A Phase 2 interventional study of Mirdametinib (PD-0325901) oral capsule or dispersible tablet in Plexiform Neurofibroma and Neurofibromatosis Type 1 (NF1), sponsored by SpringWorks Therapeutics, Inc., a healthcare company of Merck KGaA, Darmstadt, Germany. Active, not recruiting at 43 sites in United States. Open to participants aged 2 Years and older. Per ClinicalTrials.gov, last updated 2026-10-06.
Sponsored by SpringWorks Therapeutics, Inc., a healthcare company of Merck KGaA, Darmstadt, Germany (part of Merck KGaA, Darmstadt, Germany) · Phase 2, Interventional, and Treatment
This study evaluates mirdametinib (PD-0325901) in the treatment of symptomatic inoperable neurofibromatosis type-1 (NF1)-associated plexiform neurofibromas (PNs). All participants will receive mirdametinib (PD-0325901). Eligible participants may continue in a long-term follow-up phase.
Neurofibromas are non-malignant peripheral nerve sheath tumors, which are classified as plexiform neurofibromas (PNs) if they extend longitudinally along a nerve and involve multiple fascicles. PNs are a major cause of morbidity and disfigurement in individuals with NF1, and as the tumor growth progresses, can cause a multitude of clinical problems including pain and impaired physical function. PNs have the potential to undergo malignant transformation to Malignant Peripheral Nerve Sheet Tumors (MPNST).
Mirdametinib (PD-0325901) is an orally delivered, highly selective small-molecule inhibitor of the dual specificity kinases, MEK1 and MEK2 (MAPK/ERK Kinase) which prevents the phosphorylation and subsequent activation of mitogen-activated protein kinase (MAPK).
Previous studies of mirdametinib (PD-0325901) demonstrated PN shrinkage and sustained inhibition of pERK. Reduced tumor volume indicated that cell proliferation or cell death may be altered in PNs with administration of mirdametinib (PD-0325901).
63 studies on the registry are indexed under Neurofibroma, Plexiform; 19 are open to participants now.
This study's enrollment of 114 is above the median of 36 across 43 interventional studies indexed under Neurofibroma, Plexiform.
Browse Neurofibroma, Plexiform studies →SpringWorks Therapeutics, Inc., a healthcare company of Merck KGaA, Darmstadt, Germany is the lead sponsor of 14 studies on the registry; 6 are open to participants now.
Of its 5 completed or terminated interventional studies of FDA-regulated products, 3 (60%) have results posted.
First submitted before SpringWorks Therapeutics, Inc. became part of Merck KGaA, Darmstadt, Germany.
Counted across the registry records on this site, refreshed daily.
Key Inclusion Criteria:
Key Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
A biopsy takes a small piece of tissue to examine. “Archival tissue” is a sample already taken, for example at diagnosis, and kept by the hospital.
Whether a stored sample will do depends on when it was taken, how much there is and what the study needs. Ask whether the study accepts your stored sample or needs a new biopsy.
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
Cancer that has spread from where it began to other parts of the body. “Metastatic” cancer is cancer that has spread this way.
On an ECG, the QT interval is the time the heart’s lower chambers take to activate electrically and recover in each beat. QTc is that time adjusted for heart rate (QTcF by Fridericia’s formula, QTcB by Bazett’s). Some medicines lengthen it, and a long QTc can raise the risk of a dangerous heart rhythm.
The study may name a correction formula and a limit in milliseconds, often around 450–480.
Biopsy and archival tissue
A biopsy takes a small piece of tissue to examine. “Archival tissue” is a sample already taken, for example at diagnosis, and kept by the hospital.
Whether a stored sample will do depends on when it was taken, how much there is and what the study needs. Ask whether the study accepts your stored sample or needs a new biopsy.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Cancer (malignancy)
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Metastases
Cancer that has spread from where it began to other parts of the body. “Metastatic” cancer is cancer that has spread this way.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
QT and QTc
On an ECG, the QT interval is the time the heart’s lower chambers take to activate electrically and recover in each beat. QTc is that time adjusted for heart rate (QTcF by Fridericia’s formula, QTcB by Bazett’s). Some medicines lengthen it, and a long QTc can raise the risk of a dangerous heart rhythm.
The study may name a correction formula and a limit in milliseconds, often around 450–480.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Mirdametinib (PD-0325901) capsule or dispersible tablet 2 mg/m\^2 (maximum dose of 4 mg) by mouth twice daily
Drug: Mirdametinib (PD-0325901) oral capsule or dispersible tablet
Mirdametinib (PD-0325901) capsule or dispersible tablet
Also known as: PD-0325901, Mirdametinib
Confirmed Objective Response Rate at the End of the Treatment Phase.
Response will be determined by a blinded centralized review of volumetric MRI. The confirmed objective response rate (complete or partial response) by the end of Treatment Phase (i.e., Cycle 24) is defined as the proportion of participants who have a confirmed ≥ 20% reduction in target tumor volume as compared to baseline as assessed by a BICR, and the response needs to be confirmed by BICR in a consecutive tumor assessment within 2 - 6 months. Partial response is defined as a ≥ 20% reduction in target tumor volume from baseline. Complete response is defined as the complete resolution of the target tumor.
