Study to Evaluate the Safety, Tolerability,Pharmacokinetics, and Antitumor Activity of a Thorium-227 Labeled Antibody-chelator Conjugate Alone and in Combination With Darolutamide, in Patients With Metastatic Castration Resistant Prostate Cancer

Exclusion Criteria

• •Diffuse bone or bone-marrow involvement (i.e. "superscan").
• •Spinal cord compression or known brain metastases.
• •Known incompatibility to CT/MRI, bone scan or uncontrolled pain, which results in patient's lack of compliance with the CT/MRI and bone scan required for PCWG3 tumor assessment.
• •Clinically significant heart disease, as evidenced by myocardial infarction, arterial thrombotic events in the past 6 months, severe or unstable angina, or uncontrolled cardiovascular history.
• •Patients known to be affected by genetic defects linked to radiation Hypersensitivity.
• •Known history of myelodysplastic syndrome (MDS) / leukemia or with features suggestive of MDS/AML at any time point.
• •Concurrent or active cancer within the last 2 years with a distinct primary site or histology from the cancer being evaluated in this study, with the exception of cancer types with less than 30% likelihood of recurrence.
• •Known allergies, hypersensitivity, or intolerance to the study drug including excipients, or to contrast agents used in the diagnostic or exploratory imaging procedures required per protocol.
• •Any infection of National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 5.0 Grade ≥ 2.
• •Known human immunodeficiency virus (HIV) infection.
• •Patients who have an active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection requiring treatment.
• •Serious, non-healing wound, ulcer, or bone fracture.
• •Any systemic anti-neoplastic therapy (e.g. chemotherapy, immunotherapy or biological therapy \[including monoclonal antibodies\], PARP inhibitors) within at least 30 days prior to day of randomization (except for Luteinizing Hormone-releasing Hormone \[LHRH\] or Gonadotropin-releasing Hormone \[GnRH\]).
• •Previous high-dose chemotherapy, needing hemopoietic stem cell rescue, is prohibited.
• •Prior major surgery (excluding prostatic biopsies) must be at least 12 weeks prior to study entry.
• •Previous treatment with therapeutic PSMA-targeted agents.
• •Previous treatment with radium-223 dichloride or other radiopharmaceuticals, including but not limited to strontium-89 or samarium-153.
• •Prior definitive radiotherapy completed less than 6 weeks before start of the study drug administration
• •Inability to swallow oral medications
• •A gastrointestinal disorder or procedure which is expected to interfere significantly with absorption of darolutamide