Actively Recruiting
A Phase 1/2a Open-label, Multicenter Dose Finding Study to Evaluate the Safety and Anti-tumor Activity of Mirdametinib Monotherapy in Adults With Neurofibromatosis 1 (NF1) and Cutaneous Neurofibromas (cNF).
Led by Johns Hopkins University · Updated on 2026-04-13
24
Participants Needed
1
Research Sites
52 weeks
Total Duration
On this page
Sponsors
J
Johns Hopkins University
Lead Sponsor
S
SpringWorks Therapeutics, Inc.
Collaborating Sponsor
AI-Summary
What this Trial Is About
Researchers are evaluating mirdametinib monotherapy in adults with Neurofibromatosis 1 (NF1) and cutaneous neurofibromas (cNF). This Phase 1/2a, open-label, non-randomized study aims to find safe and effective doses of mirdametinib and assess its anti-tumor activity. The study is conducted at Johns Hopkins University and includes adults with NF1 and measurable cNF who seek systemic treatment due to symptoms like disfigurement, pain, or itching. The study has two phases. Phase 1 tests up to four different dose regimens of mirdametinib, given continuously or intermittently (3 weeks on, 1 week off) in 28-day treatment cycles to determine recommended doses for Phase 2a. Phase 2a evaluates the safety and effectiveness of up to two selected doses. Participants receive the study drug until stopping criteria such as treatment completion, disease progression, intolerance, or withdrawal are met. Treatment periods end with the last dose, followed by 30 days of study completion monitoring. Participants undergo screening, treatment, and a post-study safety follow-up at the specialty center. They will be monitored through clinical assessments, laboratory tests, tumor biopsies, and performance evaluations. The main outcomes measured include mirdametinib safety, determination of recommended doses, and preliminary anti-tumor effects. The study continues until participants stop treatment due to various reasons or complete up to 48 treatment cycles.
CONDITIONS
Brief Title
Mirdametinib Monotherapy in Adults With Neurofibromatosis 1 (NF1) and Cutaneous Neurofibromas (cNF).
Who Can Participate
Eligibility Criteria
You may qualify if you...
- Meet the diagnostic criteria for Neurofibromatosis 1 (NF1)
- Be 18 years of age or older
- Have a minimum of 24 measurable cutaneous neurofibromas (cNF) in two target areas, with at least 6 measurable cNF on the back
- Have cNF eligible for biopsy and be willing to undergo pre- and on-treatment tumor biopsies
- Karnofsky performance status of 80% or higher
- Adequate organ and bone marrow function as defined by specific laboratory values
- Willing and able to comply with all aspects of the study protocol
- Ability to understand and sign informed consent
- Women of childbearing potential must not be pregnant or breastfeeding and must agree to use effective birth control during and for 6 months after treatment
- Male participants must agree to use contraception or abstain from heterosexual intercourse during treatment and for 90 days after last dose
You will not qualify if you...
- Alanine transaminase (ALT) above 2 times the upper limit of normal
- Total bilirubin above 1.5 times the upper limit of normal unless fractionated direct bilirubin is less than 35%
- History of malignancy-associated hypercalcemia
- Active parathyroid disorder or elevated serum phosphorus or calcium-phosphorus product
- Clinically significant liver disease or hepatic/biliary abnormalities except Gilbert's syndrome or asymptomatic gallstones
- Positive hepatitis B surface antigen or hepatitis C antibody without confirmed low viral load
- History of lymphoma, leukemia, or any malignancy within past 5 years except certain skin cancers
- Breast cancer within past 3 years
- Active optic glioma or low-grade glioma requiring treatment
- Abnormal corrected QT interval on ECG
- Recent significant cardiac events within 6 months
- Left ventricular ejection fraction below 55% or history of congestive heart failure
- Retinal pathology or risk factors for retinal vein occlusion
- History of glaucoma
- Known HIV infection
- Malabsorption syndrome or gastrointestinal conditions impairing drug absorption
- Previous treatment with MEK inhibitors causing adverse events
- Current or recent treatment with MEK inhibitors within 12 months
- Radiation therapy within 6 months prior to first dose
- Pregnant or breastfeeding women
- Participation in other non-observational clinical studies within 28 days
- Known sensitivity or allergy to study drug components
- Recent use of systemic or ocular glucocorticoid therapy
- Severe or uncontrolled medical or social conditions that could affect study participation
- Use of pan-cytochrome P450 inducers within 14 days prior to first dose
AI-Screening
AI-Powered Screening
Complete this quick 3-step screening to check your eligibility
Your Study Journey
Duration - 2 to 4 weeks
Participants are screened for eligibility to participate in the trial.
1 screening and enrollment visit
Duration - Up to 48 cycles of 28 days each (approximately 4 years), or until disease progression, intolerance, withdrawal, or investigator decision
Participants receive mirdametinib monotherapy in 28-day cycles. Phase 1 tests safety of multiple dose regimens administered continuously or intermittently. Phase 2a tests safety and efficacy of recommended phase 2 doses.
Participants attend regular visits corresponding to each treatment cycle, with dosing schedules of continuous or 3 weeks on/1 week off depending on dose regimen
Duration - 30 days
Participants are followed for safety for 30 days after the last dose of study treatment.
1 follow-up visit (in-person)
Trial Site Locations
Total: 1 location
1
Johns Hopkins Hospital
Baltimore, Maryland, United States, 21287
Actively Recruiting
Research Team
C
Carlos Romo, MD
J
Joshua Roberts
How is the study designed?
Study Type
INTERVENTIONAL
Masking
NONE
Allocation
NON_RANDOMIZED
Model
SEQUENTIAL
Primary Purpose
TREATMENT
Number of Arms
2
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