Time frame: Up to 24 months
Percentage of Patients With Treatment-Emergent Adverse Events.
All adverse events were coded using MedDRA Version 24.0. Adverse events will be assessed according to toxicities graded by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0.
Time frame: All SAEs and AEs were collected from the time of signing ICF until 30 days after the last dose of study treatment, an average of 1 year and 10 months and up to 3 years and 10 months.
Duration of Response (DOR) for Participants Who Meet Criteria for Confirmed Objective Response.
Duration of response is defined as the time in months between the first instance of response that is subsequently confirmed, until the date of radiographic disease progression or death, whichever occurs first. For participants who enter the LTFU Phase, all MRI assessments in both the Treatment Phase and LTFU Phase will be used to determine duration of response. Participants without radiographic disease progression or death while on study will have their results censored to their most recent adequate (i.e. evaluable) tumor assessment date.
Time frame: Starting on the onset of confirmed objective response in the Treatment Phase and afterwards on the 15th day of every 4 cycles (each cycle is 28 days) until disease progression or death, whichever comes first, assessed up to approximately 3 years
Change From Baseline on Quality of Life (QOL) as Measured by the Pediatric Quality of Life Inventory (PedsQL) at Cycle 13, Acute Version.
The PedsQL consists of a 23-item core measure of global QOL that can be completed in approximately 5 minutes. There is a total score and four subscales: physical functioning, emotional functioning, social functioning and school/work functioning. Participants ≥ 5 years of age complete an age-appropriate self-report; and parents/guardians of children ages 2-17 complete a parent proxy report of the age-specific QOL. The recall period is 7 days. PedsQL items are answered on a Likert scale with responses ranging from 0 to 4 (where 0 means it is never a problem and 4 means it is almost always a problem). These items are then reverse scored and linearly transformed to a 0-100 scale as follows: 0=100, 1=75, 2=50, 3=25, 4=0. On this scale, higher scores indicate better outcomes. Overall scale scores are calculated as the mean of the scores for the questions in said scale (or of all questions for the total score). The change from baseline is modelled using a mixed-model for repeated measures.
Time frame: Baseline and Cycle 13 (1 cycle = 28 days), up to 12 months
Change From Baseline in Pain as Measured by the Numeric Rating Scale-11 (NRS-11) at Cycle 13.
The NRS-11 is a self-reported 11-point numerical scale that assesses pain severity. Participants ≥ 8 years of age are asked to select a number from 0 (no pain) to 10 (worst pain you can imagine) that best describes their worst pain. The recall period is 24 hours. The change from baseline is modelled using a mixed-model for repeated measures.
Time frame: Baseline and Cycle 13 (1 cycle = 28 days), up to 12 months
Change From Baseline in Pain as Measured by the Pain Interference Index (PII) at Cycle 13.
The PII assesses relevant aspects of one's life, including pain interference with activities, spending time with family/friends, mood, sleep and attention. Participants ≥ 6 years of age complete a self-report, and parents/guardians of children aged 6-17 complete a parent proxy report. The recall period is 24 hours. The PII consists of 6 questions, each asking the responder to select one number from 0 to 6 that best describes how their/their proxy's pain has impacted various items over the past 24 hours with 0 representing "Not at all" and 6 representing "Completely". The mean of the completed items is taken as the PII score for a single assessment. The PII score presented each visit will be taken as the average of the PII scores over the 7 consecutive days up to and including visit day, with no transformation applied. The change from baseline is modelled using a mixed-model for repeated measures.
Time frame: Baseline and Cycle 13 (1 cycle = 28 days), up to 12 months
Change From Baseline in Localized Strength (Dynamometer) at Cycle 13.
Assessment of strength will be conducted only in the area affected by the target tumor. Measurements will be obtained using Medical Research Council (MRC) grading followed by quantitative assessments using the sponsor provided MicroFET2 dynamometer. Dynamometer assessment (in lbs) must be conducted in accordance with the study reference manual. For each participant, the sum of the dynamometer scores for the muscle groups tested will be taken as an overall score for each visit with higher scores indicating better localized strength. To assess the change from baseline at a visit, a participant will need assessments in which all the following categories, as assessed at baseline, match at that visit: side affected, position during assessment (sitting/supine/lateral decubitus), muscle group assessed. The change from baseline in localized strength measured by the sum of the dynamometer scores for the muscle groups tested will be assessed at Cycle 13.
Time frame: Baseline and Cycle 13 (1 cycle = 28 days), up to 12 months
Change From Baseline in Range of Motion of PN-Associated Functional Impairment at Cycle 13.
If motor dysfunction or weakness is evident, range of motion of the affected areas and/or joints will be measured by a goniometer.
Time frame: Baseline and Cycle 13 (1 cycle = 28 days), up to 12 months
Change From Baseline in Endurance at Cycle 13.
If airway or lower extremity motor dysfunction is evident, endurance will be measured by completion of a 6-minute walking test.
