Study of 177Lu-PSMA-617 In Metastatic Castrate-Resistant Prostate Cancer

Inclusion Criteria:

1. Patients must have the ability to understand and sign an approved informed consentform (ICF).

2. Patients must have the ability to understand and comply with all protocolrequirements.

3. Patients must be >= 18 years of age.

4. Patients must have an Eastern Cooperative Oncology Group (ECOG) performance statusof 0 to 2.

5. Patients must have a life expectancy >6 months.

6. Patients must have histological, pathological, and/or cytological confirmation ofprostate cancer.

7. Patients must be 68Ga-PSMA-11 Positron Emission Tomography (PET)/Computed Tomography (CT) scan positive, and eligible as determined by the sponsor's central reader.

8. Patients must have a castrate level of serum/plasma testosterone (<50 ng/dL or <1.7nmol/L).

9. Patients must have received at least one NAAD (such as enzalutamide and/orabiraterone).

10. Patients must have been previously treated with at least 1, but no more than 2previous taxane regimens. A taxane regimen is defined as a minimum exposure of 2cycles of a taxane. If a patient has received only 1 taxane regimen, the patient iseligible if: a. The patient's physician deems him unsuitable to receive a secondtaxane regimen (e.g. frailty assessed by geriatric or health status evaluation,intolerance, etc.).

11. Patients must have progressive mCRPC. Documented progressive mCRPC will be based onat least 1 of the following criteria:

12. Serum/plasma PSA progression defined as 2 consecutive increases in PSA over aprevious reference value measured at least 1 week prior. The minimal startvalue is 2.0 ng/mL.

13. Soft-tissue progression defined as an increase >= 20% in the sum of thediameter (SOD) (short axis for nodal lesions and long axis for non-nodallesions) of all target lesions based on the smallest SOD since treatmentstarted or the appearance of one or more new lesions.

14. Progression of bone disease: evaluable disease or new bone lesions(s) by bonescan (2+2 PCWG3 criteria, Scher et al 2016).

15. Patients must have >= 1 metastatic lesion that is present on baseline CT, MRI, orbone scan imaging obtained =< 28 days prior to beginning study therapy.

16. Patients must have recovered to =< Grade 2 from all clinically significanttoxicities related to prior therapies (i.e. prior chemotherapy, radiation,immunotherapy, etc.).

17. Patients must have adequate organ function: a. Bone marrow reserve:

• White blood cell (WBC) count >= 2.5 x 10^9/L (2.5 x 10^9/L is equivalent to 2.5x 10^3/μL and 2.5 x K/μL and 2.5 x 10^3/cumm and 2500/μL) OR absoluteneutrophil count (ANC) >= 1.5 x 10^9/L (1.5 x 10^9/L is equivalent to 1.5 x 10^3/μL and 1.5 x K/μL and 1.5 x 10^3/cumm and 1500/μL)

• Platelets >= 100 x 10^9/L (100 x 10^9/L is equivalent to 100 x 10^3/μL and 100x K/μL and 100 x 10^3/cumm and 100,000/μL)

• Hemoglobin >= 9 g/dL (9 g/dL is equivalent to 90 g/L and 5.59 mmol/L) b.Hepatic:

• Total bilirubin =< 1.5 x the institutional upper limit of normal (ULN). Forpatients with known Gilbert's Syndrome =< 3 x ULN is permitted

• Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) =< 3.0 x ULNOR =< 5.0 x ULN for patients with liver metastases c. Renal:

• Serum/plasma creatinine =< 1.5 x ULN or creatinine clearance >= 50 mL/min

15. Albumin >3.0 g/dL (3.0 g/dL is equivalent to 30 g/L) [Inclusion #16 has beenremoved]

16. HIV-infected patients who are healthy and have a low risk of AIDS-related outcomesare included in this trial.

17. For patients who have partners of childbearing potential: Partner and/or patientmust use a method of birth control with adequate barrier protection, deemedacceptable by the principle investigator during the study and for 6 months afterlast study drug administration.

18. The best standard of care/ best supportive care options planned for this patient:

19. Are allowed by the protocol

20. Have been agreed to by the treating investigator and patient

21. Allow for the management of the patient without 177Lu-PSMA-617

Exclusion Criteria:

1. Previous treatment with any of the following within 6 months of randomization:Strontium-89, Samarium-153, Rhenium-186, Rhenium-188, Radium-223, hemi-bodyirradiation. Previous PSMA-targeted radioligand therapy is not allowed.

2. Any systemic anti-cancer therapy (e.g. chemotherapy, immunotherapy or biologicaltherapy [including monoclonal antibodies]) within 28 days prior to day ofrandomization.

3. Any investigational agents within 28 days prior to day of randomization.

4. Known hypersensitivity to the components of the study therapy or its analogs.

5. Other concurrent cytotoxic chemotherapy, immunotherapy, radioligand therapy, orinvestigational therapy.

6. Transfusion for the sole purpose of making a subject eligible for study inclusion.

7. Patients with a history of Central Nervous System (CNS) metastases must havereceived therapy (surgery, radiotherapy, gamma knife) and be neurologically stable,asymptomatic, and not receiving corticosteroids for the purposes of maintainingneurologic integrity. Patients with epidural disease, canal disease and prior cordinvolvement are eligible if those areas have been treated, are stable, and notneurologically impaired. For patients with parenchymal CNS metastasis (or a historyof CNS metastasis), baseline and subsequent radiological imaging must includeevaluation of the brain (MRI preferred or CT with contrast).

8. A superscan as seen in the baseline bone scan.

9. Symptomatic cord compression, or clinical or radiologic findings indicative ofimpending cord compression.

10. Concurrent serious (as determined by the Principal Investigator) medical conditions,including, but not limited to, New York Heart Association class III or IV congestiveheart failure, history of congenital prolonged QT syndrome, uncontrolled infection,known active hepatitis B or C, or other significant co-morbid conditions that in theopinion of the investigator would impair study participation or cooperation.

11. Diagnosed with other malignancies that are expected to alter life expectancy or mayinterfere with disease assessment. However, patients with a prior history ofmalignancy that has been adequately treated and who have been disease free for morethan 3 years are eligible, as are patients with adequately treated non-melanoma skincancer, superficial bladder cancer.