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

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Astellas Pharma Global Development Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

17 Dec 2025 → ongoing

Decision date (initial)

2025-10-27

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Astellas Pharma Global Development, Inc.

External identifiers

EU CT number

2024-517653-27-00

ClinicalTrials.gov

NCT07005154

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacodynamic, Therapy, Pharmacogenomic, Efficacy, Prophylaxis, Pharmacokinetic, Safety

• To evaluate the efficacy of ASP5541 with prednisone or prednisolone compared with abiraterone acetate (AA) with prednisone or prednisolone in androgen receptor pathway inhibitor (ARPI)-naïve metastatic castration-resistant prostate cancer (mCRPC) participants (Cohort 1)
• To evaluate the safety of ASP5541 without steroids (Cohort 2 safety run-in) in ARPI-naïve metastatic hormone-sensitive prostate cancer (mHSPC) participants
• To evaluate the efficacy of ASP5541 without steroids compared with abiraterone acetate (AA) with prednisone or prednisolone in androgen receptor pathway inhibitor-naïve mHSPC participants (Cohort 2)
• To evaluate the safety of ASP5541 with prednisone or prednisolone in Japanese mCRPC or mHSPC participants (Cohort 3)

Secondary objectives 4

1. To further evaluate the efficacy of ASP5541 with and without prednisone or prednisolone compared with AA with prednisone or prednisolone
2. To evaluate the safety of ASP5541 with and without prednisone or prednisolone compared with AA with prednisone or prednisolone
3. To evaluate the pharmacodynamic profile of ASP5541 with and without prednisone or prednisolone compared with abiraterone acetate with prednisone or prednisolone
4. To evaluate pain progression following ASP5541 with and without prednisone or prednisolone compared with abiraterone acetate with prednisone or prednisolone

Conditions and MedDRA coding

Prostate Cancer

Regulatory references

Scientific advice from competent authorities

Food And Drug Administration, National Medical Products Administration, Pharmaceuticals And Medical Devices Agency

Plan to share 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/.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 12

1. 1. Adult participant aged at least 18 years at time of consent (adult age may vary according to local legislation).
2. 16. Participant has been diagnosed with mHSPC documented by metastatic lesions on a bone scan, CT, MRI or PSMA-PET. (Cohort 2)
3. 20. Participant has been diagnosed with mCRPC or mHSPC documented by metastatic lesions on a bone scan, CT, MRI, or PSMA-PET. (Cohort 3)
4. 2. Participant is diagnosed with histologically or cytologically confirmed adenocarcinoma of the prostate without neuroendocrine differentiation or small cell features.
5. 3. Participant has Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, or ECOG performance status of 2 if due to bone pain.
6. 4. Participant with mHSPC must have an estimated life expectancy of ≥ 12 months or >6 months if participant has metastatic castration-resistant prostate cancer (mCRPC).
7. 5. Participant is able to understand and comply with all study requirements and procedures, including completion of patient-reported outcome questionnaires, based on the assessment of the investigator.
8. 6. 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. ●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. ●Must not donate sperm during the treatment period and for 7 months after final ASP5541 or for 3 months after AA study intervention administration.
9. 7. Participant has provided informed consent, which includes compliance with the requirements and restrictions listed in the ICF and protocol
10. 9. Participant agrees not to participate in another interventional study while receiving ASP5541 in the present study.
11. 11. Participant has been diagnosed with mCRPC documented by metastatic lesions on a bone scan, CT, MRI or prostate-specific membrane antigen positron emission tomography (PSMA-PET). (Cohort 1)
12. 10. Participant should have normal serum potassium (within the local laboratory normal range) at screening without supplementation