Time frame: Baseline and Cycle 13 (1 cycle = 28 days), up to 12 months
Time to Response Defined as the Time Between First Dose and the First Date of Objective Response That is Subsequently Confirmed.
Response will be determined by a blinded centralized review of volumetric MRI. Time to response is defined as the time in months from the start of treatment to the date of first response that was subsequently confirmed.
Time frame: Up to 24 months
Time to Progression, From the First Dose to the First Date of a ≥ 20% Increase in Tumor Volume From Baseline.
Evidence of progression or tumor growth will be determined by a blinded centralized review of volumetric MRI. Time to progression is defined as the time in months between the first treatment date until the date of radiographic disease progression. For participants who enter the LTFU Phase, all MRI assessments in both the Treatment Phase and LTFU Phase will be used to determine time to progression. Participants without radiographic disease progression will have their results censored to their most recent adequate (i.e. evaluable) tumor assessment date.
Time frame: On the 15th day of every 4 cycles (each cycle is 28 days) until disease progression is observed, assessed up to approximately 3.5 years
Progression Free Survival, Defined as the Time in Months From the First Dose to the Date of the First ≥ 20% Increase in Tumor Volume From Baseline or Death.
Evidence of progression or tumor growth will be determined by a blinded centralized review of volumetric MRI. Progression free survival is defined as the time in months between the first treatment date, until the date of radiographic disease progression or death, whichever occurs first. For participants who enter the LTFU Phase, all MRI assessments in both the Treatment Phase and LTFU Phase will be used to determine progression free survival. Participants without radiographic disease progression or death while on study will have their results censored to their most recent adequate (i.e. evaluable) tumor assessment date.
Time frame: On the 15th day of every 4 cycles (each cycle is 28 days) until disease progression is observed or death, whichever comes first, assessed up to approximately 3.5 years
Change From Baseline in PN-Associated Disfigurement Using Standardized Photography, Centrally Reviewed.
For participants with a PN that is visible and amenable to photography, changes in visible tumor aspects will be evaluated by a centralized reviewer.
Time frame: Up to 24 months
Comparison of Tumor Response to Levels of pERK and Biomarkers Indicative of Inhibition of Downstream Targets of MEK (eg, ERK Phosphorylation).
Measured in tumor biopsies in participants ≥ 18 years of age.
Time frame: Up to 24 months
Acceptability of the Dispersible Tablet Formulation as Measured by the Pediatric Oral Medicine Acceptability Questionnaire (P-OMAQ)
The Pediatric Oral Medicine Acceptability Questionnaire (P-OMAQ) uses a 5-point numerical rate scale to measure acceptability of use of the tablet formulation with questions related to taste, smell and administration of study medication. Participants ≥ 8 years of age complete a 12-item self-report; adult parents/caregivers responsible for oversight of study drug administration for participants ages 6 months to 17 years complete a 19-item caregiver report. Each questionnaire is provided with a "past 7 days" recall with all items using a 5-point Numerical Rate Scale (1 to 5) with higher item-scores reflecting greater oral treatment acceptability. The overall P-OMAQ-P (pediatric self-report) and P-OMAQ-C (adult caregiver) scores for a participant in the study will be taken as the mean of all answered questions on the respective questionnaire.
Time frame: Completed only once through study completion
Change From Baseline in Localized Strength (Medical Research Council (MRC) Scale Grading) at Cycle 13.
If motor dysfunction or weakness is evident, strength of the affected muscle groups will be measured by dynamometer and assessed by a muscle grading scale. Medical Research Council (MRC) Scale grading (0-5) must be conducted in accordance with the study reference manual. MRC Grading is assessed on a scale of 0 to 5, with 0 representing no movement being observed, and 5 representing the muscle contracting normally against full resistance. To assess the change from baseline at a visit, a participant will need assessments in which all the following categories, as assessed at baseline, match at that visit: side affected, position during assessment (sitting/supine/lateral decubitus), muscle group assessed. The MRC Grade visit score is calculated for each participant separately, and these scores are then averaged.
Time frame: Baseline and Cycle 13 (1 cycle = 28 days), up to 12 months
Change From Baseline in Physical Function Status as Measured by the Patient-Reported Outcomes Measurement Information System (PROMIS) at Cycle 13: Pediatric v2.0 Mobility 8a.
PROMIS measures capability of physical functioning, with questions related to daily activities. Participants 8-17 years complete a self-report of physical function in the upper extremity or lower extremity (mobility), depending on the location of the PN. The recall period is 7 days. All PROMIS items are answered on a Likert scale with responses ranging from 1 to 5, with higher scores representing higher reported mobility. The total raw score will be calculated as the sum of the individual item responses at a given visit (total raw scale range 8-40). The total raw scores for the measure will be converted to T-scores using the applicable score conversion table in the user manual and scoring instructions (PROMIS, 2023) ranging from 14 to 59 for self-report, and 14 to 56 for parent proxy with higher scores representing higher reported mobility and better outcomes. A T-score of 50 indicates the population mean with a standard deviation of 10.
