MEK Inhibitor PD-0325901 in Patients With Neurofibromatosis Type 1 (NF1)-Associated Plexiform Neurofibromas

  • Interventional
  • Not Recruiting
  • NCT03962543
Eligibility Details Visit

A Phase 2b Trial of the MEK 1/2 Inhibitor (MEKi) PD-0325901 in Adult and Pediatric Patients With Neurofibromatosis Type 1 (NF1)-Associated Inoperable Plexiform Neurofibromas (PNs) That Are Causing Significant Morbidity

This study evaluates PD-0325901 in the treatment of symptomatic inoperable neurofibromatosis type-1 (NF1)-associated plexiform neurofibromas (PNs). All participants will receive PD-0325901.

Neurofibromas are benign peripheral nerve sheath tumors, which are classified as plexiform neurofibromas (PNs) if they extend longitudinally along a nerve and involve multiple fascicles. PNs are a major cause of morbidity and disfigurement in individuals with NF1, and as the tumor growth progresses, can cause a multitude of clinical deficits including pain and impaired physical function. PNs have the potential to undergo malignant transformation to Malignant Peripheral Nerve Sheet Tumors (MPNST).

     PD-0325901 is an orally delivered, highly selective small-molecule inhibitor of the dual specificity kinases, MEK1 and MEK2 (MAPK/ERK Kinase) which prevents the phosphorylation and subsequent activation of mitogen-activated protein kinase (MAPK).

     Previous studies of PD-0325901 demonstrated PN shrinkage and sustained inhibition of pERK. Reduced tumor volume indicated that cell proliferation or cell death may be altered in PNs with administration of PD-0325901.


Age Group
2 Years and up

Accepting Healthy Volunteers?

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.

         - Participant can swallow capsules whole.

        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 PD-0325901

         - Participant has received NF1 PN-targeted therapy within 28 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.

At a Glance

National Government IDNCT03962543


Lead SponsorSpringWorks Therapeutics, Inc.

Lead PhysicianJames Tonsgard


2 Years and up
Not Recruiting