ARX517 as Monotherapy and in Combination Regimens in Subjects With Metastatic Castration-resistant Prostate Cancer

Open to males ages 18 years and up

• Male subjects ≥ 18 years at the first time of providing written informed consent.
• Histologically confirmed prostate adenocarcinoma.
• Documented metastatic disease and evidence of disease progression
• Castration-resistant prostate cancer defined as surgical or medical castration with serum testosterone levels of ≤ 50 ng/dL (1.73 nM) at Screening. For patients who have not undergone an orchiectomy, must be undergoing treatment with a luteinizing hormone-releasing hormone (LHRH) agonist or antagonist and must agree to continue such therapy while on study treatment.
• Ongoing therapy with (and willing to continue with) a gonadotropin-releasing hormone agonist or antagonist (unless prior orchiectomy) AND serum testosterone level < 50 ng/dL at Screening.
• Prior receipt of the following for metastatic prostate cancer:
  • at least two lines of treatment
  • at least two Food and Drug Administration (FDA)-approved therapies with at least one being a second-generation androgen receptor signaling inhibitor (e.g., abiraterone, darolutamide, apalutamide, or enzalutamide).
• Adequate blood counts

• Symptomatic and/or untreated central nervous system (CNS) metastases. Patients with asymptomatic, untreated CNS metastases are eligible provided they have been clinically stable (neurologically stable and not requiring steroids for at least 28 days prior to enrollment)
• History of any invasive malignancy (other than primary) within previous 2 years prior to the enrollment date that requires active therapy
• Marked baseline prolongation of QT/QT interval corrected for heart rate (QTc), e.g., a triplicate average QTc interval > 480 milliseconds (CTCAE Grade 1) using Fridericia's QT correction formula.
• Prior history of interstitial lung disease, pneumonitis, or other clinically significant lung disease within 12 months prior to enrollment date
• Clinically significant ocular findings by a qualified ophthalmologist or optometrist including active ocular infections or chronic corneal disorders
• Phase 1b combination cohort subjects only: Any gastrointestinal disorder, including stents, defects or malabsorption, that would interfere with absorption of orally administered study drug in the opinion of the investigator.
• Phase 1b combination cohort subjects only: Prior receipt of strong CYP2C8 inhibitors, strong CYP3A4 inducers, and CYP3A4, CYP2C9 and CYP2C19 substrates with a narrow therapeutic index within 14 days or five half-lives (if known), whichever is shorter, prior to enrollment. If discontinuation is medically not feasible, enrollment may be allowed with Sponsor approval.