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

SpringWorks Therapeutics

Status and phase

Active, not recruiting

Phase 2

Conditions

Neurofibromatosis Type 1 (NF1)

Plexiform Neurofibroma

Treatments

Drug: Mirdametinib (PD-0325901) oral capsule or dispersible tablet

Study type

Interventional

Funder types

Industry

Identifiers

NCT03962543

MEK-NF-201

Details and patient eligibility

About

This study evaluates mirdametinib (PD-0325901) in the treatment of symptomatic inoperable neurofibromatosis type-1 (NF1)-associated plexiform neurofibromas (PNs). All participants will receive mirdametinib (PD-0325901). Eligible participants may continue in a long-term follow-up phase.

Full description

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).

Mirdametinib (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 mirdametinib (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 mirdametinib (PD-0325901).

Enrollment

114 patients

Sex

All

Ages

2+ years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion criteria

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.