Central Nervous System TumorsPhase 1/2NCT07539441
A Study of Mirdametinib in People With Central Nervous System Tumors
A Phase 1/2 study testing Mirdametinib in people with Central Nervous System Tumors and Glioma, run by Memorial Sloan Kettering Cancer Center at 7 sites in United States.
Trial summary
The purpose of this study to find out whether mirdametinib is a safe and effective treatment for Central Nervous System/CNS tumors (glioma and neurohistiocytosis). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Central Nervous System Tumors, Glioma
- What is being tested?
- Mirdametinib
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 26 participants
- Where
- 7 sitesUnited States
- Study dates
- 10 Apr 2026to 10 Oct 2029
- Phase
- Phase 1/2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Demographic Characteristics
- Be > 18 years of age
- General Criteria
- Have Karnofsky Performance Status (KPS) of ≥ 70% or ECOG Performance Status of ≤ 2
- Is able to understand and provide written informed consent for the trial prior to any study-specific procedures and is willing to comply with scheduled visits, treatment plans, procedures and laboratory tests. A legally authorized representative may consent on behalf of a subject who is otherwise unable to provide informed consent, if acceptable to and approved by the institutional review board.
- Medical and Therapeutic Criteria
Show all 43Show fewer
- Have adequate bone marrow function, as determined by:
- Absolute neutrophil count (ANC) >1,500/mm3
- Platelet count >100,000 mm³
- Hemoglobin >9.0 mg/dL
- Have adequate hepatic function, as determined by:
- Total bilirubin ≤1.5 x ULN if baseline was normal or ≤1.5 x baseline if baseline was abnormal. Patients with previously documented Gilbert's Syndrome may have total bilirubin ≤3 x ULN.
- AST and ALT ≤3.0 x ULN if baseline was normal or ≤3.0 x baseline if baseline was abnormal
- Have adequate renal function, as determined by:
- o Creatinine clearance (CrCL) of ≥50 mL/min by the Cockcroft-Gault formula
- CrCl (mL/min) = [140 - age (years)] x weight (kg) x 0.85 for female patients 72 creatinine (mg / dL)
- Adequate cardiac function defined as follows
- Left ventricular ejection fraction >50% as assessed by multi-gated acquisition or ultrasound or echocardiography and
- Corrected QT interval (QTc) <480 ms according to the Fridericia method (QTcF)
- Women of childbearing potential must have a negative serum pregnancy test before the start of therapy.
- Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial
- Patients previously treated with radiotherapy must have recovered from acute toxicities associated with such treatment. Toxicities of investigational therapies should have recovered to grade 1 or less before start of the trial medication.
- Additional cohort specific inclusion criteria - Neurohistiocytosis Cohort A
- Subjects must meet all of the following criteria to be enrolled in the Neurohistiocytosis cohort of this study:
- Have documented MAPK pathway mutation, or mutation not identified by tumor sequencing.: Patients with completed but negative tumor sequencing, or patients without sequencing performed but without safe disease sites for biopsy, are eligible for this study owing to the high likelihood of MAPK pathway mutation.
- Have documentation of disease: Patients must have a histologically confirmed histiocytic neoplasm or a constellation of histologic, radiologic, clinical, and/or molecular findings consistent with histiocytic neoplasm. This qualification is made because it is well known that biopsies of histiocytic neoplasms are variable and do not always demonstrate "typical" morphologic appearance with all of the classically described elements.[54] As a result, histiocytic neoplasms are not exclusively pathologic diagnoses-rather, they are interpretations of histologic findings in a clinical and radiologic context.
- Have measurable neurohistiocytic disease: Patients must have measurable radiologic or functional neurologic disease as defined by any of the following below. The presence of systemic disease is allowed however there must be at least one eligible manifestation of neurologic disease as defined below:
- Measurable disease according to modified PERCIST (mPERCIST) involving neurologic structures, i.e. meninges, brain or spinal cord parenchyma, or ocular structures (see sections below for these criteria) OR
- Measurable disease according to RECIST 1.1 involving neurologic structures OR
- Any of the below neurologic deficits referable to neurohistiocytosis amenable to longitudinal quantified assessment. The following are the allowable deficits, deemed referable to disease, with their corresponding assessments and minimum required abnormalities:
- Dysarthria as defined Speech Intelligibility of B or worse as measured by the Frenchay Dysarthria Scale
- Ataxia as defined by a score of 3 or higher on the Scale for assessment and rating of ataxia (SARA)
- Diplopia as defined by Prism Diopter of 5 or higher
- Loss of visual acuity defined as best corrected visual acuity (BCVA) 20/40 (0.3 LogMAR) or worse in either eye
- Diminished visual field, defined as 20% or higher deficit in Humphrey Visual Field 24-2 pattern deviation.
