Key Inclusion Criteria:

   - Participant has documented NF1 mutation or a diagnosis of neurofibromatosis type 1
   (NF1) using National Institute of Health (NIH) Consensus Conference criteria inclusive
   of the presence of a plexiform neurofibroma (PN).

   - Participant has a PN that is causing significant morbidity.

   - Participant has a PN that cannot be completely surgically removed.

   - Participant has a target tumor that is amenable to volumetric MRI analysis.

   - Participant is willing to undergo a tumor biopsy pre and post treatment if ≥ 18 years
   of age.

   - Participant has adequate organ and bone marrow function.

Key Exclusion Criteria:

   - Participant has abnormal liver function or history of liver disease.

   - Participant has lymphoma, leukemia or any malignancy within the past 5 years (except
   for resected basal/squamous skin carcinomas without metastases within 3 years).

   - Participant has breast cancer within 10 years.

   - Participant has active optic glioma or other low-grade glioma requiring treatment.

   - Participant has abnormal QT interval corrected or other heart disease within 6 months.

   - Participant has a history of retinal pathology, risk factors for retinal vein
   occlusion or has a history of glaucoma.

   - Participant has known malabsorption syndrome or gastrointestinal conditions that would
   impair absorption of mirdametinib (PD-0325901).

   - Participant has received NF1 PN-targeted therapy within 45 days.

   - Participant previously received or is currently receiving therapy with mirdametinib
   (PD-0325901) or any other MEK1/2 inhibitor.

   - Participant has received radiation therapy within 6 months or has received radiation
   to the orbit at any time.

   - Participant is unable to undergo or tolerate MRI.

   - Participant has active bacterial, fungal or viral infection.

   - Participant has experienced other severe acute or chronic medical or psychiatric
   conditions within 1 year.