A Phase 2 Study to Evaluate the Effects of ASP5541 in Participants With Prostate Cancer

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

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 abiraterone acetate. 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 abiraterone acetate.

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 the 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.
• To check the 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.

In this study there will be 3 treatment groups:

• In Group 1, men with mCRPC who haven't previously been treated with an androgen receptor pathway inhibitor will either be given ASP5541 and prednisone/prednisolone or be given abiraterone acetate and prednisone/prednisolone.
• In Group 2, men with mHSPC who haven't previously been treated with an androgen receptor pathway inhibitor will either be given ASP5541 by itself or be given abiraterone acetate with prednisone/prednisolone.
• In Group 3, Japanese men with mCRPC or mHSPC who may or may not have previously been treated with an androgen receptor pathway inhibitor will be given ASP5541 with prednisone/prednisolone.

ASP5541 will be given as an injection into a muscle every 12 weeks. Men with mCRPC will take prednisone/prednisolone twice daily and men with mHSPC will take prednisone/prednisolone once daily. Abiraterone acetate will be given as tablets to be taken once daily. All groups will also receive the standard of care treatment, such as androgen deprivation therapy.

The men in the study will visit their clinic regularly during and after treatment for health checks, including checking for any medical problems. Some men (Group 2) will check their blood pressure weekly at home. On some visits they will also have scans to check for any changes in their cancer. The number of visits and type of safety checks done at each visit will depend on the health of each person and when they completed their treatment.

Study Overview

• Status: Recruiting
• Conditions: Prostate Cancer; Metastatic Castration-Resistant Prostate Cancer; Metastatic Hormone Sensitive Prostate Cancer
• Intervention / Treatment: Drug: Prednisolone; Drug: Prednisone; Drug: ASP5541; Drug: abiraterone acetate; Drug: Adrenocorticotropic hormone

• Study Type: Interventional
• Enrollment (Estimated): 218
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Astellas Pharma Global Development, Inc.; Phone Number: 800-888-7704; Email: astellas.registration@astellas.com

