Mirdametinib for Neurofibromatosis

(Mirda Trial)

Overseen By Joshua Roberts

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Johns Hopkins University

Must not be taking: MEK inhibitors, Glucocorticoids

Disqualifiers: Liver disease, Glaucoma, HIV, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 2

24 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment called mirdametinib for individuals with NF1, a genetic disorder that causes tumors on nerve tissue, and cNF, a specific type of non-cancerous tumor linked to NF1. The trial aims to assess mirdametinib's effectiveness in reducing these tumors and its safety for regular use. To qualify, participants must have at least 24 measurable cNF tumors in specific body areas. During the treatment period, participants will receive the study drug until certain conditions are met, followed by safety check-ups. As a Phase 1, Phase 2 trial, this research seeks to understand how the treatment works in people and measure its effectiveness in an initial, smaller group.

Do I need to stop my current medications to join the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot participate if you are currently receiving certain treatments like systemic glucocorticoids or specific enzyme inducers within 14 days before the study starts.

Is there any evidence suggesting that mirdametinib is likely to be safe for humans?

Research has shown that mirdametinib, a treatment under study for neurofibromatosis type 1 (NF1), is generally well-tolerated. Earlier studies reported side effects similar to those of other drugs that block certain proteins, suggesting a consistent safety record for mirdametinib. Importantly, the FDA has already approved mirdametinib for treating NF1 in both adults and children, indicating its safety for this use. However, like any treatment, side effects may occur. Discussing potential risks with a healthcare provider is always advisable. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for neurofibromatosis?

Unlike the standard treatments for neurofibromatosis, which primarily focus on managing symptoms or slowing tumor growth through surgery or radiation, Mirdametinib offers a different approach by targeting the MEK pathway, a key driver in the development of neurofibromas. This mechanism of action could potentially reduce tumor size and improve patient outcomes more effectively than current options. Researchers are excited because Mirdametinib might provide a less invasive and more targeted therapy, offering hope for better quality of life for patients with fewer side effects.

What evidence suggests that mirdametinib might be an effective treatment for neurofibromatosis?

Research has shown that mirdametinib may help treat neurofibromatosis type 1 (NF1). In one study involving adults and teens with plexiform neurofibromas (PNs) that couldn't be surgically removed, 42% of patients experienced at least a 20% reduction in tumor size. This finding suggests that mirdametinib can significantly reduce tumor size in many patients. The FDA has approved mirdametinib for treating NF1 with symptomatic, inoperable PNs, further supporting its effectiveness. These results provide strong evidence of its potential to help people with NF1. Participants in this trial will receive mirdametinib in either the Phase 1 or Phase 2 portion, where researchers will further evaluate its effects. ^{4 6 7 8 9}

Who Is on the Research Team?

Carlos Romo, MD

Principal Investigator

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Are You a Good Fit for This Trial?

Adults over 18 with Neurofibromatosis type 1 (NF1) and at least 12 measurable cutaneous neurofibromas (cNF). They must have a certain level of overall health, including specific blood cell counts and performance status. Participants need to be able to undergo tumor biopsies.

Inclusion Criteria

I have at least 24 measurable skin growths, with 2 areas having at least 6 each.

My eligible neurofibromas are in the study's specified areas or can be biopsied if outside those areas.

I can carry out normal activities with minimal symptoms.

Exclusion Criteria

I have had a heart problem in the last 6 months.

I have a history of eye problems related to the retina.

I have a condition that affects how my body absorbs medication.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment Phase 1

Participants receive mirdametinib in multiple dose regimens to identify the recommended phase 2 dose (RP2D). Treatment is administered continuously or intermittently in 28-day cycles.

Up to 24 cycles (28 days each)

Monthly visits (in-person)

Treatment Phase 2a

Participants receive mirdametinib at the RP2D to evaluate efficacy and safety. Treatment continues until disease progression, intolerance, or completion of 24 cycles.

Up to 24 cycles (28 days each)

Monthly visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment ends. The study ends 30 days after the last dose.

4 weeks

1 visit (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Mirdametinib

Trial Overview

The trial is testing Mirdametinib as a single-agent therapy for adults with NF1 and cNF. It's an open-label study, meaning both doctors and patients know what treatment is being given, conducted in multiple doses across three phases: screening, treatment, and follow-up.

How Is the Trial Designed?

Group I: Phase 2 Experimental Treatment 1 Intervention

For the Phase 2 portion, treatment will be administered based on recommended RP2D from Phase 1. All participants will receive study drug until: 1. cessation of study treatment due to death, intolerance, or withdrawal of consent from the study; 2. completion of 24 cycles of treatment (unless the investigator's benefit-risk assessment supports continued treatment; 3. disease progression; or 4. Investigator's decision. Treatment period ends with the administration of the last dose. The study ends 30 days after the last dose.

Group II: Phase 1 Experimental Treatment 1 Intervention

For the Phase 1 portion, treatment will be administered continuously (Dose regimens 1, 2, 4) or intermittently (Dose regimen 3; 3 weeks on/1 week off) in 28-day cycles). All participants will receive study drug until: 1. cessation of study treatment due to death, intolerance, or withdrawal of consent from the study; 2. completion of 24 cycles of treatment (unless the investigator's benefit-risk assessment supports continued treatment); 3. participants enroll in the phase 2a portion of the study; 4. disease progression; or 5. Investigator's decision. Treatment period ends with the administration of the last dose. The study ends 30 days after the last dose

Who Is Running the Clinical Trial?

Johns Hopkins University

Lead Sponsor

Trials

2,366

Recruited

15,160,000+

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Lead Sponsor

Trials

578

Recruited

33,600+

Neurofibromatosis Therapeutic Acceleration Program

Collaborator

Trials

3

Recruited

600+

SpringWorks Therapeutics, Inc.

