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 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.

1. first generation androgen receptor inhibitor therapy (e.g. bicalutamide) is
allowed 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 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 :

a. 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:

1. 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.

2. 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.

3. 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.

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-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]

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

- 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.

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