Study Locations

• China
  • Huaian, China, 211731
    • Recruiting
    • Huai'an first people's hospital
  • Shanghai, China, 200127
    • Recruiting
    • Renji Hospital Shanghai Jiaotong Univ School of Medicine
  • Jiangsu
    • Yangzhou, Jiangsu, China, 225001
      • Recruiting
      • Subei People's Hospital
  • Tianjin Municipality
    • Tianjin, Tianjin Municipality, China, 300211
      • Recruiting
      • The Second Hospital of Tianjin Medical University
  • Zhejiang
    • Hangzhou, Zhejiang, China
      • Recruiting
      • The First Affiliated Hospital, Zhejiang University School of Medicine
• France
  • Lille, France
    • Recruiting
    • Site FR33008
  • Strasbourg, France
    • Recruiting
    • Site FR33004
• Germany
  • Heinsberg, Germany
    • Recruiting
    • Site DE49001
  • Baden-Wurttemberg
    • Nürtingen, Baden-Wurttemberg, Germany
      • Recruiting
      • Site DE49004
• Italy
  • Milan, Italy
    • Recruiting
    • Site IT39004
  • Milan, Italy
    • Recruiting
    • Site IT39006
  • Roma, Italy
    • Recruiting
    • Site IT39005
  • Trento, Italy
    • Recruiting
    • Site IT39003
• Japan
  • Fukuoka, Japan
    • Recruiting
    • Harasanshin Hospital
  • Osaka, Japan
    • Recruiting
    • Osaka International Cancer Institute
  • Chiba
    • Kashiwa, Chiba, Japan
      • Recruiting
      • National Cancer Center Hospital East
  • Shizuoka
    • Sunto-gun, Shizuoka, Japan
      • Recruiting
      • Shizuoka Cancer Center
  • Tokyo
    • Bunkyo-ku, Tokyo, Japan
      • Recruiting
      • Nippon Medical School Hospital
    • Koto, Tokyo, Japan
      • Recruiting
      • The Cancer Institute Hospital of JFCR
• Poland
  • Mysłowice, Poland
    • Recruiting
    • Site PL48005
  • Otwock, Poland
    • Recruiting
    • Site PL48008
• Puerto Rico
  • San Juan, Puerto Rico
    • Recruiting
    • PanOncology Trials
• South Korea
  • Gwangju, South Korea
    • Recruiting
    • Site KR82008
  • Seoul, South Korea
    • Recruiting
    • Site KR82002
  • Seoul, South Korea
    • Recruiting
    • Site KR82003
  • Seoul, South Korea
    • Recruiting
    • Site KR82004
  • Seoul, South Korea
    • Recruiting
    • Site KR82007
• Spain
  • Barcelona, Spain
    • Recruiting
    • Site ES34008
  • Madrid, Spain
    • Recruiting
    • Site ES34001
  • Santiago de Compostela, Spain
    • Recruiting
    • Site ES34003
  • Catalonia
    • Barcelona, Catalonia, Spain
      • Recruiting
      • Site ES34006
• Taiwan
  • Kaohsiung City, Taiwan
    • Recruiting
    • Site TW88603
  • Taipei, Taiwan
    • Recruiting
    • Site TW88602
• United Kingdom
  • London, United Kingdom
    • Recruiting
    • Site GB44003
• United States
  • Alabama
    • Huntsville, Alabama, United States, 35805
      • Recruiting
      • Clearview Cancer Institute
  • California
    • San Diego, California, United States, 92123
      • Recruiting
      • Sharp HealthCare - Sharp Memorial Hospital
  • Florida
    • Tampa, Florida, United States, 33612
      • Recruiting
      • H. Lee Moffitt Cancer Center
  • Illinois
    • Chicago Ridge, Illinois, United States, 60415
      • Recruiting
      • Associated Urological Specialists
    • Evanston, Illinois, United States, 60201
      • Recruiting
      • NorthShore University HealthSystem
  • Louisiana
    • New Orleans, Louisiana, United States, 70121
      • Recruiting
      • Ochsner Health - Ochsner Medical Center - New Orleans
  • New Mexico
    • Albuquerque, New Mexico, United States, 87109
      • Recruiting
      • New Mexico Oncology Hematology Consultants
  • Ohio
    • Cincinnati, Ohio, United States, 45212
      • Recruiting
      • Solaris Health - The Urology Group
  • South Carolina
    • Myrtle Beach, South Carolina, United States, 29572
      • Recruiting
      • Carolina Urologic Research Center
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Recruiting
      • Tennessee Oncology Nashville
  • Virginia
    • Charlottesville, Virginia, United States, 22908-07
      • Recruiting
      • University of Virginia Cancer Center
  • Wisconsin
    • Madison, Wisconsin, United States, 53792
      • Recruiting
      • UW Health Carbone Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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 must have an estimated life expectancy of ≥ 12 months with mHSPC or ≥ 6 months with mCRPC.
• Participant is able to understand and comply with all study requirements and procedures.
• Participant has been diagnosed with mCRPC or mHSPC documented by metastatic lesions on a bone scan, computed tomography (CT), magnetic resonance imaging (MRI) or prostate-specific membrane antigen positron emission tomography (PSMA-PET).
• Participant is receiving ongoing ADT with a gonadotropin-releasing hormone (GnRH) analogue or has a history of bilateral orchiectomy (i.e., surgical or medical castration). Participant with mHSPC must have started castration therapy (medical or surgical) at least 14 days prior to Cycle 1 Day 1 (C1D1).

Note: Participant who has not had a bilateral orchiectomy must have a plan to maintain effective GnRH analogue therapy for the duration of the study.

