ID #479 Use of Mirdametinib for the Treatment of Neurofibromatosis Type 1–Associated Plexiform Neurofibromas (NF1-PN) in Patients with Prior Mitogen-Activated Protein Kinase (MAPK) Kinase Inhibitor (MEKi) Exposure
Rene McNall-Knapp, Nicholas Foreman, Andrea Franson, Lauren Weintraub, Kevin Bielamowicz, Molly Nickerson, Michael Weber, Armend Lokku, Racheal Bingham, Kelly Vallance, Angela HirbeAbstract
Background
Mirdametinib is the first approved MEKi for NF1-PN in adults and children. MEKis differ in selectivity, potency, and pharmacokinetics—characteristics that may impact efficacy and toxicity. However, data are limited on patient experiences with different MEKis after MEKi failure due to lack of efficacy or tolerability.
Methods
Patients with NF1-PN and prior MEKi exposure enrolled in the pivotal ReNeu trial of mirdametinib (n = 6 children; n = 4 adults) were evaluated post hoc for clinical outcomes (Table). Patient cases from SpringWorks Early Access Program will be described in the presentation.
Results
Four patients had PD at baseline. Mirdametinib treatment duration ranged from ∼8-40mo. All mirdametinib-treated patients had a BOR of PR or SD. Time to best percentage target PN volume change was 4.0-32.7mo. Of 5 patients who discontinued prior MEKi for PD or pain, 1 discontinued mirdametinib for PD. Of 3 patients who discontinued prior MEKi for toxicity, 2 discontinued mirdametinib for TRAEs.
Conclusions
In MEKi-exposed patients with NF1-PN, including those who discontinued prior MEKi due to toxicity/PD, observed mirdametinib outcomes suggest MEKi-exposed patients can benefit from mirdametinib treatment.
Support
SpringWorks Therapeutics, Inc