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

Prior treatment

• Patient has received any other investigational therapeutic agents within 4 weeks or 5 half-lives (whichever is shorter) of starting the study treatment
• Patient has any concurrent severe and/or uncontrolled medical conditions that could increase the patient's risk for toxicity while on the study or that could confound discrimination between disease- and study treatment-related toxicities
• Criteria specific for patients with mCRPC:
  • Patient has received any PSMA-directed radioligand therapy (e.g., Lu-177-PSMA, Lu-177-PNT2002, Ac-225-J591)
  • 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
• Criteria specific for patients with OmHSPC:
  • Patient has received any systemic anti-cancer therapy for prostate cancer with the exception of (neo)adjuvant ADT for management of localized disease
  • Presence of any liver metastases
  • Known presence of central nervous system metastases

Other

• Evidence of ongoing and untreated urinary tract obstruction
• Existing Grade 1 dry mouth (xerostomia) or symptomatic Grade 1 dry eye (xerophthalmia) for any reason

• Histological, pathological, and/or cytological confirmation of adenocarcinoma of the prostate
• ECOG performance status 0 to 1
• Criteria specific for patients with mCRPC:
  • Previously received an androgen receptor pathway inhibitor (ARPI) and taxane-based chemotherapy (unless ineligible or refused taxane). Received a maximum of 3 prior systemic therapy regimens in the mCRPC setting
  • Progressive mCRPC at the time of consent based on at least 1 of the following criteria being met in the context of castrate levels of testosterone:
  • PSA progression defined as rising PSA values at a minimum of 1-week intervals, with the last result being at least 1.0 ng/mL
  • Soft-tissue progression defined as an increase ≥20% in the sum of the diameter (SOD) (short axis for nodal lesions and long axis for non-nodal lesions) of all target lesions based on the smallest SOD since treatment started or the appearance of one or more new lesions
  • Progression of bone disease defined as the appearance of two or more new lesions by bone scan
  • At least one PSMA-PET positive lesion for prostate cancer
  • Castrate circulating testosterone levels (\<1.74 nmol/L or \<50 ng/dL)
• Criteria specific for patients with OmHSPC:
  • 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
  • 1- 5 PSMA-PET positive lesions identified outside the prostate bed or remaining gland.