[Ac-225]-PSMA-62 Trial in Oligometastatic Hormone Sensitive and Metastatic Castration Resistant Prostate Cancer

Inclusion Criteria:

1. Histological, pathological, and/or cytological confirmation of adenocarcinoma of theprostate

2. ECOG performance status 0 to 1

3. Criteria specific for patients with mCRPC:

4. Previously received an androgen receptor pathway inhibitor (ARPI) andtaxane-based chemotherapy (unless ineligible or refused taxane). Received amaximum of 3 prior systemic therapy regimens in the mCRPC setting

5. Progressive mCRPC at the time of consent based on at least 1 of the followingcriteria being met in the context of castrate levels of testosterone:

• PSA progression defined as rising PSA values at a minimum of 1-weekintervals, with the last result being at least 1.0 ng/mL
• 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
• Progression of bone disease defined as the appearance of two or more newlesions by bone scan

3. At least one PSMA-PET positive lesion for prostate cancer

4. Castrate circulating testosterone levels (<1.74 nmol/L or <50 ng/dL)

5. Criteria specific for patients with OmHSPC:

6. PSA recurrence after radical prostatectomy (RP) or definitive radiation therapy (RT), with or without adjuvant/salvage local therapy (radiation or surgery),with or without (neo)adjuvant ADT

• PSA ≥ 0.2ng/mL for patients with prior RP +/- RT, or
• PSA of ≥ 2 ng/mL above nadir for patients with only prior RT

2. 1- 5 PSMA-PET positive lesions identified outside the prostate bed or remaininggland.

Exclusion Criteria:

1. Patient has received any other investigational therapeutic agents within 4 weeks or 5 half-lives (whichever is shorter) of starting the study treatment

2. Evidence of ongoing and untreated urinary tract obstruction

3. Existing Grade 1 dry mouth (xerostomia) or symptomatic Grade 1 dry eye (xerophthalmia) for any reason

4. Patient has any concurrent severe and/or uncontrolled medical conditions that couldincrease the patient's risk for toxicity while on the study or that could confounddiscrimination between disease- and study treatment-related toxicities

5. Criteria specific for patients with mCRPC:

6. Patient has received any PSMA-directed radioligand therapy (e.g., Lu-177-PSMA,Lu-177-PNT2002, Ac-225-J591)

7. Patient has received any therapeutic systemic radionuclides (e.g., radium-223,rhenium-186, strontium-89), or non-PSMA-directed therapeutic radioligands (e.g., Lu-177-Dotatate) within 5 half-lives of starting the study treatment

8. Criteria specific for patients with OmHSPC:

9. Patient has received any systemic anti-cancer therapy for prostate cancer withthe exception of (neo)adjuvant ADT for management of localized disease

10. Presence of any liver metastases

11. Known presence of central nervous system metastases