- Additional cohort specific inclusion criteria - Glioma Cohort B
- Subjects must meet all of the following criteria to be enrolled in the glioma cohort of this study:
- Have: somatic NF1 mutation as per next-generation sequencing (such as MSK Impact) --or- germline NF1 as per NIH clinical criteria
- Have a histologically confirmed glioma (per the 2021 WHO Classification of Tumors of the central nervous system)
- Have measurable, MRI-evaluable, unequivocal contrast enhancing disease as determined by radiologist on T1 post-contrast weighted images. Per RANO criteria, measurable lesion is defined as at least 1 enhancing lesion measuring > 1 cm x > 1 cm
- Have recurrent or progressive disease and received prior treatment with chemotherapy, radiation, or both
- Surgical resection is indicated for treatment, but surgery is not urgently indicated (e.g. for whom surgery within the next 4-6 weeks is appropriate)
- Have expected survival of > 3 months
Who cannot join
- Subjects who meet any of the following criteria will not be enrolled in the study:
- General criteria
- Is pregnant or nursing
- Is participating in another interventional study at the same time; participation in non-therapeutic registries is allowed
- Medical and Therapeutic criteria
- Receipt of tumor directed therapy (chemotherapy, targeted therapy, biologic, investigational) within 28 days or 5 half-lives (whichever is shorter) before the first dose of mirdametinib.
Show all 19Show fewer
- Concomitant use of medications that strongly induce CYP3A
- History of allergic reaction to the study agent(s), compounds of similar chemical or biologic composition to the study agent (s) (or any of its excipients).
- Evidence of serious active infections. Patients are allowed to enroll if they have been fever free for at least 48 hours
- Uncontrolled or severe intercurrent medical condition
- Have significant active cardiac disease within 6 months before the start of treatment, including New York Heart Association Class III or IV congestive heart failure, atrial fibrillation, myocardial infarction, unstable angina and/or stroke.
- Have significant active ophthalmologic disease within 6 months before the start of treatment, including central retinal vein occlusion
- Has a history of or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the subject's participation for the full duration of the study, or is not in the best interest of the subject to participate, in the opinion of the treating Investigator
- Cohort A only: Patients with documented driver mutations outside of the MAPK pathway are not eligible for this study. These are uncommon and include mutations in ALK, RET, CSF1R, NTRK, and other kinases20 .
- On Study Guidelines:
- Physicians should consider the following when evaluating if the patient is appropriate for this study:
- Cohorts A and B: Patients with cytopenias, renal impairment or hepatic impairment deemed the direct result of disease and therefore amenable to improvement with mirdametinib treatment may be enrolled at the discretion of the treating investigator
- Cohort A: There is no prior therapy requirement given the poor CNS efficacy of standard therapies, morbidity of neurohistiocytosis, and the available data about safety and efficacy in nine patients treated with mirdametinib.
- The effects of mirdametinib on the developing human fetus are unknown. For this reason, female participants of child-bearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) during study therapy and for 6 weeks following the completion of study therapy. Male participants with female partners of reproductive potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) during study therapy and for 3 months following the completion of study therapy. Should a participant become pregnant or suspect pregnancy while participating in this study, they should inform their treating physician immediately.
Trial locations and contacts
7 sites in 1 country. Contact the study team or a site near you to ask about taking part.
7 sites in 1 country
United States7 sites, 7 recruiting
- Recruiting
Memorial Sloan Kettering Basking Ridge (Limited Protocol Activities)
Basking Ridge, New Jersey, 07920
Anna Piotrowski, MD, 212-610-0483
- Recruiting
Memorial Sloan Kettering Suffolk - Commack (Limited Protocol Activities)
Commack, New York, 11725
Anna Piotrowski, MD, 212-610-0483
- Recruiting
Memorial Sloan Kettering Westchester (Limited Protocol Activities)
Harrison, New York, 10604
Anna Piotrowski, MD, 212-610-0483
- Recruiting
Memorial Sloan Kettering Monmouth (Limited protocol activities)
Middletown, New Jersey, 07748
Anna Piotrowski, MD, 212-610-0483
- Recruiting
Memorial Sloan Kettering Bergen (Limited Protocol Activities)
Montvale, New Jersey, 07645
Anna Piotrowski, MD, 212-610-0483
- Recruiting
Memorial Sloan Kettering Cancer Center (All Protocol Activities)
New York, New York, 10065
Anna Piotrowski, MD, 212-610-0483
- Recruiting
Memorial Sloan Kettering Nassau (Limited Protocol Activities)
Rockville Centre, New York, 11570
Anna Piotrowski, MD, 212-610-0483
About this study
Official title: Phase 1/2 Trial of Mirdametinib in Patients With MAPK Pathway Mutant Central Nervous System Tumors
The purpose of this study to find out whether mirdametinib is a safe and effective treatment for Central Nervous System/CNS tumors (glioma and neurohistiocytosis).
