Neurofibromatosis Type 1-Associated Plexiform NeurofibromasPhase 1NCT07850635
A Study of Mirdametinib in Infants and Toddlers With Neurofibromatosis Type 1 Associated Plexiform Neurofibromas
A Phase 1 study testing Mirdametinib in people with Neurofibromatosis Type 1-Associated Plexiform Neurofibromas, run by SpringWorks Therapeutics, Inc., a healthcare company of Merck KGaA, Darmstadt, Germany at 1 site in Germany.
Trial summary
The purpose of this study is to determine the safety, pharmacokinetic (PK), and tolerability of multiple treatment cycles of oral mirdametinib in infants and toddlers (0 to less than [<] 24 months of age) with measurable neurofibromatosis type 1 (NF1) associated plexiform neurofibromas (PNs) that is symptomatic or… Read more about this study
- Who is it for?
- Ages 0 to 21 months
- Conditions the study is for
- Neurofibromatosis Type 1-Associated Plexiform Neurofibromas
- 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
- 6 participants
- Where
- 1 siteGermany
- Study dates
- 9 Dec 2026to 21 Oct 2032
- Phase
- Phase 1
- 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 0 to 21 months
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Age 1.1 Cohort 1: greater than (>) 12 to less than or equal to (<=) 21 months of age at first dose 1.2 Cohort 2: 0 to <=9 months of age at first dose For both cohorts, corrected age must be used to determine eligibility for age at first dose. Note: Corrected age is the age of the infant from the expected date of delivery (40 weeks gestation), rather than from the actual date of birth. For example, a 3-month-old infant who was born 2 months early would have a corrected age of 1 month.
- Participants must have had the clinical diagnosis of NF1 according to the 2021 International Consensus Guidelines with presence of a PN and at least 1 additional diagnostic criterion for NF1.
- Participants must have a target PN, defined as the clinically most relevant PN amenable to volumetric MRI analysis. For the purpose of this study, the target PN must be seen on at least 3 consecutive MRI slices and the field of view must contain the entire tumour of interest. As determined by central radiologic review, a target PN must be analysable by volumetrics using Response Evaluation in Neurofibromatosis and Schwannomatosis (REiNS), at least 3 milliliter (mL) in volume.
- Participants must have 1 of the following presentations of PN:
- 4.1. Asymptomatic: Participant has a measurable NF1 PN in a high risk location with a high risk of morbidity.
- A high-risk location with a high risk of morbidity is defined as:
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- In the head or neck (except for isolated scalp lesions) OR
- Within the brachial or lumbosacral plexus OR
- Adjacent to high-risk structure(s), defined as:
- Major ("named") blood vessel OR
- Major ("named") airway OR
- Hollow viscus OR
- Spinal cord and foramina OR
- Vital organs (including heart, lungs, liver, spleen, etc) OR 4.2. Symptomatic: Participant has a PN that is causing clinical symptoms at the discretion of the investigator (e.g., head and neck lesions compromising the airway or great vessels, brachial or lumbar plexus lesions causing nerve compression and loss of function, lesions causing major deformity or significant disfigurement, lesions of the extremity causing limb hypertrophy or loss of function, and painful lesions).
Who cannot join
- Participant has family history of sudden cardiac death.
- Participant has 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), retinal pigment epithelial detachment, or neovascular macular degeneration.
- Participant has a history of congenital glaucoma.
- Participant has received NF1 PN-targeted therapy (e.g., farnesyltransferase inhibitors, kinase inhibitors, etc) within 28 days of first dose of study treatment (or 5 half-lives, whichever is longer). All toxicities from prior therapy must resolve to Grade <=1 or baseline.
- Participant is receiving inhibitors or inducers of P-glycoprotein or breast cancer resistance protein.
- Participant is currently enrolled or has past participation in any other clinical study (excluding observational studies) within 28 days of signing of informed consent.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
About this study
Official title: A Phase 1b, Open-Label Study of Mirdametinib in Infants and Toddlers With Neurofibromatosis Type 1 Associated Plexiform Neurofibromas
The purpose of this study is to determine the safety, pharmacokinetic (PK), and tolerability of multiple treatment cycles of oral mirdametinib in infants and toddlers (0 to less than [<] 24 months of age) with measurable neurofibromatosis type 1 (NF1) associated plexiform neurofibromas (PNs) that is symptomatic or asymptomatic but in a high-risk location with a high risk of morbidity.