• If the participant has mCRPC, participant has evidence of disease progression defined as 1 or more of the following criteria at study entry:

  • Evidence of radiographic progression of disease prior to first dose and following the most recent prostate cancer treatment, defined as progressive disease on CT/MRI per Response Evaluation Criteria in Solid Tumours (RECIST) v1.1 or on a bone scan per PCWG3.
  • PSA progression defined as an increase in PSA of at least 25% and ≥ 1 ng/mL above the nadir, confirmed by a second value 1 week later, and with at least 1 of the measurements within 90 days prior to screening. PSA nadir is defined as the lowest PSA during or after the most recent treatment.
• If the participant has mCRPC, participant has a serum testosterone level < 1.73 nmol/L (< 50 ng/dL) at the Screening visit.
• Male participant must agree to use contraception with female partner(s) of childbearing potential (including breastfeeding partner) throughout the treatment period and for 7 months after final ASP5541 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 administration.
• Male participant must not donate sperm during the treatment period and for 7 months after final ASP5541 administration.
• 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.

Exclusion Criteria:

• Participant has any concurrent disease, infection or comorbid condition that interferes with the ability of the subject to participate in the study, which places the subject at undue risk or complicates the interpretation of data.
• Participant has known active central nervous system (CNS) metastases. Note: Participant with CNS metastases who has been treated with surgery and/or radiation therapy, who is off pharmacologic doses of glucocorticoids and who is neurologically stable is eligible.

• Participant has a known additional malignancy beyond prostate cancer that requires active treatment with the exception of any of the following:

  • Adequately treated basal cell carcinoma, squamous cell carcinoma of the skin, or in situ carcinoma of any type
  • Adequately treated Stage I cancer from which the participant is currently in remission and has been in remission for ≥ 2 years
  • Any other cancer from which the participant has been disease-free for ≥5 years

• Participant has clinically significant cardiac disease, defined as any of the following:

  • Clinically significant cardiac arrhythmias including bradyarrhythmia which are poorly controlled. Rate-controlled atrial fibrillation is permitted.
  • Congenital long QT syndrome.
  • QT interval corrected by Fridericia's formula (QTcF) ≥450 msec at Screening. If the QT interval corrected for heart rate intervals (QTc) is prolonged in a participant with a pacemaker or bundle branch block, the participant may be enrolled in the study if confirmed by the medical monitor.
  • History of clinically significant cardiac disease or congestive heart failure greater than New York Heart Association (NYHA) Class II or left ventricular ejection fraction measurement of < 50% at baseline.
  • Cohorts 1 and 3: Participant must not have unstable angina (symptoms at rest) or new-onset angina within the last 3 months or myocardial infarction within the past 6 months.
  • Cohort 2: Participants must not have symptomatic heart failure, unstable or new-onset angina or myocardial infarction within the past 12 months.
  • Cohorts 1 and 3: Uncontrolled hypertension, defined as systolic blood pressure > 160 mmHg or diastolic blood pressure > 100 mmHg that has been confirmed by 2 successive measurements despite optimal medical management.
  • Cohort 2: Uncontrolled hypertension, defined as systolic BP > 140 mmHg or diastolic BP > 90 mmHg that has been confirmed by 2 successive measurements despite optimal medical management. Participants may be receiving a maximum of 2 antihypertensives that were initiated at least 3 months prior to Cycle 1 Day 1.
  • Cohort 1 and 3: Arterial or venous thrombotic or embolic events such as cerebrovascular accident (including transient ischemic attacks), deep vein thrombosis, or pulmonary embolism within the 3 months before start of study medication (except for adequately treated catheter related venous thrombosis occurring > 1 month before Cycle 1 Day 1).
  • Cohort 2: Arterial thrombotic or embolic events such as cerebrovascular accident (including transient ischemic attacks) within the last 12 months.
• Participant has any unresolved National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) (version 5.0) Grade > 2 toxicity at the Screening visit. Note: Participant receiving ongoing hormone replacement therapy for endocrine immune-related AEs without clinical symptoms will not be excluded.
• Participant has had major surgery (e.g., requiring general anesthesia) within 30 days before screening, or has not fully recovered from surgery, or has major surgery planned during the time the participant is expected to participate in the study.
• Participant has/had febrile illness or symptomatic, viral, bacterial (including upper respiratory infection) or fungal (noncutaneous) infection within 28 days prior to day 1.
• Participant received a blood transfusion within 1 month of the first dose of study intervention.
• Participant has a history of impaired pituitary or adrenal gland function (e.g., Addison's disease, Cushing's syndrome).
• Participant has hemoglobin A1c (HbA1c) > 10% (if diabetes mellitus was previously diagnosed) or HbA1c > 8% (if diabetes mellitus was previously undiagnosed). (Excluded participant may be rescreened after referral and evidence of improved control of their condition.)
• Participant has jaundice or known current active liver disease from any cause, including hepatitis A (hepatitis A virus IgM positive, but testing for hepatitis A in screening is not required), hepatitis B (hepatitis B virus surface antigen positive, confirmed by hepatitis B virus DNA), or hepatitis C (hepatitis C virus antibody positive, confirmed by hepatitis C virus RNA).
• Participant has moderate or severe hepatic impairment (Child-Pugh Class B or C).
• Participant has a known history of human immunodeficiency virus (HIV) infection (HIV antibody positive).
• Participant has a body mass index > 40 kg/m2.
• Participant has a history of drug or alcohol abuse according to Diagnostic and Statistical Manual of Mental Disorders, 5th edition criteria within 2 years before screening.
• Participant received treatment with glucocorticoids greater than the equivalent of 10 mg per day of prednisone within 4 weeks prior to C1D1. The use of topical, intraocular, inhalational, intranasal or intra-articular glucocorticoids is permitted.
• Participant received treatment with herbal medications with known anti-cancer properties or known effects on prostate physiology within 4 weeks prior to Cycle 1 Day 1 (e.g., saw palmetto, St. John's wort, turmeric/curcumin). Participants must agree not to use herbal products during study participation.
• Participant is receiving current treatment with systemic ketoconazole, abiraterone acetate (AA) or any other cytochrome P450 17A1 (CYP17) inhibitor. Participant who has received systemic ketoconazole, AA or any other CYP17 inhibitor must have discontinued these agents ≥ 4 weeks prior to the first dose of study intervention.
• Participant received prior systemic treatment with a strong inducer or inhibitor of cytochrome p450 3A4 (CYP3A4) within 4 weeks of first dose of study intervention. Concomitant use of strong inducers or inhibitors of CYP3A4 are not permitted on study.
• Participant requires use of biotin (i.e., vitamin B7) or supplements containing biotin higher than the daily adequate intake of 30 μg. Note: Participant who switches from a high dose to a dose of 30 μg/day or less prior to first dose of study drug is eligible for study entry.
• Participant is required to use any prohibited medication on the List of Excluded Concomitant Medications.

