What Is Mirdametinib?
Mirdametinib is an investigational drug that works as a highly selective and potent inhibitor of MEK1 and MEK2 kinases. These proteins are part of a signaling pathway within cells that controls growth and division. By blocking MEK1 and MEK2, mirdametinib aims to slow down or stop the uncontrolled growth of cells, which can be beneficial in treating certain cancers and other conditions involving abnormal cell proliferation. The drug is currently being investigated in clinical trials for various conditions. These include several types of cancer, such as Advanced Unresectable Melanoma, Breast Cancer, Central Nervous System Tumors, and Dedifferentiated Liposarcoma. It is also being studied for conditions like Arteriovenous Malformation, Cystic Hygroma, and Cutaneous Neurofibroma, which involve abnormal tissue development. Overall, mirdametinib has been studied in 20 clinical trials, with 12 currently recruiting participants and 3 completed. These trials have collectively enrolled a total of 849 participants, with the earliest trial starting in 2019 and the latest projected to conclude in 2026.Uses and Conditions Under Study
Mirdametinib is being investigated across a range of conditions, primarily focusing on cancers and disorders involving abnormal cell growth.- Cancers: The drug is under study for several types of cancer. This includes Advanced Unresectable Melanoma, a severe form of skin cancer that cannot be surgically removed. It is also being investigated for Breast Cancer, including Stage IV Breast Cancer, where the disease has spread. Other cancer types include Central Nervous System Tumors and Dedifferentiated Liposarcoma, a type of soft tissue cancer. As a MEK inhibitor, mirdametinib aims to disrupt the growth pathways often overactive in these malignancies. These conditions are being studied across at least 5 trials.
- Vascular and Lymphatic Malformations, and Neurofibroma: Mirdametinib is also being explored for conditions characterized by abnormal tissue development. This includes Arteriovenous Malformation (AVM) and related Arteriovenous Malformations, which are abnormal connections between arteries and veins. Cystic Hygroma, a type of lymphatic malformation, is also under investigation. Additionally, trials are studying its potential in Cutaneous Neurofibroma, benign tumors that grow on nerves under the skin. The drug's mechanism of inhibiting cell growth pathways may be beneficial in managing these conditions. These conditions are being explored in at least 4 trials.
- Healthy Participants: Mirdametinib has been studied in healthy participants in 2 trials. These studies are typically conducted to understand how the drug is processed by the body, including its absorption, distribution, metabolism, and excretion, rather than to treat a specific disease.
Dosing
Mirdametinib is administered orally, primarily in the form of capsules. The specific dosage and regimen vary significantly depending on the clinical trial and the condition being investigated. Doses studied have ranged from 2 mg to 12 mg, typically taken twice a day. One investigational regimen involves taking mirdametinib twice daily for 21 days within a 28-day cycle. Another regimen explored is 4 mg taken twice daily for 7 days per cycle. Mirdametinib has been studied both as a single agent and in combination with other therapies. For example, some trials involve its use with radiation therapy or with intravenous vinblastine chemotherapy. It has also been combined with fulvestrant in studies for breast cancer. Clinical trials have explored various dosing schedules and strengths across different patient populations, including those with specific types of glioblastoma (such as in participants with Neurofibromatosis type 1) and those with hepatic impairment. The exact dosing details are determined by the specific study protocol.Side Effects
In a clinical trial (NCT03962543) for patients with Neurofibromatosis Type 1 associated plexiform neurofibromas, all participants experienced at least one treatment-emergent adverse event. Specifically, **100%** of adult patients and **100%** of pediatric patients treated with **Mirdametinib** reported adverse events.
For a separate Phase 1 dose escalation study (NCT05580770) investigating **Mirdametinib** in combination with BGB-3245 for advanced solid tumors, the provided data indicates the incidence of treatment-emergent adverse events by participant counts across different dose cohorts. However, the specific types and frequencies of these individual adverse events are not detailed in the available results.
Clinical Trial Results
Neurofibromatosis Type 1 Associated Plexiform Neurofibromas (NCT03962543)
In a study of **Mirdametinib** for patients with Neurofibromatosis Type 1 (NF1) associated plexiform neurofibromas, significant responses were observed. The confirmed objective response rate, meaning a confirmed reduction in tumor size, was **41.4%** in adult patients and **51.8%** in pediatric patients. The average time to achieve an objective response was **9.71 months** for adults and **8.63 months** for pediatric patients.
Patients also reported improvements in key symptoms. Adults experienced a mean reduction of **1.33 units** in **pain** as measured by the Numeric Rating Scale-11 (NRS-11), while pediatric patients reported a mean reduction of **0.79 units**. Improvements in **physical function** were also noted; adult patients showed a mean increase of **2.42 T-scores** in physical function. Pediatric patients reported mean increases of **7.0 T-scores** in mobility and **11.5 T-scores** in upper extremity function, based on self-reports. Parent-proxy reports for pediatric patients also indicated improvements in physical function.
Quality of life also improved across various domains. Adult patients reported mean increases ranging from **1.51 to 5.90 units** on the Pediatric Quality of Life Inventory (PedsQL) Acute Version. Pediatric patients, through self-report and parent proxy, showed mean increases in quality of life scores ranging from **1.71 to 8.15 units**. The dispersible tablet formulation of **Mirdametinib** was found to be acceptable, with adult caregiver scores averaging **4.56 units** and pediatric cohort scores averaging **4.3 units** on the Pediatric Oral Medicine Acceptability Questionnaire (P-OMAQ).
