A Prospective, Open Label, Multicenter, Single Arm, Phase 2 Study of 177Lu-PSMA-617 in the Treatment of Participants With Progressive PSMA- Positive Metastatic Castration-resistant Prostate Cancer (mCRPC) in Japan
The purpose of this study is to assess the efficacy, tolerability, safety, pharmacokinetic (PK) and dosimetry of 177Lu-PSMA-617, in participants with progressive prostate-specific membrane antigen (PSMA)-positive metastatic castration-resistant prostate cancer (mCRPC) in Japan. Furthermore, the safety, PK and dosimetry of 68Ga-PSMA-11 (PSMA imaging agent) are assessed in the same study. Another purpose of this study is to provide humanistic perspective access to study treatment (68Ga-PSMA-11 and 177Lu-PSMA-617) for the eligible patients with PSMA-positive mCRPC until marketed products are available in Japan. Furthermore, if data availability PK and dose rate of 177 Lu-PSMA-617 will be evaluated to refine discharge criteria in Japan. After obtaining manufacturing and marketing approval in Japan, this clinical trial will continue as a post marketing trial.
• 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 :
• 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:
‣ 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.