• For mCRPC participants only: Participant has been treated with any of the following for prostate cancer, during the indicated time frame prior to enrollment:

  • Hormonal therapy (e.g., androgen receptor blockers [AR] antagonists, second-generation androgen receptor pathway inhibitors [including enzalutamide, apalutamide, darolutamide, rezvilutamide and AA], 5-alpha reductase inhibitors, estrogens, cyproterone acetate) within 4 weeks of C1D1. Note: Participant has been treated with bicalutamide within 6 weeks prior to enrollment is not permitted. Participant has been treated with all other GnRH analogues or antagonists is permitted.
  • Chemotherapy within 2 weeks or 5 half-lives of C1D1 (whichever is longer)
  • Biologic therapy within 4 weeks of C1D1
  • Immunotherapy within 4 weeks of C1D1
  • Radiation therapy (includes radioligands) within 4 weeks of C1D1

• For mHSPC participants only: Participant has received any prior pharmacotherapy, radiation therapy or surgery for metastatic prostate cancer (the following exceptions are permitted):

  • Up to 4 months of ADT with GnRH agonists or antagonists or orchiectomy (within 3 months prior to C1D1) with or without concurrent antiandrogens.
  • Participant may have 1 course of palliative radiation or surgical therapy to treat symptoms resulting from metastatic disease if it was administered at least 4 weeks prior to C1D1.
  • Up to 6 cycles of docetaxel therapy, with the last dose of docetaxel ≤ 2 months prior to C1D1. A participant who has received docetaxel should have maintained a response to docetaxel of stable disease or better, by imaging and PSA, prior to C1D1.
  • Up to 6 months of ADT with GnRH agonists or antagonists or orchiectomy with or without concurrent antiandrogens prior to C1D1 if subject was treated with docetaxel, with no radiographic evidence of disease progression or rising PSA levels prior to C1D1.
• Participant has received any investigational therapy within 4 weeks or 5 half-lives (whichever is longer) prior to C1D1.
• Participant has received ASP5541 previously.
• Participant has absolute neutrophil count < 1500/μL, platelet count < 100000/μL or hemoglobin < 9 g/dL (6.2 mmol/L) or international normalized ratio (INR) ≥ 1.5 (unless participant is taking oral anticoagulants in which case INR ≤ 2.0 is permitted) at Screening. Note: Participant may not have received any growth factors within 7 days or blood transfusions within 28 days prior to the hematology values obtained at Screening.
• Participant has serum total bilirubin > 1.5 x upper limit of normal (ULN) (or > 3 x ULN for participants with documented Gilbert's disease), or serum alanine aminotransferase or aspartate aminotransferase > 2.5 x ULN at Screening.
• Participant does not have adequate renal function defined as a calculated creatinine clearance < 30 mL/min as determined by a validated algorithm for calculating creatinine clearance.
• Participant has serum albumin < 3.0 g/dL (30 g/L) at Screening.
• Participant has a known or suspected hypersensitivity to ASP5541, prednisone, or any components of the formulations used.
• Participant has a gastrointestinal disorder affecting absorption.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1 (mCRPC) Group A; Participants will receive ASP5541 every 12 weeks + prednisone/prednisolone twice daily	Drug: Prednisolone; Oral; Drug: Prednisone; Oral; Drug: ASP5541; Intramuscular Injection; Other Names: PRL-02; Drug: Adrenocorticotropic hormone; Intramuscular or intravenous injection
Active Comparator: Cohort 1 (mCRPC) Group B; Participants will receive abiraterone acetate once daily + prednisone/prednisolone twice daily	Drug: Prednisolone; Oral; Drug: Prednisone; Oral; Drug: abiraterone acetate; Oral; Drug: Adrenocorticotropic hormone; Intramuscular or intravenous injection
Experimental: Cohort 2 (mHSPC) Group A (Safety Run In); Participants will receive ASP5541 every 12 weeks	Drug: ASP5541; Intramuscular Injection; Other Names: PRL-02; Drug: Adrenocorticotropic hormone; Intramuscular or intravenous injection
