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

Prior treatment

• Previous treatment with any of the following within 6 months of the enrollment: Strontium-89, Samarium-153, Rhenium-186, Rhenium-188, Radium-223, hemi-body irradiation. Previous PSMA-targeted therapy is not allowed.
• Post-taxane population: Any systemic anti-cancer therapy (e.g. chemotherapy, immunotherapy or biological therapy \[including monoclonal antibodies\], ARDT is not included) within 28 days prior to day of the enrollment.
• Pre-taxane population: Prior treatment with PARP inhibitor, cytotoxic chemotherapy for castration resistant or castrate sensitive prostate cancer (e.g., taxanes, platinum, estramustine, vincristine, methotrexate, etc.), immunotherapy or biological therapy \[including monoclonal antibodies\]) \[Note: Taxane exposure (maximum 6 cycles) in the adjuvant or neoadjuvant setting is allowed if 12 months have elapsed since completion of this adjuvant or neoadjuvant therapy\]
• Concurrent cytotoxic chemotherapy, immunotherapy, radioligand therapy, PARP inhibitors, biological, AKT inhibitors or investigational therapy.
• Participants with a history of CNS metastases must have received therapy (surgery, radiotherapy, gamma knife) and be neurologically stable, asymptomatic, and not receiving corticosteroids for the purposes of maintaining neurologic integrity.

Other illness

• Known hypersensitivity to the components of 177Lu-PSMA-617, 68Ga-PSMA-11 or excipients or to drugs of similar classes.

Other

• Symptomatic cord compression, or clinical or radiologic findings indicative of impending cord compression.

• ECOG performance status:
  • Post-taxane population only: 0 to 2.
  • Pre-taxane population only: 0 to 1.
• Participants must have a previous histological, pathological, and/or cytological confirmation of prostate cancer.
• Part 1/2/3 only; Participants must have a positive 68Ga-PSMA-11 PET/CT scan, as determined by the sponsor's central reader, before the enrollment to 177Lu-PSMA-617 treatment period.
• Participants must have a positive 68Ga-PSMA-11 PET/CT scan, as determined by the local investigator, before the enrollment to 177Lu-PSMA-617 treatment period.
• Participants must have a castrate level of serum/plasma testosterone (\<50 ng/dL or \<1.7 nmol/L).
• Post-taxane population only: Participants must have received at least one ARDT (for example enzalutamide, abiraterone, apalutamide, or darolutamide, etc.) in either the hormone-sensitive/castrate-resistant or non-metastatic/metastatic prostate cancer setting.
• Pre-taxane population only: Participants must have progressed only once on prior second generation ARDT (abiraterone, enzalutamide, darolutamide, or apalutamide) and be a candidate for change in ARDT as assessed by the treating physician.
  • first generation androgen receptor inhibitor therapy (e.g. bicalutamide) is allowed but not considered as prior ARDT therapy
  • second generation ARDT must be the most recent therapy received.
• Post-taxane population only: Participants must have been previously treated with at least 1, but no more than 2 prior taxane regimens. A taxane regimen is defined as a minimum exposure of 2 cycles of a taxane. If a participant has received only 1 taxane regimen, the participant is eligible if :
  • The participant's physician deems him unsuitable to receive a second taxane regimen (e.g., frailty assessed by geriatric or health status evaluation or intolerance, etc.).
• Participants must have progressive mCRPC. Documented progressive mCRPC will be based on at least 1 of the following criteria:
  • Serum PSA progression defined as 2 consecutive increases in PSA over a previous reference value measured at least 1 week prior. 1.0 ng/mL is the minimal starting value if confirmed rise in PSA is the only indication of progression.
  • 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: two new lesions; only positivity on the bone scan defines metastatic disease to bone (PCWG3 criteria, Scher et al 2016).
• Part 1/2/3 only; Participants must have at least one measurable lesion per PCWG3-modified RECIST v1.1 on CT or MRI.