MEK Inhibitor Mirdametinib (PD-0325901) in Patients With Neurofibromatosis Type 1 Associated Plexiform Neurofibromas
Purpose
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.
Conditions
- Plexiform Neurofibroma
- Neurofibromatosis Type 1 (NF1)
Eligibility
- Eligible Ages
- Over 2 Years
- Eligible Sex
- All
- Accepts Healthy Volunteers
- No
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.
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.
Study Design
- Phase
- Phase 2
- Study Type
- Interventional
- Allocation
- N/A
- Intervention Model
- Single Group Assignment
- Intervention Model Description
- All participants will receive mirdametinib (PD-0325901) at a dose of 2 mg/m^2 twice daily (maximum dose of 4 mg twice daily), calculated based on body surface area. Dose will be administered in a 3-week on, 1-week off schedule.
- Primary Purpose
- Treatment
- Masking
- None (Open Label)
Arm Groups
| Arm | Description | Assigned Intervention |
|---|---|---|
|
Experimental Mirdametinib (PD-0325901) |
Mirdametinib (PD-0325901) capsule or dispersible tablet 2 mg/m^2 (maximum dose of 4 mg) by mouth twice daily |
|
More Details
- Status
- Active, not recruiting
- Sponsor
- SpringWorks Therapeutics, Inc.
Study Contact
Detailed 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).