MIRDAMETINIB for Neurofibromatosis type 1 associated plexiform neurofibroma

Inclusion criteria

• {"criterion_text":"-Age 1.1.\tCohort 1: ≥12 to ≤21 months of age at first dose 1.2.\tCohort 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."}
• {"criterion_text":"-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"}
• {"criterion_text":"-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 REiNS, at least 3 mL in volume."}
• {"criterion_text":"-Participants must have 1 of the following presentations of PN: 4.1. Asymptomatic: Participant has a target 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: • In the head or neck (except for isolated scalp lesions) OR • Within the brachial or lumbosacral plexus OR •\tAdjacent to high-risk structure(s), defined as: o Major (“named”) blood vessel OR o Major (“named”) airway OR o Hollow viscus OR o Spinal cord and foramina OR o Vital organs (including heart, lungs, liver, spleen, etc) OR 4.2.\tSymptomatic: 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)."}

Exclusion criteria

• {"criterion_text":"-Participant has family history of sudden cardiac death"}
• {"criterion_text":"-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"}
• {"criterion_text":"-Participant has a history of congenital glaucoma"}
• {"criterion_text":"-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."}
• {"criterion_text":"-Participant is receiving inhibitors or inducers of P-glycoprotein or breast cancer resistance protein"}
• {"criterion_text":"-Participant is currently enrolled or has past participation in any other clinical study (excluding observational studies) within 28 days of signing of informed consent"}

Primary endpoints

• {"endpoint_text":"-Key safety endpoints will include incidence of TEAEs, changes in laboratory parameters, vital signs, physical examination findings and electrocardiograms (ECGs), echocardiogram (ECHO), and ophthalmic exam findings","definition_or_measurement_approach":"Safety assessed by incidence of treatment-emergent adverse events (TEAEs), changes in labs, vital signs, physical exams, ECG, ECHO, and ophthalmic examinations."}
• {"endpoint_text":"-The severity of all AEs will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v5.0.","definition_or_measurement_approach":"AE severity graded per NCI CTCAE v5.0."}
• {"endpoint_text":"-PK parameters, such as Cmin, Cmax, and AUC at steady state.","definition_or_measurement_approach":"Pharmacokinetic parameters measured including Cmin, Cmax, and AUC at steady state."}

Secondary endpoints

• {"endpoint_text":"-Confirmed ORR (defined as PN decrease ≥20% compared to baseline in consecutive scans within 2 to 6 months) using centrally read MRI volumetric analyses by a Blinded Independent Central Review (BICR).","definition_or_measurement_approach":"Confirmed objective response rate (ORR) defined as ≥20% decrease in PN volume vs baseline on consecutive centrally read volumetric MRI scans within 2–6 months (BICR)."}
• {"endpoint_text":"-DoR, 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.","definition_or_measurement_approach":"Duration of response measured from onset of confirmed CR/PR (centrally read volumetric MRI by BICR) to earliest PD or death."}
• {"endpoint_text":"-Change from baseline in QoL assessed by the age-specific Paediatric Quality of Life Inventory (PedsQL) Infant Scales.","definition_or_measurement_approach":"Quality of life changes measured by age-specific PedsQL Infant Scales (parent proxy-reported)."}
• {"endpoint_text":"-Change from baseline pain assessment by age-specific pain scale: faces, legs, activity, cry, consolability (FLACC)","definition_or_measurement_approach":"Pain assessed by age-appropriate FLACC scale; change from baseline reported."}

Spain

Earliest CTIS Part Ii Submission Date

11-11-2025

Latest Decision Or Authorization Date

27-11-2025

Processing Time Days

16

Number Of Sites

2

Number Of Participants

4

Germany

Earliest CTIS Part Ii Submission Date

29-09-2025

Latest Decision Or Authorization Date

19-12-2025

Processing Time Days

81

Number Of Sites

2

Number Of Participants

4

Primary sponsor

Full Name

Springworks Therapeutics Inc.

Organisation Type

Pharmaceutical company

Country Of Registered Address

United States

Contract research organisations

Name

Advanced Clinical LLC

Responsibilities

Full service CRO (sponsor duties entries include: [{"id":874537,"code":"15","value":"Full service CRO"}])

Third parties

• {"country":"United States","full_name":"Medidata Solutions Inc.","duties_or_roles":"[{\"id\":874543,\"code\":\"7\"}]","organisation_type":"Non-Pharmaceutical company"}
• {"country":"Germany","full_name":"PCI Pharma Services Germany GmbH","duties_or_roles":"[{\"id\":874546,\"code\":\"15\",\"value\":\"Study treatment storage, distribution\"}]","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Radmd LLC","duties_or_roles":"[{\"id\":874547,\"code\":\"15\",\"value\":\"Central Imaging\"}]","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"United States","full_name":"Q Squared Solutions LLC","duties_or_roles":"[{\"id\":874549,\"code\":\"4\"}]","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"United States","full_name":"Andersonbrecon Inc.","duties_or_roles":"[{\"id\":874541,\"code\":\"15\",\"value\":\"Study treatment labeling\"}]","organisation_type":"Pharmaceutical company"}
• {"country":"Ireland","full_name":"Millmount Healthcare Limited","duties_or_roles":"[{\"id\":874542,\"code\":\"15\",\"value\":\"Study treatment QP Release\"}]","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Block Clinical Inc.","duties_or_roles":"[{\"id\":874540,\"code\":\"15\",\"value\":\"Investigator grant payment and participant reimbursement & travel assistance\"}]","organisation_type":"Non-Pharmaceutical company"}
• {"country":"United States","full_name":"Supera Fulfillment LLC","duties_or_roles":"[{\"id\":874544,\"code\":\"15\",\"value\":\"Central lab supplies\"}]","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"4g Clinical LLC","duties_or_roles":"[{\"id\":874545,\"code\":\"3\"}]","organisation_type":"Non-Pharmaceutical company"}
• {"country":"United States","full_name":"Advanced Clinical LLC","duties_or_roles":"[{\"id\":874535,\"code\":\"1\"},{\"id\":874536,\"code\":\"12\"},{\"id\":874537,\"code\":\"15\",\"value\":\"Full service CRO\"},{\"id\":874538,\"code\":\"5\"},{\"id\":874539,\"code\":\"8\"}]","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"United Biosource LLC","duties_or_roles":"[{\"id\":874548,\"code\":\"15\",\"value\":\"Pharmacovigilance\"}]","organisation_type":"Pharmaceutical company"}