- Conditions
- Central Nervous System Tumors, Glioma
- Being tested
- Mirdametinib
- Keywords
- Central Nervous System Tumors, Glioma, Neurohistiocytosis, Mirdametinib, Memorial Sloan Kettering Cancer Center, 26-103
- Medical subject headings
- Central Nervous System Neoplasms, Glioma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MirdametinibDrug
Mirdametinib is a highly selective and potent, non-ATP-competitive oral inhibitor of MEK1 and MEK2 kinases
| Study group | Role | What they receive |
|---|---|---|
| Cohort A: Mirdametinib | Experimental | 11 participants with refractory neurohistiocytosis will be treated with mirdametinib in continuous treatment cycles Receives: Drug: Mirdametinib |
| Cohort B: Perioperative mirdametinib | Experimental | 15 participants with recurrent NF1-mutant glioma will be randomized in a 2:1 ratio to receive either perioperative mirdametinib (for 5 days) or no drug before standard of care surgery. All 15 participants will be treated with mirdametinib twice daily after surgery, continuously until clinical or radiographic progression of disease Receives: Drug: Mirdametinib |
| Cohort B: No perioperative mirdametinib | No intervention | 15 participants with recurrent NF1-mutant glioma will be randomized in a 2:1 ratio to receive either perioperative mirdametinib (for 5 days) or no drug before standard of care surgery. All 15 participants will be treated with mirdametinib twice daily after surgery, continuously until clinical or radiographic progression of disease |
What is being measured
The primary outcome is the main question the study is designed to answer.
Best overall neurologic response rate
To determine the best overall neurologic response rate
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Apr 2026
- Study start10 Apr 2026
- Primary completion10 Oct 2029 (estimated)
- Study completion10 Oct 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Central Nervous System TumorsStudies of the same condition, open and under way.
- More trials run by Memorial Sloan Kettering Cancer CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 26 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Memorial Sloan Kettering Cancer Center
- Sponsor type
- University, hospital or other
- Collaborators
- Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany
- Responsible party
- Sponsor
- Investigators
- Anna Piotrowski, MD, Principal investigator, Memorial Sloan Kettering Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07539441
- Sponsor's protocol ID
- 26-103
- Status last verified
- Sep 2026
- First submitted
- 13 Apr 2026
- Last updated
- 3 Sep 2026
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Memorial Sloan Kettering Cancer Center supports the international committee of medical journal editors (ICMJE) and the ethical obligation of responsible sharing of data from clinical trials. The protocol summary, a statistical summary, and informed consent form will be made available on clinicaltrials.gov when required as a condition of Federal awards, other agreements supporting the research and/or as otherwise required. Requests for deidentified individual participant data can be made following one year after publication and for up to 36 months later. Deidentified individual participant data reported in the manuscript will be shared under the terms of a Data Use Agreement and may only be used for approved proposals. Requests may be made to: crdatashare@mskcc.org.
