Effect of food on selumetinib pharmacokinetics and gastrointestinal tolerability in adolescents with neurofibromatosis type 1-related plexiform neurofibromas

Selumetinib is approved for the treatment of pediatric patients with neurofibromatosis type 1 (NF1) who have symptomatic, inoperable plexiform neurofibromas (PN) in multiple countries, including the USA (≥2 years). Until recently, individuals had to take selumetinib twice daily (BID) in a fasted state. This study evaluated the effect of a low-fat meal on selumetinib PK parameters and gastrointestinal (GI) tolerability in adolescent participants with NF1-PN. Eligible participants aged ≥12–<18 years took 25 mg/m2 selumetinib BID with a low-fat meal (T1) for 28 days, followed by a 7-day washout, and then administration in a fasted state (T2) for another 28 days. Primary objectives were to evaluate the effect of a low-fat meal on AUC0−12,ss and GI tolerability after multiple selumetinib doses in T1 versus T2. Key secondary objectives were additional PK parameters, and adverse events (AEs). At primary data cut-off, all 24 participants completed T1, and 23 participants completed T2. There were no significant differences in AUC0−12,ss between T1 and T2. In T1 and T2, 29.2% and 33.3% participants, respectively, reported ≥1 GI AE. No GI AEs Grade ≥3, or serious AEs, or GI AEs resulting in treatment interruptions, discontinuation, or dose reductions were reported in T1 and T2. Dosing selumetinib with a low-fat meal had no clinically relevant impact on selumetinib AUC0−12,ss nor GI tolerability in adolescents with NF1-PN.