- Being tested
- Mirdametinib
- Keywords
- Mirdametinib, Single arm study
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MirdametinibDrug
Mirdametinib dispersible tablet administered orally.
| Study group | Role | What they receive |
|---|---|---|
| Cohort 1: 12 to 21 months of age | Experimental | Participant receives 0.5 milligram (mg) twice daily. Receives: Drug: Mirdametinib |
| Cohort 2: 0 to 9 months of age | Experimental | Participants receives 0.25 mg twice daily. Receives: Drug: Mirdametinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Treatment-emergent Adverse Events (TEAEs)
Measured: Up to approximately 6 years
Number of Participants With Clinically Significant Changes in Laboratory Parameters, Vital Signs, Physical Examination Findings and Electrocardiograms (ECGs), Echocardiogram (ECHO), and Ophthalmic Exam Findings
Measured: Up to approximately 6 years
Number of Participants With Severity of Adverse Events (AEs) According to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v5.0
Measured: Up to approximately 6 years
Minimum Observed Concentration (Cmin) of Mirdametinib
Measured: Cycle 1 Days 1 and 15: pre-dose and post-dose at 1 and 4 hours; Cycles 2, 4 and 8 Day 15: Pre-dose and post-dose at 1 hour (each cycle = 28 days)
Maximum Observed Concentration (Cmax) of Mirdametinib
Measured: Cycle 1 Days 1 and 15: pre-dose and post-dose at 1 and 4 hours; Cycles 2, 4 and 8 Day 15: Pre-dose and post-dose at 1 hour (each cycle = 28 days)
Area Under the Concentration-time Curve (AUC) at Steady State for Mirdametinib
Measured: Cycle 1 Days 1 and 15: pre-dose and post-dose at 1 and 4 hours; Cycles 2, 4 and 8 Day 15: Pre-dose and post-dose at 1 hour (each cycle = 28 days)
Secondary outcomes (4)
Confirmed Objective Response Rate (ORR)
Confirmed ORR is defined as plexiform neurofibroma (PN) decrease greater than or equal to (>=) 20 percent (%) compared to baseline in consecutive scans within 2 to 6 months) using centrally read magnetic resonance imaging (MRI) volumetric analyses by a Blinded Independent Central Review (BICR).
Measured: Up to approximately 6 years
Duration of Response (DoR)
DoR is defined as the time from onset of confirmed complete response (CR) + partial response (PR) using centrally read MRI volumetric analysis by a BICR to the earliest event of progressive disease (PD) or death.
Measured: Up to approximately 6 years
Change From Baseline in Quality of Life (QoL) Assessed by the age-specific Pediatric Quality of Life Inventory (PedsQL) Infant Scales
The PedsQL Infant Scales are multidimensional parent-proxy-report scales designed to assess health-related quality of life in infants from 1 to 24 months of age over the past 7 days. The Infant Scales consists of 36 items in the 1- to 12-month form and 45 items in the 13- to 24-month form, with 5 dimensions: physical functioning, physical symptoms, emotional functioning, social functioning, and cognitive functioning.
Measured: Baseline up to approximately 6 years
Change From Baseline Pain Assessment by Age-specific Pain Scale: Faces, Legs, Activity, Cry, Consolability (FLACC)
FLACC is a behavioural pain assessment scale used by the investigator for nonverbal or preverbal patients who are unable to self-report their level of pain. Pain is assessed in infants and children from 2 months to 7 years of age through observation of 5 categories, including face, legs, activity, cry, and consolability. The total score for FLACC scale ranges from 0 to 10, with each category scored on a scale of 0 to 2.
Measured: Baseline up to approximately 6 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Sep 2026
- Study start9 Dec 2026 (estimated)
- Primary completion21 Oct 2032 (estimated)
- Study completion21 Oct 2032 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Neurofibromatosis Type 1-Associated Plexiform NeurofibromasStudies of the same condition, open and under way.
- 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
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 6 participants (estimated)
Sponsor and investigators
- Lead sponsor
- SpringWorks Therapeutics, Inc., a healthcare company of Merck KGaA, Darmstadt, Germany
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Medical Responsible, Study director, SpringWorks Therapeutics, Inc., a healthcare company of Merck KGaA, Darmstadt, Germany
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07850635
- Sponsor's protocol ID
- MEK-NF1-104
- Other IDs
- 2025-522000-24-00, 2025
- Status last verified
- Oct 2026
- First submitted
- 24 Sep 2026
- Last updated
- 21 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: IPD will not be shared for Phase I interventional or observational studies. Further information on how to request data can be found on our website bit.ly/IPD21.
Study at a glance
From the registry record, last updated by the sponsor on 21 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1b, Open-Label Study of Mirdametinib in Infants and Toddlers With Neurofibromatosis Type 1 Associated Plexiform Neurofibromas
- ClinicalTrials.gov ID
- NCT07850635
- Acronym / sponsor ID
- MEK-NF1-104
- Keywords
- Mirdametinib, Single arm study
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 6 participants (estimated)
- Lead sponsor
- SpringWorks Therapeutics, Inc., a healthcare company of Merck KGaA, Darmstadt, GermanyIndustry (pharma, biotech, devices)
- Study start
- 9 Dec 2026 (estimated)
- Primary completion
- 21 Oct 2032 (estimated)
- Study completion
- 21 Oct 2032 (estimated)
- First posted
- 30 Sep 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 is to determine the safety, pharmacokinetic (PK), and tolerability of multiple treatment cycles of oral mirdametinib in infants and toddlers (0 to less than [<] 24 months of age) with measurable neurofibromatosis type 1 (NF1) associated plexiform neurofibromas (PNs) that is symptomatic or asymptomatic but in a high-risk location with a high risk of morbidity.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Cohort 1: 12 to 21 months of age | Experimental | Drug: MirdametinibParticipant receives 0.5 milligram (mg) twice daily. |
| Cohort 2: 0 to 9 months of age | Experimental | Drug: MirdametinibParticipants receives 0.25 mg twice daily. |
Who may qualify
- Ages
- 0 to 21 months
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (14 listed)
- Age 1.1 Cohort 1: greater than (>) 12 to less than or equal to (<=) 21 months of age at first dose 1.2 Cohort 2: 0 to <=9 months of age at first dose For both cohorts, corrected age must be used to determine eligibility for age at first dose. Note: Corrected age is the age of the infant from the expected date of delivery (40 weeks gestation), rather than from the actual date of birth. For example, a 3-month-old infant who was born 2 months early would have a corrected age of 1 month.