Industry Sponsor

Trials

14

Recruited

900+

Published Research Related to This Trial

A high-throughput drug sensitivity platform was used to analyze tumor cell lines from patients with Neurofibromatosis type 1 (NF1) and type 2 (NF2), revealing that NF1-associated tumors are particularly sensitive to MEK and ERK inhibitors.

The platform effectively predicted the outcomes of clinical trials for treating neurofibromas, suggesting it could be a valuable tool for developing targeted therapies for NF-related tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comprehensive pharmacological profiling of neurofibromatosis cell lines. Guo, J., Grovola, MR., Xie, H., et al.[2020]

A young patient with neurofibromatosis type 1 (NF1) and recurrent glioblastoma showed a partial response to the MEK-inhibitor trametinib, but experienced significant cutaneous toxicity as a side effect.

Adding the BRAF-inhibitor dabrafenib to the treatment regimen helped alleviate the skin-related side effects, leading to a durable complete response and improved tolerance to the overall treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Durable Complete Response of a Recurrent Mesencephalic Glioblastoma Treated with Trametinib and Low-Dose Dabrafenib in a Patient with Neurofibromatosis Type 1. Awada, G., Serruys, D., Schwarze, JK., et al.[2020]

Selumetinib, a MEK inhibitor, has shown a remarkable overall response rate of 68% in children with neurofibromatosis type 1 (NF1) and symptomatic inoperable plexiform neurofibromas (PNs), leading to its FDA approval in May 2020.

Other targeted therapies, including cabozantinib and mirdametinib, have also demonstrated efficacy in adults with NF1, indicating a growing range of treatment options for this condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Novel molecular targeted therapies for patients with neurofibromatosis type 1 with inoperable plexiform neurofibromas: a comprehensive review. Solares, I., Viñal, D., Morales-Conejo, M., et al.[2021]

Selumetinib, a MEK inhibitor, is the first FDA-approved targeted therapy for neurofibromatosis type 1 (NF1), showing efficacy in treating inoperable plexiform neurofibromas, which are common and problematic tumors in NF1 patients.

Research into NF1 has advanced with better understanding of genetic and signaling pathways, leading to promising developments in combination therapies and new animal models that could enhance treatment options for other NF1-related conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neurofibromatosis in the Era of Precision Medicine: Development of MEK Inhibitors and Recent Successes with Selumetinib. Galvin, R., Watson, AL., Largaespada, DA., et al.[2022]

Selumetinib, a MEK inhibitor, has shown significant efficacy in treating plexiform neurofibromas in patients with neurofibromatosis type 1, with 68% of 50 symptomatic patients experiencing a partial response and a median tumor volume reduction of 27.9%.

The treatment demonstrated a favorable safety profile, with manageable adverse effects, and resulted in an 84% estimated progression-free survival at 3 years, marking it as the first FDA-approved therapy for inoperable plexiform neurofibromas.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Review of Selumetinib in the Treatment of Neurofibromatosis Type 1-Related Plexiform Neurofibromas. Anderson, MK., Johnson, M., Thornburg, L., et al.[2022]

In a clinical trial, the MEK inhibitor selumetinib showed promising results, inducing partial responses in 70% of children with neurofibromatosis type 1 and inoperable plexiform neurofibromas.

The treatment demonstrated a high progression-free survival rate of 84% after 3 years, indicating its potential efficacy in managing this condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Selumetinib Shrinks Tumors in Neurofibromatosis. [2021]

Selumetinib (KOSELUGO) was approved by the FDA for treating pediatric patients aged 2 and older with inoperable plexiform neurofibromas, showing a 66% overall response rate in a trial of 50 patients, with many experiencing significant symptom relief for at least 12 months.

While selumetinib is effective, it carries risks typical of MEK inhibitors, including potential ocular, cardiac, and gastrointestinal side effects, but the overall benefit-risk assessment is considered favorable for this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Selumetinib for Plexiform Neurofibroma. Casey, D., Demko, S., Sinha, A., et al.[2022]

In a phase II trial involving 19 patients with neurofibromatosis type 1 (NF1) and inoperable plexiform neurofibromas (PNs), the MAPK/ERK kinase inhibitor mirdametinib showed a 42% partial response rate after 12 courses, indicating its efficacy in reducing tumor size.

Patients reported significant and durable decreases in pain, suggesting that mirdametinib not only affects tumor volume but also improves quality of life for those suffering from NF1-related PNs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

NF106: A Neurofibromatosis Clinical Trials Consortium Phase II Trial of the MEK Inhibitor Mirdametinib (PD-0325901) in Adolescents and Adults With NF1-Related Plexiform Neurofibromas. Weiss, BD., Wolters, PL., Plotkin, SR., et al.[2022]

Citations

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pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC11825507/

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Mirdametinib (Gomekli) wins FDA approval, bringing relief ...

Mirdametinib (Gomekli) wins FDA approval, bringing relief to NF-1 patients with surgically inoperable plexiform neurofibromatosis worldwide.

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accessdata.fda.gov

accessdata.fda.gov/drugsatfda_docs/nda/2025/219379Orig1s000,219389Orig1s000RiskR.pdf

219379Orig1s000 219389Orig1s000 - accessdata.fda.gov

The FDA Clinical Team concluded that the safety profile of mirdametinib is consistent with other MEK inhibitors and is considered acceptable ...

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GOMEKLI (mirdametinib) is the FIRST AND ONLY FDA-approved treatment for both adults and children 2 years of age and older with neurofibromatosis type 1 (NF1) ...