Time frame: Baseline and Cycle 13 (1 cycle = 28 days), up to 12 months
Change From Baseline in Physical Function Status as Measured by the Patient-Reported Outcomes Measurement Information System (PROMIS) at Cycle 13: Pediatric v2.0 Upper Extremities 8a.
PROMIS measures capability of physical functioning, with questions related to daily activities. Participants 8-17 years complete a self-report of physical function in the upper extremity or lower extremity (mobility), depending on the location of the PN. The recall period is 7 days. All PROMIS items are answered on a Likert scale with responses ranging from 1 to 5, with higher scores representing higher physical functioning in the upper extremities. The total raw score will be calculated as the sum of the individual item responses at a given visit (total raw scale range 8-40). The total raw scores for the measure will be converted to T-scores using the applicable score conversion table in the user manual and scoring instructions (PROMIS, 2023) ranging from 10 to 57 for self-report, and 13 to 55 for parent proxy with higher scores representing higher reported physical functioning and better outcomes. A T-score of 50 indicates the population mean with a standard deviation of 10.
Time frame: Baseline and Cycle 13 (1 cycle = 28 days), up to 12 months
Change From Baseline in Physical Function Status as Measured by the Patient-Reported Outcomes Measurement Information System (PROMIS) at Cycle 13: Adult v2.0 Physical Function 8b.
PROMIS measures capability of physical functioning, with questions related to daily activities. Participants ≥ 18 years with a target PN impacting physical functioning complete a self-report of physical function. The recall period is 7 days. All PROMIS items are answered on a Likert scale with responses ranging from 1 to 5, with higher scores representing higher reported physical capability. The total raw score will be calculated as the sum of the individual item responses at a given visit (total raw scale range 8-40). The total raw scores for the measure will be converted to T-scores using the applicable score conversion table in the user manual and scoring instructions (PROMIS, 2023) ranging from 20.3 to 60.1 with higher scores representing higher reported physical functioning and better outcomes. A T-score of 50 indicates the population mean with a standard deviation of 10.
Time frame: Baseline and Cycle 13 (1 cycle = 28 days), up to 12 months
| Milestone | Treatment Phase - Pediatric Cohort Mirdametinib (PD-0325901) | Treatment Phase - Adult Cohort Mirdametinib (PD-0325901) |
|---|---|---|
| Started | 56 | 58 |
| Completed | 33 | 31 |
| Not completed | 23 | 27 |
| Withdrew: Death | 0 | 1 |
| Withdrew: Withdrawal by subject | 3 | 0 |
| Withdrew: Adverse event | 3 | 12 |
| Withdrew: Lost to follow-up | 1 | 2 |
| Withdrew: Radiographic pd | 9 | 3 |
| Withdrew: Participant decision | 3 | 8 |
| Withdrew: Received procedure not compatible with mri | 0 | 1 |
| Withdrew: Ongoing in the treatment phase | 4 | 0 |
| Milestone | Treatment Phase - Pediatric Cohort Mirdametinib (PD-0325901) | Treatment Phase - Adult Cohort Mirdametinib (PD-0325901) |
|---|---|---|
| Started | 28 | 26 |
| Completed | 0 | 0 |
| Not completed | 28 | 26 |
| Withdrew: Withdrawal by subject | 0 | 1 |
| Withdrew: Adverse event | 1 | 0 |
| Withdrew: Physician decision | 0 | 1 |
| Withdrew: Radiographic pd | 1 | 0 |
| Withdrew: Sponsor request | 1 | 0 |
| Withdrew: Participant decision | 0 | 1 |
| Withdrew: Positive pregnancy test | 0 | 1 |
| Withdrew: Ongoing in the long term follow-up phase phase | 25 | 22 |
Response will be determined by a blinded centralized review of volumetric MRI. The confirmed objective response rate (complete or partial response) by the end of Treatment Phase (i.e., Cycle 24) is defined as the proportion of participants who have a confirmed ≥ 20% reduction in target tumor volume as compared to baseline as assessed by a BICR, and the response needs to be confirmed by BICR in a consecutive tumor assessment within 2 - 6 months. Partial response is defined as a ≥ 20% reduction in target tumor volume from baseline. Complete response is defined as the complete resolution of the target tumor.
| percentage of patients | Treatment Phase - Pediatric Cohort Mirdametinib (PD-0325901) | Treatment Phase - Adult Cohort Mirdametinib (PD-0325901) |
|---|---|---|
| Confirmed Objective Response Rate at the End of the Treatment Phase. | 51.8 (38.0 to 65.3) | 41.4 (28.6 to 55.1) |
All adverse events were coded using MedDRA Version 24.0. Adverse events will be assessed according to toxicities graded by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0.
| percentage of patients | Treatment Phase - Pediatric Cohort Mirdametinib (PD-0325901) | Treatment Phase - Adult Cohort Mirdametinib (PD-0325901) |
|---|---|---|
| Percentage of Patients With Treatment-Emergent Adverse Events. | 100 | 100 |
Duration of response is defined as the time in months between the first instance of response that is subsequently confirmed, until the date of radiographic disease progression or death, whichever occurs first. For participants who enter the LTFU Phase, all MRI assessments in both the Treatment Phase and LTFU Phase will be used to determine duration of response. Participants without radiographic disease progression or death while on study will have their results censored to their most recent adequate (i.e. evaluable) tumor assessment date.