- Participants must have had the clinical diagnosis of NF1 according to the 2021 International Consensus Guidelines with presence of a PN and at least 1 additional diagnostic criterion for NF1.
- Participants must have a target PN, defined as the clinically most relevant PN amenable to volumetric MRI analysis. For the purpose of this study, the target PN must be seen on at least 3 consecutive MRI slices and the field of view must contain the entire tumour of interest. As determined by central radiologic review, a target PN must be analysable by volumetrics using Response Evaluation in Neurofibromatosis and Schwannomatosis (REiNS), at least 3 milliliter (mL) in volume.
- Participants must have 1 of the following presentations of PN:
- 4.1. Asymptomatic: Participant has a measurable NF1 PN in a high risk location with a high risk of morbidity.
Key exclusion criteria (6 listed)
- Participant has family history of sudden cardiac death.
- Participant has 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), retinal pigment epithelial detachment, or neovascular macular degeneration.
- Participant has a history of congenital glaucoma.
- Participant has received NF1 PN-targeted therapy (e.g., farnesyltransferase inhibitors, kinase inhibitors, etc) within 28 days of first dose of study treatment (or 5 half-lives, whichever is longer). All toxicities from prior therapy must resolve to Grade <=1 or baseline.
- Participant is receiving inhibitors or inducers of P-glycoprotein or breast cancer resistance protein.
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 dispersible tablet administered orally. | Drug | Cohort 1: 12 to 21 months of age, Cohort 2: 0 to 9 months of age |
Primary outcome
Number of Participants With Treatment-emergent Adverse Events (TEAEs)
Time frame: Up to approximately 6 years
Number of Participants With Clinically Significant Changes in Laboratory Parameters, Vital Signs, Physical Examination Findings and Electrocardiograms (ECGs), Echocardiogram (ECHO), and Ophthalmic Exam Findings
Time frame: Up to approximately 6 years
Number of Participants With Severity of Adverse Events (AEs) According to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v5.0
Time frame: Up to approximately 6 years
Minimum Observed Concentration (Cmin) of Mirdametinib
Time frame: Cycle 1 Days 1 and 15: pre-dose and post-dose at 1 and 4 hours; Cycles 2, 4 and 8 Day 15: Pre-dose and post-dose at 1 hour (each cycle = 28 days)
Maximum Observed Concentration (Cmax) of Mirdametinib
Time frame: Cycle 1 Days 1 and 15: pre-dose and post-dose at 1 and 4 hours; Cycles 2, 4 and 8 Day 15: Pre-dose and post-dose at 1 hour (each cycle = 28 days)
Area Under the Concentration-time Curve (AUC) at Steady State for Mirdametinib
Time frame: Cycle 1 Days 1 and 15: pre-dose and post-dose at 1 and 4 hours; Cycles 2, 4 and 8 Day 15: Pre-dose and post-dose at 1 hour (each cycle = 28 days)
4 secondary outcomes
Confirmed Objective Response Rate (ORR)
Time frame: Up to approximately 6 years
Duration of Response (DoR)
Time frame: Up to approximately 6 years
Change From Baseline in Quality of Life (QoL) Assessed by the age-specific Pediatric Quality of Life Inventory (PedsQL) Infant Scales
Time frame: Baseline up to approximately 6 years
Change From Baseline Pain Assessment by Age-specific Pain Scale: Faces, Legs, Activity, Cry, Consolability (FLACC)
Time frame: Baseline up to approximately 6 years
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 21 Oct 2026.
- Trial Awareness and Transparency websiteLink provided by the sponsor.
- Individual participant dataSharing planned: No. IPD will not be shared for Phase I interventional or observational studies. Further information on how to request data can be found on our website bit.ly/IPD21.
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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.
Medical Responsible study director
SpringWorks Therapeutics, Inc., a healthcare company of Merck KGaA, Darmstadt, Germany
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Mirdametinib in people with Neurofibromatosis Type 1-Associated Plexiform Neurofibromas, run by SpringWorks Therapeutics, Inc., a healthcare company of Merck KGaA, Darmstadt, Germany at 1 site in Germany.
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 14 inclusion and 6 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: opening soon, as of the sponsor's last update on 21 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Germany. 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 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.
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 Communication Center (+49 6151 72 5200, service@emdgroup.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants With Treatment-emergent Adverse Events (TEAEs) (time frame: Up to approximately 6 years). The study lists 6 primary outcomes in all. 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 21 Oct 2026.