Overview
This is a phase 1 study to assess the safety and tolerability of ARX517 in adult subjects with Metastatic Castration-Resistant Prostate Cancer (mCRPC).
Description
This is a first-in-human, Phase 1, multicenter, open-label study to evaluate the safety, PK, PDy, and preliminary anti-tumor activity of ARX517 in adult subjects with mCRPC with serum testosterone level < 50 ng/dL at screening who are resistant or refractory to standard therapies. Phase 1a (dose-escalation) and Phase 1b (dose-expansion) stages will identify the MTD and/or RDDs.
Eligibility
Key Inclusion Criteria:
- 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.
- 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
Key Exclusion Criteria:
- Use of chronic systemic glucocorticoids equivalent to > 10 mg prednisone daily. Note: short-term administration of systemic corticosteroids > 10 mg prednisone equivalent (e.g., for allergic reactions or management of immune- or infusion-related AEs) is allowed.
- 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 the previous 2 years prior to the enrollment date that requires active therapy or is at high risk of recurrence in the opinion of the investigator.
- Marked baseline prolongation of QT/QT interval corrected for heart rate (QTc), e.g., a triplicate-average QTc interval > 480 milliseconds (CTCAE Grade 2) using Fridericia's QT correction formula at any time within 28 days before enrollment, ongoing history of CTCAE Grade ≥2 QTc at enrollment, or anticipated need to perform repeat ECG evaluations to satisfy re-treatment criteria.
- 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 unless approved by the Medical Monitor.
- Peripheral neuropathy Grade ≥ 2 within 28 days prior to enrollment.