| months | Treatment Phase - Pediatric Cohort Mirdametinib (PD-0325901) | Treatment Phase - Adult Cohort Mirdametinib (PD-0325901) |
|---|---|---|
| Duration of Response (DOR) for Participants Who Meet Criteria for Confirmed Objective Response. | NA (NA to NA) | NA (NA to NA) |
The PedsQL consists of a 23-item core measure of global QOL that can be completed in approximately 5 minutes. There is a total score and four subscales: physical functioning, emotional functioning, social functioning and school/work functioning. Participants ≥ 5 years of age complete an age-appropriate self-report; and parents/guardians of children ages 2-17 complete a parent proxy report of the age-specific QOL. The recall period is 7 days. PedsQL items are answered on a Likert scale with responses ranging from 0 to 4 (where 0 means it is never a problem and 4 means it is almost always a problem). These items are then reverse scored and linearly transformed to a 0-100 scale as follows: 0=100, 1=75, 2=50, 3=25, 4=0. On this scale, higher scores indicate better outcomes. Overall scale scores are calculated as the mean of the scores for the questions in said scale (or of all questions for the total score). The change from baseline is modelled using a mixed-model for repeated measures.
| units on a scale | Treatment Phase - Pediatric Cohort Mirdametinib (PD-0325901) - Self-Report | Treatment Phase - Pediatric Cohort Mirdametinib (PD-0325901) - Parent Proxy | Treatment Phase - Adult Cohort Mirdametinib (PD-0325901) - Self-Report |
|---|---|---|---|
| Total Score | 4.01 (-0.74 to 8.76) | 5.64 (1.75 to 9.53) | 3.94 (0.70 to 7.17) |
| School/Work Functioning | -0.02 (-7.16 to 7.13) | 1.71 (-4.02 to 7.45) | 4.67 (0.52 to 8.82) |
| Social Functioning | 1.85 (-4.31 to 8.01) | 7.64 (2.91 to 12.37) | 2.28 (-1.74 to 6.29) |
| Emotional Functioning | 5.60 (-0.66 to 11.86) | 8.15 (3.71 to 12.58) | 1.51 (-2.78 to 5.80) |
| Physical Functioning | 6.71 (0.56 to 12.87) | 5.75 (0.35 to 11.14) | 5.90 (1.33 to 10.47) |
The NRS-11 is a self-reported 11-point numerical scale that assesses pain severity. Participants ≥ 8 years of age are asked to select a number from 0 (no pain) to 10 (worst pain you can imagine) that best describes their worst pain. The recall period is 24 hours. The change from baseline is modelled using a mixed-model for repeated measures.
| units on a scale | Treatment Phase - Pediatric Cohort Mirdametinib (PD-0325901) - Self-Report | Treatment Phase - Adult Cohort Mirdametinib (PD-0325901) - Self-Report |
|---|---|---|
| Change From Baseline in Pain as Measured by the Numeric Rating Scale-11 (NRS-11) at Cycle 13. | -0.79 (-1.28 to -0.29) | -1.33 (-1.83 to -0.84) |
The PII assesses relevant aspects of one's life, including pain interference with activities, spending time with family/friends, mood, sleep and attention. Participants ≥ 6 years of age complete a self-report, and parents/guardians of children aged 6-17 complete a parent proxy report. The recall period is 24 hours. The PII consists of 6 questions, each asking the responder to select one number from 0 to 6 that best describes how their/their proxy's pain has impacted various items over the past 24 hours with 0 representing "Not at all" and 6 representing "Completely". The mean of the completed items is taken as the PII score for a single assessment. The PII score presented each visit will be taken as the average of the PII scores over the 7 consecutive days up to and including visit day, with no transformation applied. The change from baseline is modelled using a mixed-model for repeated measures.
| units on a scale | Treatment Phase - Pediatric Cohort Mirdametinib (PD-0325901) - Self-Report | Treatment Phase - Pediatric Cohort Mirdametinib (PD-0325901) - Parent Proxy | Treatment Phase - Adult Cohort Mirdametinib (PD-0325901) - Self-Report |
|---|---|---|---|
| Change From Baseline in Pain as Measured by the Pain Interference Index (PII) at Cycle 13. | -0.46 (-0.83 to -0.09) | -0.26 (-0.49 to -0.03) | -0.70 (-1.02 to -0.38) |
Assessment of strength will be conducted only in the area affected by the target tumor. Measurements will be obtained using Medical Research Council (MRC) grading followed by quantitative assessments using the sponsor provided MicroFET2 dynamometer. Dynamometer assessment (in lbs) must be conducted in accordance with the study reference manual. For each participant, the sum of the dynamometer scores for the muscle groups tested will be taken as an overall score for each visit with higher scores indicating better localized strength. To assess the change from baseline at a visit, a participant will need assessments in which all the following categories, as assessed at baseline, match at that visit: side affected, position during assessment (sitting/supine/lateral decubitus), muscle group assessed. The change from baseline in localized strength measured by the sum of the dynamometer scores for the muscle groups tested will be assessed at Cycle 13.
