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 end of treatment if ≥ 18 years of age. 
• Participant has adequate organ and bone marrow function.
• Participant can swallow capsules whole if the capsule dosage form is being utilized. This criterion does not apply if participant is utilizing the dispersible tablet dosage form of study treatment;

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 PD-0325901. 
• Participant has received NF1 PN-targeted therapy within 45 days. 
• 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.