Clinical Trial 23695

• Overview

  Study Title:

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

  Summary:

  This is a research study to test a new investigational treatment, called ASP5541, for prostate cancer. ASP5541 has not been approved by any regulatory agencies. The active ingredient of ASP5541 is Abiraterone, which works by lowering the amount of male hormone in the body. ASP5541 may cause the growth and spread of prostate cancer to slow down.

  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

• Treatments

  Therapies:

  Androgen biosynthesis inhibitors; Androgen deprivation therapy (ADT); Androgen receptor pathway inhibitor

  Medications:

  ADT (); ASP5541 (); Abiraterone acetate (); Buserelin (); Decapeptyl SR (Triptorelin); Degarelix (); Histrelin (); Leuprolide acetate (); Leuprolide mesylate (); Prednisone or Prednisolone (); Relugolix (Orgovyx); Triptorelin (); Zytiga (Abiraterone acetate); goserelin acetate (Zoladex)

• Inclusion Criteria

  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. Inclusion Criteria for Cohort 1
  • Participant has been diagnosed with mCRPC 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 has evidence of disease progression defined as at least 1 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 PD on CT/MRI per 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 at least 1 wk 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.
  • 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). NOTE: Participants who have not had a bilateral orchiectomy must have a plan to maintain effective GnRH analogue therapy for the duration of the study.
  • Participant has a serum testosterone level > Participant is able to swallow AA. Inclusion Criteria for Cohort 2
  • Participant has been diagnosed with mHSPC documented by metastatic lesions on a bone scan, CT, MRI or PSMA-PET.
  • Participant must have started castration therapy (i.e., medical or surgical) at least 14 days prior to Cycle 1 Day 1. NOTE: A participant who has not had a bilateral orchiectomy must have a plan to maintain effective GnRH analogue therapy for the duration of the study.
  • Participant should have a baseline morning serum cortisol of ≥ 14 mcg/dL.
  • Participant is able to swallow AA.
  • For Groups B and C, participant has accessible archival tumor tissue from the primary tumor (preferred) or metastatic site (excluding bone) for which source and availability have been confirmed prior to study treatment.

• Exclusion Criteria

  Exclusion Criteria:
  • 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.
  • Known active central nervous system (CNS) metastases. NOTE: a participant with CNS metastases that have been treated with surgery and/or radiation therapy, who is no longer taking pharmacologic doses of glucocorticoids and is neurologically stable, is eligible.
  • 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 participant is currently in remission and has been in remission for ≥ 2 years Any other cancer from which participant has been disease-free for ≥ 5 years
  • Has any unresolved National Cancer Institute - Common Terminology Criteria for Adverse Events (NCI-CTCAE) (v5.0) 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.
  • Participant has had major surgery (e.g., requiring general anesthesia) within 90 days before screening, or will not have 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 Cycle 1 Day 1.
  • Participant received a blood transfusion within 1 month of Cycle 1 Day 1.
  • 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% 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).
  • Participant has jaundice or known current active liver disease from any cause, including hepatitis A (hepatitis A virus immunoglobulin M (IgM) positive, but testing for hepatitis A in screening is not required), hepatitis B [hepatitis B surface antigen (HBsAg) positive, or hepatitis B virus (HBV) DNA positive if HBsAg negative/anti-HBc positive]), or hepatitis C virus (HCV) antibody positive, confirmed by HCV 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. No HIV testing is required unless mandated by a local health authority.
  • 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 (DSM-5) criteria within 2 yrs before screening.
  • Participant has received treatment with glucocorticoids greater than the equivalent of 10 mg per day of prednisone within 4 wks prior to Cycle 1 Day 1. The use of topical, intraocular, inhalational, intranasal or intra-articular glucocorticoids is permitted.
  • Participant received treatment with herbal medications within 4 wks prior to Cycle 1 Day 1 (e.g., saw palmetto). Participants must agree not to use herbal products during study participation.
  • Participant is receiving current treatment with systemic ketoconazole or any other cytochrome 450 (CYP17) inhibitor. Participants who have received systemic ketoconazole or any other CYP17 inhibitor must have discontinued these agents ≥ 4 wks prior to Cycle 1 Day 1.
  • Other exclusions apply

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