Abstract
BACKGROUND: 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. METHODS: Eligible participants aged ≥ 12 to < 18 years took 25 mg/m(2) 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 AUC(0-12,ss) and GI tolerability after multiple selumetinib doses in T1 versus T2. Key secondary objectives were additional PK parameters and adverse events (AEs). RESULTS: At primary data cut-off, all 24 participants completed T1, and 23 participants completed T2. There were no significant differences in AUC(0-12,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. CONCLUSIONS: Dosing selumetinib with a low-fat meal had no clinically relevant impact on selumetinib AUC(0-12,ss) nor GI tolerability in adolescents with NF1-PN. TRIAL REGISTRATION CLINICALTRIALSGOV ID: NCT05101148.