Title
A Phase 2, Open-label, Multi-cohort Study to Assess the Efficacy and Safety of ASP5541 in Participants with Advanced Prostate Cancer

Description
Hormone therapy, or androgen deprivation therapy (ADT) is a standard way to treat prostate cancer. It works by reducing the amount of the main male sex hormone, testosterone in the body. Androgen receptor pathway inhibitors (ARPIs) are another type of hormone therapy. They either slow down how much testosterone is made or block testosterone from reaching the prostate cancer cells. Abiraterone acetate (AA) is an ARPI that is used to treat advanced prostate cancer. This type of treatment is usually given as a tablet with a steroid called prednisone/prednisolone to manage any medical problems from the hormone therapy. ASP5541 is a different form of AA. It is given as an injection into the muscle. In this study, ASP5541 will be given to men with advanced prostate cancer, both with and without prednisone/prednisolone. This study will check the safety of ASP5541 and compare how well ASP5541 works in men with advanced prostate cancer compared to AA.

The main aims of the study are to check how well ASP5541 with prednisone/prednisolone works compared to AA with prednisone/prednisolone in men with advanced prostate cancer who haven't previously been treated with an ARPI, to check safety of ASP5541 given by itself in men with advanced prostate cancer that haven't previously been treated with an ARPI, to check how well ASP5541 given by itself works compared to AA with prednisone/prednisolone in men with advanced prostate cancer that haven't previously been treated with an ARPI, and to check safety of ASP5541 with prednisone/prednisolone in Japanese men with advanced prostate cancer.

Adult men with a certain type of advanced prostate cancer can take part. Their cancer has spread to other parts of the body (metastatic). The different types are: Metastatic hormone-sensitive prostate cancer (mHSPC). Prostate cancer that needs testosterone to grow. Metastatic castration-resistant prostate cancer (mCRPC). Prostate cancer that continues to grow even when testosterone levels are low

Objective
Primary Objectives
- To evaluate the efficacy of ASP5541 + pred compared with AA + pred in ARPI-naïve mCRPC participants (Cohort 1)
- To evaluate the safety of ASP5541 without steroids (Cohort 2 safety run-in) in ARPI-naïve mHSPC participants
- To evaluate the efficacy of ASP5541 without steroids compared with AA + pred in ARPI-naïve mHSPC participants (Cohort 2)

Secondary Objectives
- To further evaluate the efficacy of ASP5541 with and without pred compared with AA + pred
- To evaluate the safety of ASP5541 with and without pred compared with AA + pred
- To evaluate the pharmacodynamic profile of ASP5541 with and without pred compared with AA + pred
- To evaluate pain progression following ASP5541 with and without pred compared with AA + pred

Treatment In this study there will be 3 treatment groups. In Group 1 men with mCRPC who haven't previously been treated with an ARPI will either be given ASP5541 and prednisone/prednisolone or AA and prednisone/prednisolone. In Group 2 men with mHSPC who haven't previously been treated with an ARPI will either be given ASP5541 by itself or be given AA with prednisone/prednisolone. In Group 3 Japanese men with mCRPC or mHSPC who may or may not have previously been treated with an ARPI will be given ASP5541 with prednisone.

Key Eligibility Inclusion Criteria:

-Participant is diagnosed with histologically or cytologically confirmed adenocarcinoma of the prostate without neuroendocrine differentiation or small cell features.
-Participant has ECOG performance status of 0 or 1, or ECOG performance status of 2 if due to bone pain.
-Participant with mHSPC must have an estimated life expectancy of ≥ 12 months or > 6 months if participant has mCRPC.
-Participant is able to understand and comply with all study requirements and procedures, including completion of PRO questionnaires.
-Male participant must agree to use defined forms of contraception with female partner(s) of childbearing potential (including breastfeeding partner) throughout the treatment period and for 7 months after final ASP5541 or for 3 months after AA study intervention administration.
-Male participant must agree to remain abstinent or use a condom with pregnant partner(s) for the duration of the pregnancy throughout the investigational period and for 7 months after final ASP5541 or for 3 months after AA study intervention administration.
-Male participant must not donate sperm during the treatment period and for 7 months after final ASP5541 or for 3 months after AA study intervention administration.
-Participant has adequate ventrogluteal muscle mass for an intramuscular injection.
-Participant agrees not to participate in another interventional study while receiving ASP5541 in the present study.
-Participant should have normal serum potassium (within the local laboratory normal range) at screening without supplementation.

Applicable Disease Sites
Prostate

Participating Institutions
UW Health Eastpark Medical Center; UW Health University Hospital