| lbs | Treatment Phase - Pediatric Cohort Mirdametinib (PD-0325901) | Treatment Phase - Adult Cohort Mirdametinib (PD-0325901) |
|---|---|---|
| Change From Baseline in Localized Strength (Dynamometer) at Cycle 13. | 18.8 ± 31.93 | 68.5 ± 130.33 |
If motor dysfunction or weakness is evident, range of motion of the affected areas and/or joints will be measured by a goniometer.
| degrees | Treatment Phase - Pediatric Cohort Mirdametinib (PD-0325901) | Treatment Phase - Adult Cohort Mirdametinib (PD-0325901) |
|---|---|---|
| Change From Baseline in Range of Motion of PN-Associated Functional Impairment at Cycle 13. | -6.1 ± 82.06 | 17.7 ± 51.28 |
If airway or lower extremity motor dysfunction is evident, endurance will be measured by completion of a 6-minute walking test.
| meters | Treatment Phase - Pediatric Cohort Mirdametinib (PD-0325901) | Treatment Phase - Adult Cohort Mirdametinib (PD-0325901) |
|---|---|---|
| Change From Baseline in Endurance at Cycle 13. | -6.8 ± 60.76 | 2.2 ± 70.41 |
Response will be determined by a blinded centralized review of volumetric MRI. Time to response is defined as the time in months from the start of treatment to the date of first response that was subsequently confirmed.
| months | Treatment Phase - Pediatric Cohort Mirdametinib (PD-0325901) | Treatment Phase - Adult Cohort Mirdametinib (PD-0325901) |
|---|---|---|
| Time to Response Defined as the Time Between First Dose and the First Date of Objective Response That is Subsequently Confirmed. | 8.63 ± 4.801 | 9.71 ± 5.804 |
Evidence of progression or tumor growth will be determined by a blinded centralized review of volumetric MRI. Time to progression is defined as the time in months between the first treatment date until the date of radiographic disease progression. For participants who enter the LTFU Phase, all MRI assessments in both the Treatment Phase and LTFU Phase will be used to determine time to progression. Participants without radiographic disease progression will have their results censored to their most recent adequate (i.e. evaluable) tumor assessment date.
| months | Treatment Phase - Pediatric Cohort Mirdametinib (PD-0325901) | Treatment Phase - Adult Cohort Mirdametinib (PD-0325901) |
|---|---|---|
| Time to Progression, From the First Dose to the First Date of a ≥ 20% Increase in Tumor Volume From Baseline. | NA (NA to NA) | NA (NA to NA) |
Evidence of progression or tumor growth will be determined by a blinded centralized review of volumetric MRI. Progression free survival is defined as the time in months between the first treatment date, until the date of radiographic disease progression or death, whichever occurs first. For participants who enter the LTFU Phase, all MRI assessments in both the Treatment Phase and LTFU Phase will be used to determine progression free survival. Participants without radiographic disease progression or death while on study will have their results censored to their most recent adequate (i.e. evaluable) tumor assessment date.
| months | Treatment Phase - Pediatric Cohort Mirdametinib (PD-0325901) | Treatment Phase - Adult Cohort Mirdametinib (PD-0325901) |
|---|---|---|
| Progression Free Survival, Defined as the Time in Months From the First Dose to the Date of the First ≥ 20% Increase in Tumor Volume From Baseline or Death. | NA (NA to NA) | NA (NA to NA) |
For participants with a PN that is visible and amenable to photography, changes in visible tumor aspects will be evaluated by a centralized reviewer.
Results for this outcome have not been posted.
Measured in tumor biopsies in participants ≥ 18 years of age.
Results for this outcome have not been posted.
The Pediatric Oral Medicine Acceptability Questionnaire (P-OMAQ) uses a 5-point numerical rate scale to measure acceptability of use of the tablet formulation with questions related to taste, smell and administration of study medication. Participants ≥ 8 years of age complete a 12-item self-report; adult parents/caregivers responsible for oversight of study drug administration for participants ages 6 months to 17 years complete a 19-item caregiver report. Each questionnaire is provided with a "past 7 days" recall with all items using a 5-point Numerical Rate Scale (1 to 5) with higher item-scores reflecting greater oral treatment acceptability. The overall P-OMAQ-P (pediatric self-report) and P-OMAQ-C (adult caregiver) scores for a participant in the study will be taken as the mean of all answered questions on the respective questionnaire.
