A Phase I, Multicenter, Open-Label, Dose-Escalation, and Dose-Expansion Study to Evaluate the Safety, Pharmacokinetics, and Anti-Tumor Activity of ARX517 as Monotherapy and in Combination With Androgen Receptor Pathway Inhibitors in Subjects With Metastatic Prostate Cancer
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Study Summary
To assess the safety and tolerability of ARX517 in adult subjects with Metastatic Castration-Resistant Prostate Cancer (mCRPC).
To evaluate the safety, pharmacokinetics, and preliminary anti-tumor activity of ARX517 in adults with prostate cancer or other solid tumors whose disease is resistant or refractory to standard therapies.
The number of subjects in the dose-expansion will be based on the number of doses to be expanded for further evaluation of safety, PK, and clinical activity. Through dose levels one and two, no dose limiting toxicities have been observed. Ascending dose levels of ARX517 as a single agent will be administered until the recommended Phase 2 dose or maximum tolerated dose is determined.
To evaluate dose escalation and dose expansion
To evaluate the safety, pharmacokinetics, and preliminary evidence of anti-tumor activity of ARX517 in adults with mCRPC.
Key objectives include safety, PK and clinical efficacy. Baseline PSMA PET expression was not required for eligibility but was evaluated as a biomarker.
PK parameters were determined using noncompartmental analysis based on serum concentrations of TA, ADC, and pAF-AS269.
To evaluate ARX517 in patients with mCRPC resistant or refractory to prior therapies
- 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
- 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.
Clinical Study Information for Healthcare Providers
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