Experimental: Cohort 2 (mHSPC) Group B; Participants will receive ASP5541 every 12 weeks	Drug: ASP5541; Intramuscular Injection; Other Names: PRL-02; Drug: Adrenocorticotropic hormone; Intramuscular or intravenous injection
Active Comparator: Cohort 2 (mHSPC) Group C; Participants will receive abiraterone acetate once daily + prednisone/prednisolone once daily	Drug: Prednisolone; Oral; Drug: Prednisone; Oral; Drug: abiraterone acetate; Oral; Drug: Adrenocorticotropic hormone; Intramuscular or intravenous injection
Experimental: Cohort 3 (mCRPC or mHSPC) Japanese Participants Only; Participants will receive ASP5541 every 12 weeks + prednisone/prednisolone twice daily (for mCRPC) or prednisone/prednisolone once daily (for mHSPC)	Drug: Prednisolone; Oral; Drug: Prednisone; Oral; Drug: ASP5541; Intramuscular Injection; Other Names: PRL-02; Drug: Adrenocorticotropic hormone; Intramuscular or intravenous injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of androgen receptor pathway inhibitor (ARPI) -naïve metastatic castration-resistant prostate cancer (mCRPC) participants with Prostate Specific Antigen (PSA) decline ≥ 90% (Cohort 1)	PSA will be recorded from blood sample.	Up to 37 months
Rate of no mineralocorticoid toxicity (Cohort 2 Group A, Safety run-in)	No mineralocorticoid toxicity is defined as experiencing neither Grade ≥ 1 hypokalemia nor Grade ≥ 2 hypertension.	Up to 37 months
Proportion of metastatic hormone-sensitive prostate cancer (mHSPC) participants with prostate-specific antigen (PSA) ≤ 0.2 ng/mL (Cohort 2)	PSA will be recorded from blood sample.	At 8 months
Dose-limiting toxicities (DLTs) (Cohort 3)	A DLT is defined as any event meeting the DLT criteria occurring during the first 28 days of treatment regardless of attribution to the study drug unless it is clearly related to disease progress or intercurrent illness.	Up to Day 28
Number of participants with Adverse Events (AEs) (Cohort 3)	AEs will be coded using MedDRA. An AE is any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention.	Up to 39 months
Number of Participants With Serious Adverse Events (SAEs) (Cohort 3)	An SAE is defined as any untoward medical occurrence that, at any dose: Results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is congenital anomaly/birth defect or other situations.	Up to 39 months
Number of participants with laboratory value abnormalities and/or AEs (Cohort 3)	Number of participants with potentially clinically significant laboratory values.	Up to 37 months
Number of participants with electrocardiogram (ECG) abnormalities and/or AEs (Cohort 3)	Number of participants with potentially clinically significant ECG values.	Up to 36 months
Number of participants with vital sign abnormalities and/or AEs (Cohort 3)	Number of participants with potentially clinically significant vital sign values.	Up to 37 months
Number of participants with physical exam abnormalities and/or AEs (Cohort 3)	Number of participants with potentially clinically significant physical exam values.	Up to 36 months
Eastern Cooperative Oncology Group (ECOG) Performance Status (Cohort 3)	The ECOG scale will be used to assess performance status. Grades range from 0 (fully active) to 5 (dead). Negative change scores indicate an improvement. Positive scores indicate a decline in performance.	Up to 36 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Radiographic progression-free survival (rPFS)	Radiographic progression-free survival (rPFS) is defined as the time from the date of randomization/first dose date until the date of radiological progressive disease (PD) per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) and Prostate Cancer Working Group 3 (PCWG3) as determined by investigator or death from any cause.	Up to 84 months
Prostate-specific antigen (PSA) decline ≥ 50% from baseline	Proportion of participants who had a PSA decline of ≥ 50% from baseline, confirmed by a second consecutive PSA assessment at least 3 weeks later.	Up to 37 months
