An International Prospective Open-label, Randomized, Phase III Study Comparing 177Lu-PSMA-617 in Combination With SoC, Versus SoC Alone, in Adult Male Patients With mHSPC

Participants eligible for inclusion in this study must meet all of the following criteria:

Signed informed consent must be obtained prior to participation in the studyPatients must be adults ≥18 years of age Patients must have an ECOG performance status of 0 to 2 Patients must have a life expectancy >9 months as determined by the study investigator Patients must have metastatic prostate cancer with histologically or cytologically confirmed adenocarcinoma (current or prior biopsy of the prostate and/or metastatic site) Patients must have evidence of PSMA-positive disease as seen on a 68Ga-PSMA-11 PET/CT scan, and eligible as determined by the sponsor's central reader

Patients must have at least one documented metastatic bone and/or soft tissue/visceral lesion documented in the following manners within 28 days prior randomization:

Metastatic disease to the bone (in any distribution) visible on 99Tc-MDP bone scintigraphy on either pre-ADT scans or baseline scans AND/ORLymph node metastases of any size or distribution. If lymph nodes are the only site of metastasis, then at least one must be at least 1.5 cm in short axis AND outside of the pelvis AND/OR Visceral metastases of any size or distribution. If a participant has a history of visceral metastases at any time prior to randomization, he should be coded as having visceral metastases at baseline (i.e., patients with visceral metastases prior to ADT that disappear at baseline will be counted as having visceral metastases and would therefore have high volume disease for stratification purposes).

Patients must have adequate organ function:

Bone marrow reserve ANC ≥1.5 x 109/L Platelets ≥100 x 109/L Hemoglobin ≥9 g/dLHepatic Total bilirubin ≤2 x the institutional upper limit of normal (ULN). For patients with known Gilbert's Syndrome ≤3 x ULN is permitted Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≤3.0 x ULN OR ≤5.0 x ULN for patients with liver metastases Renal eGFR ≥ 50 mL/min/1.73m2 using the Modification of Diet in Renal Disease (MDRD) equation Albumin ≥2.5 g/dL Human immunodeficiency virus (HIV)-infected patients who are healthy and have a low risk of acquired immune deficiency syndrome (AIDS)-related outcomes can participate in this trial Patients must be:

Treatment naïve OR minimally treated with:

Up to 45 days of luteinizing hormone-releasing hormone (LHRH) agonist /antagonists or bilateral orchiectomy with or without first generation anti-androgen (e.g. bicalutamide, flutamide) for metastatic prostate cancer is allowed prior to ICF signature. If given, first generation anti-androgen must be discontinued prior to start of study therapy or after 45 days whatever happens first.If received, prior LHRH agonist/antagonist with or without first generation anti-androgen use in the adjuvant/neo-adjuvant setting must have been discontinued > 12 months prior to ICF signature AND must not have exceeded 24 months of therapy AND must not have shown disease progression within 12 months of completing adjuvant/neo-adjuvant therapy. Up to 45 days of CYP17 inhibitor or ARDT exposure for metastatic prostate cancer is allowed prior to ICF signature. No CYP17 inhibitor or ARDT exposure for earlier stages of prostate cancer is allowed.