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

Key Inclusion Criteria:

• ECOG performance status:

1. Post-taxane population only: 0 to 2.

2. Pre-taxane population only: 0 to 1.

• Participants must have a previous histological, pathological, and/or cytologicalconfirmation of prostate cancer.

• Part 1/2/3 only; Participants must have a positive 68Ga-PSMA-11 PET/CT scan, asdetermined by the sponsor's central reader, before the enrollment to 177Lu-PSMA-617treatment period.

• Participants must have a positive 68Ga-PSMA-11 PET/CT scan, as determined by thelocal 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 (forexample enzalutamide, abiraterone, apalutamide, or darolutamide, etc.) in either thehormone-sensitive/castrate-resistant or non-metastatic/metastatic prostate cancersetting.

• Pre-taxane population only: Participants must have progressed only once on priorsecond generation ARDT (abiraterone, enzalutamide, darolutamide, or apalutamide) andbe a candidate for change in ARDT as assessed by the treating physician.

1. first generation androgen receptor inhibitor therapy (e.g. bicalutamide) isallowed but not considered as prior ARDT therapy

2. second generation ARDT must be the most recent therapy received.

• Post-taxane population only: Participants must have been previously treated with atleast 1, but no more than 2 prior taxane regimens. A taxane regimen is defined as aminimum exposure of 2 cycles of a taxane. If a participant has received only 1taxane regimen, the participant is eligible if : a. The participant's physician deems him unsuitable to receive a second taxaneregimen (e.g., frailty assessed by geriatric or health status evaluation orintolerance, etc.).

• Participants must have progressive mCRPC. Documented progressive mCRPC will be basedon at least 1 of the following criteria:

1. Serum PSA progression defined as 2 consecutive increases in PSA over a previousreference value measured at least 1 week prior. 1.0 ng/mL is the minimalstarting value if confirmed rise in PSA is the only indication of progression.

2. 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.

3. Progression of bone disease: two new lesions; only positivity on the bone scandefines metastatic disease to bone (PCWG3 criteria, Scher et al 2016).

• Part 1/2/3 only; Participants must have at least one measurable lesion perPCWG3-modified RECIST v1.1 on CT or MRI.

Key Exclusion Criteria:

• Previous treatment with any of the following within 6 months of the enrollment:Strontium-89, Samarium-153, Rhenium-186, Rhenium-188, Radium-223, hemi-bodyirradiation. 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 notincluded) within 28 days prior to day of the enrollment.

• Pre-taxane population: Prior treatment with PARP inhibitor, cytotoxic chemotherapyfor castration resistant or castrate sensitive prostate cancer (e.g., taxanes,platinum, estramustine, vincristine, methotrexate, etc.), immunotherapy orbiological therapy [including monoclonal antibodies]) [Note: Taxane exposure (maximum 6 cycles) in the adjuvant or neoadjuvant setting is allowed if 12 monthshave elapsed since completion of this adjuvant or neoadjuvant therapy]

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

• Concurrent cytotoxic chemotherapy, immunotherapy, radioligand therapy, PARPinhibitors, 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 notreceiving corticosteroids for the purposes of maintaining neurologic integrity.

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