Multicenter phase 2b trial of mirdametinib for symptomatic neurofibromatosis type 1-associated plexiform neurofibroma

The multicenter phase 2b ReNeu trial in the US evaluated the MEK1/2 inhibitor mirdametinib for neurofibromatosis type 1-associated neurofibromas (NF1-PNs) in adults and children (aged 2-17 years). The primary endpoint was confirmed objective response rate, defined as proportion of patients with at least 20% reduction of target PN volume from baseline on consecutive scans during the 24-cycle treatment phase (3 weeks on/ 1 week off in 28-day cycles). Blinded independent central review ORR was 41% among adults and 52% among children during treatment. Median target PN volumetric best response was -41% in adults and -42% in children. Both cohorts reported significant and clinically meaningful improvement in patient- or parent proxy-reported worst tumor pain severity, pain interference, and health-related quality of life that began early and were sustained during treatment. The most commonly reported treatment-related adverse events were dermatitis acneiform and diarrhea, and nausea in adults and paronychia in children. The aiuthors conclude that mirdametinib demonstrated significant activity for NF1-PNs in adults and children.