Advanced Solid Tumors (NCT05580770)
In a Phase 1 dose escalation study evaluating **Mirdametinib** in combination with BGB-3245 for advanced solid tumors, **no objective responses** were observed in any of the dose escalation cohorts. The maximum tolerated doses identified in this study were **3 mg** and **10 mg**.
Currently Recruiting Trials
Mirdametinib is currently being investigated in a variety of clinical trials, offering potential new treatment options for patients with different conditions. These studies aim to evaluate the safety and effectiveness of mirdametinib, sometimes alone and sometimes in combination with other therapies.
- A Phase 1/2 study, NCT05937906, sponsored by Centre Georges Francois Leclerc, is evaluating chemoimmunotherapy plus a short course of mirdametinib in the first-line treatment of metastatic non-squamous non-small cell lung adenocarcinoma with PDL1 less than 50%. This study is designed to establish the recommended dose of mirdametinib. It plans to enroll 24 participants.
- The National Cancer Institute (NCI) is sponsoring a Phase 2 trial, NCT07061951, to test the effectiveness of mirdametinib in treating relapsed or refractory chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL). This trial aims to enroll 20 patients.
- Memorial Sloan Kettering Cancer Center is conducting a Phase 1/2 study, NCT07539441, to determine if mirdametinib is a safe and effective treatment for central nervous system (CNS) tumors, including glioma and neurohistiocytosis. The study targets an enrollment of 26 people.
- St. Justine's Hospital is sponsoring a Phase 1/2 study, NCT06666348, combining mirdametinib with vinblastine for newly diagnosed or previously untreated pediatric low-grade glioma (PLGG) with activation of the MAPK pathway. This study plans to enroll 50 participants.
- An Early Phase 1 "window of opportunity" trial, NCT06693284, sponsored by the University of Minnesota, is investigating mirdametinib plus vorinostat for NF1 associated, H3K27 trimethylation deficient malignant peripheral nerve sheath tumor (MPNST). This study is enrolling 8 participants.
- A Phase 2 trial, NCT07237100, led by Kevin Kim, MD, is evaluating the clinical efficacy of mirdametinib in patients with advanced NF1-mutant melanoma whose disease has progressed after previous immunotherapy. This trial aims to enroll 10 patients.
- SpringWorks Therapeutics, Inc., a healthcare company of Merck KGaA, Darmstadt, Germany, is sponsoring a Phase 1 study, NCT06997276, to understand how hepatic impairment affects the pharmacokinetics of mirdametinib. This study includes participants with moderate or severe liver impairment and healthy matched participants, with an enrollment target of 32.
- Memorial Sloan Kettering Cancer Center is also conducting a Phase 1/2 study, NCT06843967, of mirdametinib in combination with palbociclib for people with metastatic, recurrent, and unresectable liposarcoma. This study plans to enroll 54 participants.
- A Phase 2 trial, NCT05983159, sponsored by Murdoch Childrens Research Institute, is investigating targeted therapies, including mirdametinib, for patients with slow-flow or fast-flow vascular malformations driven by specific genetic variants. This study aims to enroll 50 participants.
- Johns Hopkins University is sponsoring a Phase 1/2a study, NCT06159166, of mirdametinib monotherapy in adults with Neurofibromatosis 1 (NF1) and cutaneous neurofibromas (cNF). This open-label study is designed for 24 participants.
- Children's Hospital Medical Center, Cincinnati, is conducting a Phase 2 study, NCT06153173, to evaluate mirdametinib in patients with Langerhans cell histiocytosis (LCH) or other histiocytic disorders. The study plans to enroll 40 patients.
- St. Jude Children's Research Hospital is sponsoring a Phase 1/2 study, NCT04923126, evaluating mirdametinib in children, adolescents, and young adults with low-grade glioma, including recurrent or progressive cases. This multi-center study has an enrollment target of 132 participants.
Where to Participate
Clinical trials for mirdametinib are being conducted across a broad geographic area, making participation accessible to many individuals. These studies are currently active in 26 sites across 24 cities and 13 states.
Top locations for these trials include:
- Commack, New York
- Harrison, New York
- New York, New York
- Basking Ridge, New Jersey
- Middletown, New Jersey
- Montvale, New Jersey
Eligibility for these trials generally includes participants between 2 and 80 years of age, of all genders. Some studies also include healthy volunteers, depending on the specific research goals.
Development Timeline
The development journey for mirdametinib began on April 5, 2019, with the first clinical trial. Initially, research focused on conditions such as IBS-C and hyperphosphatemia. Over time, the scope of investigation significantly broadened, reflecting the drug's potential across a diverse range of diseases.
Key sponsors like SpringWorks Therapeutics, Inc., Memorial Sloan Kettering Cancer Center, and the National Cancer Institute (NCI) have driven much of this research. The development pipeline has expanded to include various cancers and rare disorders, such as Arteriovenous Malformations, Breast Cancer, Central Nervous System Tumors, Liposarcoma, Melanoma, and different forms of Histiocytic Disorders. Mirdametinib is also being studied for Neurofibromatosis 1 (NF1) and vascular malformations, demonstrating its broad application.
To date, there have been 20 clinical trials for mirdametinib, involving a total enrollment of 849 participants. These studies have progressed through various phases, with the majority being Phase 1/2 (9 trials) and Phase 2 (6 trials), indicating ongoing evaluation of both safety and efficacy. The latest trial is projected to conclude on April 20, 2026, continuing the exploration of mirdametinib's therapeutic potential.