Safety, Preliminary Efficacy and Pharmacokinetics of ASN001 in Metastatic Castrate Resistant Prostate Cancer

A Phase 1/2, Open-Label, Uncontrolled, Multiple-Dose Escalation, Cohort Expansion And Extension Study To Evaluate The Safety, Tolerability, And Pharmacokinetics Of ASN001 In Subjects With Metastatic Progressive Castrate Resistant Prostate Cancer

This study will be conducted in three parts. Part A is a dose-escalation study to determine two safe and tolerable doses of ASN001 for men with metastatic castration resistant prostate cancer. Part A will also characterize the pharmacokinetics and pharmacodynamics of the ASN001 through blood sampling. Subjects in Part B will receive one of two doses identified in Part A to determine which one is more effective, and collect additional pharmacokinetic data. Part C is an extension for subjects completing either Part A or B.

Parts A and B will include a screening period (up to 28 days) and a 12-week treatment period. A subject with no serious adverse drug reactions and who is expected to benefit from continued treatment in the opinion of the investigator will have the opportunity to participate in the long-term extension (Part C). If the subject is not a candidate for or chooses not to participate in the long-term extension (Part C), a post-treatment period of 4 weeks will commence that concludes with an end-of-study visit.

Subjects participating in only Part A or Part B will have approximately 9 study site visits over 18 weeks. Part C will include monthly visits to the study site for 9 months. Thereafter, visits will occur every 3 months. A subject with stable disease or response may continue ASN001 treatment with the approval of the investigator; treatment can continue until a subject experiences an intolerable adverse event (AE) or disease progression, withdraws consent or until termination of the study by the sponsor. At the end of treatment, a post-treatment period of 4 weeks will commence that concludes with an end-of-study visit.

Part B of the study will not be completed as enrollment was halted after Part A (Phase 1)

Inclusion Criteria

• Histologically confirmed adenocarcinoma of the prostate.
• Ongoing androgen deprivation therapy with a luteinizing hormone-releasing hormone (LHRH) agonist or antagonist, or bilateral orchiectomy and serum testosterone level < 50 ng/dL (< 0.5 ng/mL, < 1.7 nmol/L) at screening
• Metastatic disease documented by computed tomography (CT)/magnetic resonance imaging (MRI) or bone scan.
• Progressive disease despite ongoing androgen deprivation therapy.
• Adequate liver, kidney, and bone marrow function
• Life expectancy of at least 3 months
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2 at screening
• Patients with prior cytotoxic chemotherapy are eligible to participate if they have been progression free for at least 12 months since the initiation of cytotoxic chemotherapy

Exclusion Criteria:

• Patients with rapidly progressive disease who are candidates for other approved therapies such as docetaxel, abiraterone, and enzalutamide.
• Prior therapy with abiraterone, orteronel, ketoconazole, or any other Cytochrome P450 (CYP) 17 lyase inhibitor; enzalutamide or other experimental androgen receptor antagonist; or experimental immunotherapy agent.
• History of impaired adrenal gland function
• Any investigational treatments for any condition within 4 weeks prior to the start of study treatment.
• Therapy with herbal products known to effect PSA, or estrogen within 30 days prior to the start of study medication
• Known gastrointestinal disease or condition that affects the absorption of ASN001, or difficulty swallowing large capsules.
• Use of systemic glucocorticoid (eg, prednisone, dexamethasone) within 14 days prior to the start of study medication
• Major surgery within 30 days of study medication
• Known brain metastasis
• Previous history of another cancer within 5 years, except completely removed basal or squamous cell skin cancer.
• Serious concurrent medical conditions including: serious heart disease, heart conduction abnormalities, persistent infection, uncontrolled psychiatric illness, liver cirrhosis, chronic liver disease, active or symptomatic viral hepatitis, any other condition that may place the subject at an increased risk or confound the results of the study.