Abstract
OBJECTIVES: The primary objective of the first-in-human (FIH) study was to evaluate the safety and tolerability of the manganese (Mn)-based contrast agent pegfosimer manganese in participants with newly diagnosed breast cancer, and secondary objectives included preliminary efficacy, and pharmacokinetics (PK) of the agent. METHODS: A single intravenous 1-hour infusion of pegfosimer manganese was administered to 2 cohorts; 6 participants at the starting dose of 10 μmol Mn/kg, followed by 8 participants at the expansion dose of 20 μmol Mn/kg, cohorts 1 and 2, respectively. The safety was evaluated based on reported adverse events (AEs), including serious AEs, physical examination, vital signs, electrocardiogram, and safety laboratory parameters. Magnetic resonance imaging (MRI) acquisition was performed precontrast and postcontrast to assess the clinical relevance of images in primary breast tumors, liver, and pancreas relative to reference tissue. PK parameters were calculated from a noncompartmental analysis of the plasma Mn concentrations versus time. RESULTS: There was a total of 29 AEs reported to all participants of the 2 cohorts. The AEs were mostly of mild to moderate severity and possibly or probably related to the contrast agent. No clinically significant changes in the safety laboratory parameters were reported, except for transiently elevated transaminases observed at the end of the infusion. Clinically relevant low-background MRI scans for clinical visualization of primary breast tumor, liver, and pancreas were obtained at the expanded dose level. Pegfosimer manganese has an initial plasma half-life of approximately 7 minutes. CONCLUSION: The FIH study of pegfosimer manganese demonstrated an acceptable safety profile and sufficient contrast enhancement for clinically relevant MRI sequences in participants with primary breast tumors.