as well as any other cancer for whichtreatment has been completed ≥5 years before randomization and from which thesubject has been disease-free

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

• An active viral hepatitis, known human immunodeficiency virus infection withdetectable viral load, or chronic liver disease with a need for treatment

• Previous (within 28 days before the start of study drug or 5 half-lives of theinvestigational treatment of the previous study, whichever is longer) or concomitantparticipation in another clinical study with investigational medicinal product(s)

• Any other serious or unstable illness, or medical, social, or psychologicalcondition, that could jeopardize the safety of the subject and/or his/her compliancewith study procedures, or may interfere with the subject's participation in thestudy or evaluation of the study results

• Inability to swallow oral medications

• Previous assignment to treatment in this study