PSA decline ≥ 90% (Cohorts 2 & 3 only)	Proportion of participants who had a PSA decline of ≥ 90% from baseline, confirmed by a second consecutive PSA assessment at least 3 weeks later.	Up to 37 months
PSA undetectable rate (≤ 0.2 ng/mL) (Cohorts 1 & 3)	Proportion of participants achieving a PSA level ≤ 0.2 ng/mL at any time post baseline.	Up to 37 months
PSA undetectable rate (≤ 0.02 ng/mL)	Proportion of participants achieving a PSA level ≤ 0.02 ng/mL at any time post baseline.	Up to 37 months
Time to PSA progression per PCWG3 criteria	Time from first dose date to the date of the first PSA value demonstrating a ≥ 25% increase and an absolute increase of ≤ 0.2 ng/mL above the nadir (i.e., the lowest PSA value observed post baseline or at baseline), which is confirmed by a second consecutive value at least 3 weeks later.	Up to 37 months
Objective response rate (ORR)	Proportion of participants who achieved a confirmed Complete Response (CR) or Partial Response (PR) in their soft tissue disease using RECIST v1.1 criteria and PCWG3 for bone disease.	Up to 84 months
Duration of response (DOR)	Time from first date of confirmed CR or confirmed PR until the date of radiological PD per RECIST v1.1 and PCWG3 as determined by investigator or death from any cause.	Up to 84 months
Best overall response (BOR)	The best response derived from all time points' overall responses (CR, PR, stable disease or non-CR/non-PD [for participants with no measurable disease at baseline], PD, not evaluable and not determined in order).	Up to 84 months
Number of participants with Adverse Events (AEs) (Cohorts 1 & 2)	AEs will be coded using MedDRA. An AE is any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention.	Up to 39 months
Number of Participants With Serious Adverse Events (SAEs) (Cohorts 1 & 2)	An SAE is defined as any untoward medical occurrence that, at any dose: Results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity is congenital anomaly/birth defect or other situations.	Up to 39 months
Number of participants with laboratory value abnormalities and/or AEs (Cohorts 1 & 2)	Number of participants with potentially clinically significant laboratory values.	Up to 37 months
Urine potassium (Cohort 2)	Potassium level will be recorded from urine sample.	Up to 37 months
Urine creatinine (Cohort 2)	Creatinine level will be recorded from urine sample.	Up to 37 months
Number of participants with electrocardiogram (ECG) abnormalities and/or AEs (Cohorts 1 & 2)	Number of participants with potentially clinically significant ECG values/cardiac monitoring.	Up to 36 months
Number of participants with vital sign abnormalities and/or AEs (Cohorts 1 & 2)	Number of participants with potentially clinically significant vital sign values.	Up to 37 months
Number of participants with physical exam abnormalities and/or AEs (Cohorts 1 & 2)	Number of participants with potentially clinically significant physical exam values.	Up to 36 months
ECOG Performance Status (Cohort 1 & 2 only)	The ECOG scale will be used to assess performance status. Grades range from 0 (fully active) to 5 (dead). Negative change scores indicate an improvement. Positive scores indicate a decline in performance.	Up to 36 months
Number of participants with testosterone suppression to ≤ 1 ng/dL, or achieves a ≥ 90% reduction from baseline	Testosterone value will be recorded from blood sample.	Up to 37 months
Mean testosterone value by timepoint	Testosterone value will be recorded from blood sample.	Up to 37 months
Time to pain progression	Time to pain progression defined using pain scores from the Brief Pain Inventory - Short form (BPI-SF) and opiate analgesic use will be evaluated.	Up to 36 months
Median time to testosterone suppression of levels ≤ 1 ng/dL	Time to testosterone suppression is defined as time from date of randomization/first dose date until testosterone suppression to ≤ 1 ng/mL.	Up to 37 months