Exclusion criteria 16

1. 1. Participant has any concurrent disease, infection or comorbid condition that interferes with the ability of the participant to participate in the study, which places the participant at undue risk or complicates the interpretation of data in the opinion of the investigator.
2. 3. 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 The medical monitor should be contacted for any questions regarding this exclusion criterion.
3. 5. 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: A participant receiving ongoing hormone replacement therapy for endocrine immune-related AEs without clinical symptoms will not be excluded.
4. 6. Participant has had major surgery (e.g., requiring general anesthesia) within 30 days before screening, or has not have fully recovered from surgery, or has major surgery planned during the time the participant is expected to participate in the study.
5. 7. Participant has/had febrile illness or symptomatic, viral, bacterial (including upper respiratory infection) or fungal (noncutaneous) infection within 28 days prior to Cycle 1 Day 1.
6. 8. Participant received a blood transfusion within 1 month of Cycle 1 Day 1.
7. 9. Participant has a history of impaired pituitary or adrenal gland function (e.g., Addison's disease, Cushing's syndrome).
8. 10. Participant has HbA1c > 10% and was previously diagnosed with diabetes mellitus. Participant has HbA1c > 8% and was not previously diagnosed with diabetes mellitus (excluded participants may be rescreened after referral and evidence of improved control of their condition).
9. 11. 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 [HBsAg positive, or HBV DNA positive if HBsAg negative/anti-HBc positive]), or hepatitis C (HCV antibody positive, confirmed by HCV RNA).
10. 12. Participant has moderate or severe hepatic impairment (Child-Pugh Class B or C).
11. 13. Participant has a known history of HIV infection. No HIV testing is required unless mandated by a local health authority.
12. 14. Participant has a body mass index > 40 kg/m2.
13. 15. Participant has a history of drug or alcohol abuse according to DSM-5 criteria within 2 years before screening.
14. 32. For Cohort 1: Prior treatment with a second-generation ARPI (e.g., AA, enzalutamide, apalutamide or darolutamide). NOTE: limited treatment with a second-generation ARPI in the neo-adjuvant, adjuvant or non-metastatic biochemically recurrent setting is permitted as long as there was no evidence of disease progression for at least 6 months following last dose.
15. 35, 38, 41. Participant has clinically significant cardiac disease.
16. 36. For Cohort 2: Prior treatment with a second-generation ARPI (e.g., AA, enzalutamide, apalutamide or darolutamide). Note: limited treatment with a second-generation ARPI in the neo-adjuvant, adjuvant or non-metastatic biochemically recurrent setting is permitted as long as there was no evidence of disease progression for at least 6 months following last dos

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 4

1. • Proportion of ARPI-naïve mCRPC participants with PSA decline ≥ 90% from baseline (Cohort 1)
2. • Rates of no mineralocorticoid toxicity, defined as experiencing neither Grade ≥ 1 hypokalemia nor Grade ≥ 2 hypertension (Cohort 2 safety-run in)
3. • Proportion of mHSPC participants with PSA ≤ 0.2 ng/mL at 8 months (Cohort 2)
4. • dose-limiting toxicities (DLTs), AEs, serious Adverse Events (SAEs), laboratory results (including chemistry, hematology and urinalysis), electrocardiograms (ECGs), vital signs, physical examinations and ECOG performance status scores (Cohort 3)

Secondary endpoints 6

1. • Radiographic progression-free survival (rPFS), defined as the time from date of randomization/first dose date until the date of radiological progressive disease (PD) per RECIST v1.1 and PCWG3 as determined by investigator or death from any cause • Prostate-specific antigen (PSA) decline ≥ 50% from baseline • PSA decline ≥ 90% from baseline (Cohorts 2 and 3 only)
2. • PSA undetectable rate (≤ 0.2 ng/mL) (Cohorts 1 and 3 only) • PSA undetectable rate (≤ 0.02 ng/mL) • Time to PSA progression per PCWG3 criteria • Objective response rate per RECIST v1.1 for soft tissue disease and PCWG3 for bone disease • Duration of response per RECIST v1.1 for soft tissue disease and PCWG3 for bone disease
3. • Best overall response per RECIST v1.1 for soft tissue disease and PCWG3 for bone disease
4. • AEs, SAEs, laboratory results (including chemistry, hematology, urinalysis • spot urine potassium and creatinine (Cohort 2 only) • ECGs, vital signs, physical examinations and ECOG performance status scores (Cohorts 1 + 2 only)
5. • Testosterone suppression to ≤ 1 ng/dL, or achieves a ≥ 90% reduction from baseline level • Mean testosterone values by time point • Median time to testosterone suppression of level ≤ 1 ng/dL
6. Time to pain progression defined using pain scores from the BPI-SF and opiate analgesic use.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 3

Comparator 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Astellas Pharma Global Development Inc.

Sponsor organisation

Astellas Pharma Global Development Inc.

Address

2375 Waterview Drive

City

Northbrook

Postcode

60062-6145

Country

United States

Scientific contact point

Organisation

Astellas Pharma Global Development Inc.

Contact name

Head of Clinical Trial Unit Regulatory Affairs

Public contact point

Organisation

Astellas Pharma Global Development Inc.

Contact name

Head of Clinical Trial Unit Regulatory Affairs

Third parties 12

Locations

5 EU/EEA countries · 24 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 71 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

8 submissions — initial application plus substantial / non-substantial modifications