| units on a scale | Treatment Phase - Pediatric Cohort Mirdametinib (PD-0325901) | Adult Caregiver Mirdametinib (PD-0325901) |
|---|---|---|
| P-OMAQ-P | 4.3 ± 0.87 | NA ± NA |
| P-OMAQ-C | NA ± NA | 4.56 ± 0.586 |
If motor dysfunction or weakness is evident, strength of the affected muscle groups will be measured by dynamometer and assessed by a muscle grading scale. Medical Research Council (MRC) Scale grading (0-5) must be conducted in accordance with the study reference manual. MRC Grading is assessed on a scale of 0 to 5, with 0 representing no movement being observed, and 5 representing the muscle contracting normally against full resistance. To assess the change from baseline at a visit, a participant will need assessments in which all the following categories, as assessed at baseline, match at that visit: side affected, position during assessment (sitting/supine/lateral decubitus), muscle group assessed. The MRC Grade visit score is calculated for each participant separately, and these scores are then averaged.
| units on a scale | Treatment Phase - Pediatric Cohort Mirdametinib (PD-0325901) | Treatment Phase - Adult Cohort Mirdametinib (PD-0325901) |
|---|---|---|
| Change From Baseline in Localized Strength (Medical Research Council (MRC) Scale Grading) at Cycle 13. | 0.3 ± 0.35 | 0.3 ± 0.46 |
PROMIS measures capability of physical functioning, with questions related to daily activities. Participants 8-17 years complete a self-report of physical function in the upper extremity or lower extremity (mobility), depending on the location of the PN. The recall period is 7 days. All PROMIS items are answered on a Likert scale with responses ranging from 1 to 5, with higher scores representing higher reported mobility. The total raw score will be calculated as the sum of the individual item responses at a given visit (total raw scale range 8-40). The total raw scores for the measure will be converted to T-scores using the applicable score conversion table in the user manual and scoring instructions (PROMIS, 2023) ranging from 14 to 59 for self-report, and 14 to 56 for parent proxy with higher scores representing higher reported mobility and better outcomes. A T-score of 50 indicates the population mean with a standard deviation of 10.
| T-score | Treatment Phase - Pediatric Cohort Mirdametinib (PD-0325901) - Self-Report | Treatment Phase - Pediatric Cohort Mirdametinib (PD-0325901) - Parent Proxy |
|---|---|---|
| Change From Baseline in Physical Function Status as Measured by the Patient-Reported Outcomes Measurement Information System (PROMIS) at Cycle 13: Pediatric v2.0 Mobility 8a. | 7.0 ± 5.66 | 2.8 ± 5.67 |
PROMIS measures capability of physical functioning, with questions related to daily activities. Participants 8-17 years complete a self-report of physical function in the upper extremity or lower extremity (mobility), depending on the location of the PN. The recall period is 7 days. All PROMIS items are answered on a Likert scale with responses ranging from 1 to 5, with higher scores representing higher physical functioning in the upper extremities. The total raw score will be calculated as the sum of the individual item responses at a given visit (total raw scale range 8-40). The total raw scores for the measure will be converted to T-scores using the applicable score conversion table in the user manual and scoring instructions (PROMIS, 2023) ranging from 10 to 57 for self-report, and 13 to 55 for parent proxy with higher scores representing higher reported physical functioning and better outcomes. A T-score of 50 indicates the population mean with a standard deviation of 10.
| T-score | Treatment Phase - Pediatric Cohort Mirdametinib (PD-0325901) - Self-Report | Treatment Phase - Pediatric Cohort Mirdametinib (PD-0325901) - Parent Proxy |
|---|---|---|
| Change From Baseline in Physical Function Status as Measured by the Patient-Reported Outcomes Measurement Information System (PROMIS) at Cycle 13: Pediatric v2.0 Upper Extremities 8a. | 11.5 ± 3.54 | 9.5 ± 3.54 |
PROMIS measures capability of physical functioning, with questions related to daily activities. Participants ≥ 18 years with a target PN impacting physical functioning complete a self-report of physical function. The recall period is 7 days. All PROMIS items are answered on a Likert scale with responses ranging from 1 to 5, with higher scores representing higher reported physical capability. The total raw score will be calculated as the sum of the individual item responses at a given visit (total raw scale range 8-40). The total raw scores for the measure will be converted to T-scores using the applicable score conversion table in the user manual and scoring instructions (PROMIS, 2023) ranging from 20.3 to 60.1 with higher scores representing higher reported physical functioning and better outcomes. A T-score of 50 indicates the population mean with a standard deviation of 10.