Study at a glance
From the registry record, last updated by the sponsor on 3 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase 1/2 Trial of Mirdametinib in Patients With MAPK Pathway Mutant Central Nervous System Tumors
- ClinicalTrials.gov ID
- NCT07539441
- Acronym / sponsor ID
- 26-103
- Conditions
- Central Nervous System Tumors, Glioma
- Keywords
- Central Nervous System Tumors, Glioma, Neurohistiocytosis, Mirdametinib, Memorial Sloan Kettering Cancer Center, 26-103
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 26 participants (estimated)
- Lead sponsor
- Memorial Sloan Kettering Cancer CenterUniversity, hospital or other
- Collaborators
- Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany
- Study start
- 10 Apr 2026 (actual)
- Primary completion
- 10 Oct 2029 (estimated)
- Study completion
- 10 Oct 2029 (estimated)
- First posted
- 20 Apr 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study to find out whether mirdametinib is a safe and effective treatment for Central Nervous System/CNS tumors (glioma and neurohistiocytosis).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Cohort A: Mirdametinib | Experimental | Drug: Mirdametinib11 participants with refractory neurohistiocytosis will be treated with mirdametinib in continuous treatment cycles |
| Cohort B: Perioperative mirdametinib | Experimental | Drug: Mirdametinib15 participants with recurrent NF1-mutant glioma will be randomized in a 2:1 ratio to receive either perioperative mirdametinib (for 5 days) or no drug before standard of care surgery. All 15 participants will be treated with mirdametinib twice daily after surgery, continuously until clinical or radiographic progression of disease |
| Cohort B: No perioperative mirdametinib | No intervention | –15 participants with recurrent NF1-mutant glioma will be randomized in a 2:1 ratio to receive either perioperative mirdametinib (for 5 days) or no drug before standard of care surgery. All 15 participants will be treated with mirdametinib twice daily after surgery, continuously until clinical or radiographic progression of disease |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (43 listed)
- Demographic Characteristics
- Be > 18 years of age
- General Criteria
- Have Karnofsky Performance Status (KPS) of ≥ 70% or ECOG Performance Status of ≤ 2
- Is able to understand and provide written informed consent for the trial prior to any study-specific procedures and is willing to comply with scheduled visits, treatment plans, procedures and laboratory tests. A legally authorized representative may consent on behalf of a subject who is otherwise unable to provide informed consent, if acceptable to and approved by the institutional review board.
Key exclusion criteria (19 listed)
- General criteria
- Is pregnant or nursing
- Is participating in another interventional study at the same time; participation in non-therapeutic registries is allowed
- Medical and Therapeutic criteria
- Receipt of tumor directed therapy (chemotherapy, targeted therapy, biologic, investigational) within 28 days or 5 half-lives (whichever is shorter) before the first dose of mirdametinib.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MirdametinibMirdametinib is a highly selective and potent, non-ATP-competitive oral inhibitor of MEK1 and MEK2 kinases | Drug | Cohort A: Mirdametinib, Cohort B: Perioperative mirdametinib |
Primary outcome
Best overall neurologic response rate
Time frame: 1 year
To determine the best overall neurologic response rate
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Sep 2026.
- Memorial Sloan Kettering Cancer CenterLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. Memorial Sloan Kettering Cancer Center supports the international committee of medical journal editors (ICMJE) and the ethical obligation of responsible sharing of data from clinical trials. The protocol summary, a statistical summary, and informed consent form will be made available on clinicaltrials.gov when required as a condition of Federal awards, other agreements supporting the research and/or as otherwise required. Requests for deidentified individual participant data can be made following one year after publication and for up to 36 months later. Deidentified individual participant data reported in the manuscript will be shared under the terms of a Data Use Agreement and may only be used for approved proposals. Requests may be made to: crdatashare@mskcc.org.
Related trials for Central Nervous System Tumors
RecruitingPhase 2
Ibrutinib Combination Therapy in Transplant Ineligible Individuals With Newly Diagnosed Primary CNS Lymphoma
Non-hodgkin Lymphoma
RecruitingPhase 2
BrAin Metastasis in tripLe Negateive Breast Cancer: IvoneScimab and Trop2 ADC
Triple-Negative Breast Cancer (TNBC), Brain Metastases
Active, not recruiting
Effects of Whole-body Electrical Muscle Stimulation Exercise on Adults With Neuromuscular Disease
Neuromuscular Diseases (NMD), Amyotrophic Lateral Sclerosis
Active, not recruitingPhase 1
Prospective Exploratory Study of FAPi PET/CT With Histopathology Validation in Patients With Various Cancers
Bladder Carcinoma, Cervical Carcinoma
RecruitingPhase 1/2
PLX038 in Primary Central Nervous System Tumors Containing MYC or MYCN Amplifications
Glioma, Medulloblastoma
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Anna Piotrowski, MD principal investigator
Memorial Sloan Kettering Cancer Center
7 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Mirdametinib in people with Central Nervous System Tumors and Glioma, run by Memorial Sloan Kettering Cancer Center at 7 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 43 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 3 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 7 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Anna Piotrowski, MD (212-610-0483, piotrowa@mskcc.org), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Best overall neurologic response rate (time frame: 1 year). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Sep 2026.