Collaborators and Investigators

• Sponsor: Astellas Pharma Global Development, Inc.
• Investigators: Study Director: Medical Monitor, Astellas Pharma Global Development, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): June 19, 2025
• Primary Completion (Estimated): May 31, 2032
• Study Completion (Estimated): May 31, 2032

Study Registration Dates

• First Submitted: May 27, 2025
• First Submitted That Met QC Criteria: May 27, 2025
• First Posted (Actual): June 5, 2025

Study Record Updates

• Last Update Posted (Actual): July 7, 2026
• Last Update Submitted That Met QC Criteria: July 3, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: ASP5541; PRL-02
• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Prostatic Diseases; Male Urogenital Diseases; Prostatic Neoplasms; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Hypothalamic Hormones; Peptide Hormones; Neuropeptides; Peptides; Amino Acids, Peptides, and Proteins; Nerve Tissue Proteins; Proteins; Polycyclic Compounds; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Pregnadienetriols; Pregnadienediols; Androstenes; Androstanes; Pituitary Hormones; Pituitary Hormones, Anterior; Melanocortins; Pro-Opiomelanocortin; Abiraterone Acetate; Prednisone; Prednisolone; Adrenocorticotropic Hormone
• Other Study ID Numbers: 5541-CL-0201

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Access to anonymized individual participant level data collected during the study, in addition to study-related supporting documentation, is planned for studies conducted with approved product indications and formulations, as well as compounds terminated during development. Studies conducted with product indications or formulations that remain active in development are assessed after study completion to determine if Individual Participant Data can be shared. Further details on Astellas' data sharing policy can be found at https://www.clinicaltrials.astellas.com/transparency/.
• IPD Sharing Time Frame: Access to participant level data is offered to researchers after publication of the primary manuscript (if applicable) and is available as long as Astellas has legal authority to provide the data.
• IPD Sharing Access Criteria: Researchers must submit a proposal to conduct a scientifically relevant analysis of the study data. The research proposal is reviewed by an Independent Research Panel. If the proposal is approved, access to the study data is provided in a secure data sharing environment after receipt of a signed Data Sharing Agreement.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No