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

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.
Competing Interests: D.V. received advisory support from AstraZeneca, grants or contracts from SpringWorks Therapeutics, Soleno Therapeutics, Levo Therapeutics, NFlection Therapeutics, and Takeda Pharmaceuticals; consulting fees from Sanofi Genzyme as well as payment or honoraria from SpringWorks Therapeutics and AstraZeneca. M.W. reports no conflicts of interest. H.S.H. has received advisory fees from AstraZeneca. M.L., P.S., K.S., and A.E. report employment at AstraZeneca. A.E., M.L., and K.S. own AstraZeneca stocks. F.L. owns AstraZeneca and AbbVie stocks.
(© The Author(s) 2024. Published by Oxford University Press, the Society for Neuro-Oncology and the European Association of Neuro-Oncology.)