Mirdametinib Monotherapy in Adults With Neurofibromatosis 1 (NF1) and Cutaneous Neurofibromas (cNF).

Recruiting now · Phase 1/Phase 2

Conditions studied: NF1, Cutaneous Neurofibroma, Monotherapy

In brief

This is a Phase 1/2a, open-label, non-randomized, multi-dose study of mirdametinib monotherapy in adults with NF1 and cNF. In both Phases of the study, participation in the study will comprise three periods: screening, treatment and post-study safety follow-up to be performed at the NF1 and cNF specialty center: Johns Hopkins University.

Key facts

Study ID

NCT06159166

Run by

Johns Hopkins University

People needed

24

Starts

2024-02-12

Expected to finish

2028-11-15

Last updated by the study team

2026-04-13

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• Meet the diagnostic criteria for NF12
• ≥ 18 years of age
• Have a minimum of 24 measurable cNF (2 target areas of ≥6 measurable cNF)
• a. Measurable is defined as: i. non-pedunculated (no stalk) ii. surrounded by uninvolved skin and not adjacent to another cNF lesion iii. measuring ≥ 0.5 cm in the longest diameter and ≥ 0.5 cm in height iv. the 24 cNF must be located in two Target Areas. One target area must be located on the back and must have at least 6 measurable cNF. The second target area can be in any of the following body regions with at least 6 cNF: head and neck; upper extremities; anterior chest wall, anterior abdominal wall; pelvic region/gluteal region; lower extremities.
• Participants must have cNF that meet eligibility criteria located within the two study designated target areas or outside of the target areas amenable to biopsy. If biopsy is taken within the target area there must be a minimum of 6 cNF remaining for long term surveillance after biopsy. Participants must be willing to undergo pre-, and on-treatment tumor biopsies providing fresh tumor tissue; there should be no contraindication for serial biopsy
• Karnofsky performance level of ≥ 80%.
• Adequate organ and bone marrow function as defined by the following Screening laboratory values:
• Absolute neutrophil count ≥ 1500 cells/µL;
• Platelets ≥ 100 x 103/µL;
• Hemoglobin ≥ 9.5 g/dL;
• Serum albumin ≥ 2.8 g/dL;
• Calculated creatinine clearance at Screening ≥ 60 mL/min (by Cockcroft-Gault formula) OR a normal serum creatinine.
• Participant is willing and able to comply with all aspects of the protocol
• Ability to understand and the willingness to sign written informed consent document(s).
• Women of childbearing potential (WOCBP) must not be pregnant or breastfeeding during any portion of the study and must use an adequate method to avoid pregnancy during the study period and for 6 months after treatment conclusion and agrees not to donate eggs (ova, oocytes) for the purpose of reproduction during the study and for a period of 6 months after last dose of study treatment. The Investigator should evaluate the effectiveness of the contraceptive method in relationship to the first dose of study treatment (see the Approved Methods of birth control listed below).
• In order for a woman to be determined not of childbearing potential, she must have ≥ 12 months of non-therapy-induced amenorrhea or be surgically or medically sterile.
• WOCBP must have a negative serum pregnancy test result at Screening and a negative urine pregnancy test result at the Baseline visit prior to the first dose of study treatment.
• The Investigator is responsible for review of medical history, menstrual history, and recent sexual activity to decrease the risk for inclusion of a woman with an early undetected pregnancy.
• Male participants are eligible to participate if they agree to the following during the treatment period and for at least 90 days after the last dose of study treatment:
• Refrain from donating sperm
• PLUS either:
• Be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis) and agree to remain abstinent until 90 days after the last study drug treatment; OR
• Must agree to use a male condom when having sexual intercourse with a WOCBP and their female partner must utilize one the approved methods of birth control below:
• Approved Methods of birth control for this study are:
• Total abstinence

You may not qualify if…

• Participant has a altered screening values:
• alanine transaminase (ALT) value of > 2.0 x upper limit of normal (ULN);
• total bilirubin value of > 1.5 x ULN (isolated bilirubin > 1.5 x ULN is acceptable if bilirubin is fractionated and direct bilirubin < 35%);
• Participant has a history of malignancy associated hypercalcemia;
• Participant has an active parathyroid disorder, hyperphosphatemia at Screening (serum phosphorus > 1 x ULN), or serum calcium (mg/dL) x serum phosphorus (mg/dL) product > 70 at Screening;
• Any clinically significant active or known history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones);
• Hepatitis serology will be tested at Screening. Participants who are hepatitis B surface antigen (HBsAg) positive or hepatitis C virus (HCV) antibody positive at Screening must not be enrolled until further definite testing with hepatitis B virus (HBV) deoxyribonucleic acid (DNA) titers is < 500 IU/mL or HCV ribonucleic acid (RNA) polymerase chain reaction test is negative;
• Lymphoma, leukemia, or any malignancy (including malignant glioma or MPNST) within the past 5 years except for basal cell or squamous epithelial carcinomas of the skin that have been resected with no evidence of metastatic disease for 3 years;
• Breast cancer within the past 3 years;
• Active optic glioma or other low-grade glioma requiring treatment with chemotherapy or radiation therapy.
• a. Participants not requiring treatment are eligible. Ophthalmological findings secondary to long-standing optic pathway glioma (such as visual loss, optic nerve pallor or strabismus) or long-standing orbito-temporal PN (such as visual loss, strabismus) will NOT be considered a significant abnormality for the purposes of the study;
• Abnormal QT interval corrected by Fridericia's formula (> 450 msec for male participants, > 470 msec for female participants, or > 480 msec for participants with known bundle branch block), calculated from triplicate ECG readings taken approximately 2 to 3 minutes apart and averaged at Screening;
• Participant has experienced any of the following within 6 months (24 weeks) of signing informed consent/assent: clinically significant cardiac disease, myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft, cerebrovascular accident, transient ischemic attack, or symptomatic pulmonary embolism;
• A recorded LVEF < 55% at screening or within 3 years of signing informed consent/assent, OR has a history of congestive heart failure;
• Participants with a history of, or evidence of, retinal pathology on ophthalmologic examination that is considered a risk factor for central serous retinopathy, retinal vein occlusion (RVO), or neovascular macular degeneration. Participants will be excluded from study participation if they have any of the following risk factors for RVO at Screening:
• Intraocular pressure > 21 mmHg;
• Serum cholesterol > 300 mg/dL;
• Serum triglycerides > 300 mg/dL;
• Hyperglycemia (fasting blood glucose > 125 mg/dL or random blood glucose > 200 mg/dL);
• Hypertension (BP ≥ 140/90 mm Hg)
• History of glaucoma;
• Known history of a positive human immunodeficiency virus (HIV) antibody test;
• Known malabsorption syndrome or preexisting gastrointestinal conditions that may impair absorption of mirdametinib (e.g., gastric bypass, lap band, or other gastric procedures). Delivery of mirdametinib via nasogastric tube or gastrostomy tube is not allowed.
• Previously treated with MEK inhibitor including mirdametinib (PD-0325901) and had to stop treatment due to adverse event.
• Currently receiving therapy with a MEK inhibitor including mirdametinib (PD-0325901) or treated with a MEK inhibitor in the 12 months prior to prior to first dose of study treatment.

Where it is running

• Johns Hopkins Hospital — Baltimore, Maryland, United States (enrolling)

Full record on ClinicalTrials.gov

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