Background: Ciclopirox (CPX) is an antifungal agent contained in a number of FDA-approved topical drug products. CPX possesses anticancer activity in a number of in vitro and in vivo preclinical models, however, it’s clinical utility is limited due to low oral bioavailabilty, gastrointestinal toxicity, and poor water solubility. Ciclopirox Prodrug (CPX-POM) selectively delivers its active metabolite, CPX, to the entire urinary tract following systemic administration. In a chemical carcinogen mouse model of bladder cancer, CPX-POM treatment resulted in significant decreases in bladder weight, a clear migration to lower stage tumors, dose-dependent reductions in Ki67 and PCNA staining, and inhibition of Notch 1 and Wnt signaling pathways. Methods: Study CPX-POM-001 (NCT03348514) is an ongoing US multicenter, Phase I, open-label, dose escalation study to evaluate dose-limiting toxicities (DLTs), define the maximum tolerated dose (MTD), and to determine the recommended Phase II dose of IV CPX-POM. Approximately 24 patients with any histologically- or cytologically-confirmed solid tumor type refractory to standard therapy, and also meet other standard Phase I eligibility criteria, will be enrolled in dose escalation cohorts. The MTD will be defined as the dose BELOW that dose which causes DLTs in ≥33% of patients. Safety and tolerability will be based on an assessment of adverse events, physical examinations, vital signs, electrocardiogram, clinical laboratory tests, ophthalmologic assessments, and concomitant medications. Single dose and steady-state pharmacokinetics of CPX-POM, CPX and ciclopirox glucuronide are being characterized in both plasma and urine. Urine ß-glucuronidase activity is also being determined. Single and multiple dose pharmacodynamics of CPX-POM are being characterized by measuring circulating biomarkers of Wnt and Notch cell signaling pathways. Enrollment began in January 2018 at a starting IV CPX-POM dose of 30 mg/m². Doses are currently being escalated in 100% increments until a ≥Grade 2 is encountered, at which point that cohort and all subsequent cohorts will follow a classical “3 + 3” dose escalation design. Clinical trial information: NCT03348514