| T-score | Treatment Phase - Adult Cohort Mirdametinib (PD-0325901) - Self-Report |
|---|---|
| Change From Baseline in Physical Function Status as Measured by the Patient-Reported Outcomes Measurement Information System (PROMIS) at Cycle 13: Adult v2.0 Physical Function 8b. | 2.42 ± 9.447 |
Collected over All SAEs and AEs were collected from the time of signing ICF until 30 days after the last dose of study treatment, an average of 1 year and 10 months and up to 3 years and 10 months.. Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Treatment Phase - Pediatric Cohort Mirdametinib (PD-0325901) | 0/56 (0%) | 8/56 (14.3%) | 56/56 (100%) |
| Treatment Phase - Adult Cohort Mirdametinib (PD-0325901) | 1/58 (1.7%) | 10/58 (17.2%) | 57/58 (98.3%) |
| Event | Treatment Phase - Pediatric Cohort Mirdametinib (PD-0325901) | Treatment Phase - Adult Cohort Mirdametinib (PD-0325901) |
|---|---|---|
| COVID-19Infections and infestations | 0/56 | 2/58 |
| NephrolithiasisRenal and urinary disorders | 0/56 | 2/58 |
| Gastrointestinal viral infectionInfections and infestations | 1/56 | 0/58 |
| Rotavirus infectionInfections and infestations | 1/56 | 0/58 |
| FallInjury, poisoning and procedural complications | 1/56 | 0/58 |
| Femoral neck fractureInjury, poisoning and procedural complications | 1/56 | 0/58 |
| Near drowningInjury, poisoning and procedural complications | 1/56 | 0/58 |
| DiplopiaEye disorders | 1/56 | 0/58 |
| SeizureNervous system disorders | 1/56 | 0/58 |
| Non-cardiac chest painGeneral disorders | 1/56 | 0/58 |
| Event | Treatment Phase - Pediatric Cohort Mirdametinib (PD-0325901) | Treatment Phase - Adult Cohort Mirdametinib (PD-0325901) |
|---|---|---|
| Dermatitis acneiformSkin and subcutaneous tissue disorders | 24/56 | 45/58 |
| DiarrhoeaGastrointestinal disorders | 31/56 | 34/58 |
| NauseaGastrointestinal disorders | 15/56 | 30/58 |
| VomitingGastrointestinal disorders | 22/56 | 22/58 |
| HeadacheNervous system disorders | 19/56 | 6/58 |
| ParonychiaInfections and infestations | 18/56 | 1/58 |
| FatigueGeneral disorders | 7/56 | 17/58 |
| Abdominal painGastrointestinal disorders | 15/56 | 10/58 |
| Ejection fraction decreasedInvestigations | 15/56 | 9/58 |
| COVID-19Infections and infestations | 14/56 | 13/58 |
Full Analysis Set (Received At Least One Dose of Mirdametinib)
| Age, Continuous(years) | Treatment Phase - Pediatric Cohort Mirdametinib (PD-0325901) | Treatment Phase - Adult Cohort Mirdametinib (PD-0325901) | Total |
|---|---|---|---|
| Mean | 10.1 ± 4.50 | 35.0 ± 13.17 | 22.8 ± 15.94 |
| Sex: Female, Male(Participants) | Treatment Phase - Pediatric Cohort Mirdametinib (PD-0325901) | Treatment Phase - Adult Cohort Mirdametinib (PD-0325901) | Total |
|---|---|---|---|
| Female | 30 | 37 | 67 |
| Male | 26 | 21 | 47 |
| Ethnicity (NIH/OMB)(Participants) | Treatment Phase - Pediatric Cohort Mirdametinib (PD-0325901) | Treatment Phase - Adult Cohort Mirdametinib (PD-0325901) | Total |
|---|---|---|---|
| Hispanic or Latino | 8 | 1 | 9 |
| Not Hispanic or Latino | 44 | 52 | 96 |
| Unknown or Not Reported | 4 | 5 | 9 |
| Race (NIH/OMB)(Participants) | Treatment Phase - Pediatric Cohort Mirdametinib (PD-0325901) | Treatment Phase - Adult Cohort Mirdametinib (PD-0325901) | Total |
|---|---|---|---|
| American Indian or Alaska Native | 1 | 0 | 1 |
| Asian | 2 | 2 | 4 |
| Native Hawaiian or Other Pacific Islander | 0 | 0 | 0 |
| Black or African American | 11 | 5 | 16 |
| White | 37 | 49 | 86 |
| More than one race | 0 | 0 | 0 |
| Unknown or Not Reported | 5 | 2 | 7 |
| Region of Enrollment(participants) | Treatment Phase - Pediatric Cohort Mirdametinib (PD-0325901) | Treatment Phase - Adult Cohort Mirdametinib (PD-0325901) | Total |
|---|---|---|---|
| United States | 56 | 58 | 114 |
| Karnofsky/Lansky Score(units on a scale) | Treatment Phase - Pediatric Cohort Mirdametinib (PD-0325901) | Treatment Phase - Adult Cohort Mirdametinib (PD-0325901) | Total |
|---|---|---|---|
| Mean | 94.5 ± 9.33 | 87.1 ± 7.73 | 90.7 ± 9.29 |
| Childbearing Potential at Screening(Participants) | Treatment Phase - Pediatric Cohort Mirdametinib (PD-0325901) | Treatment Phase - Adult Cohort Mirdametinib (PD-0325901) | Total |
|---|---|---|---|
| Yes | 15 | 29 | 44 |
| No | 15 | 8 | 23 |
PDFs hosted by the registry, ClinicalTrials.gov.
Plan to share: Yes — IPD supporting publicly available results will be evaluated for sharing.
Supporting information: Study protocol, Statistical analysis plan, Clinical study report, Analytic code
Time frame: IPD from completed trials will be publicly available within 6 months after all of the following events: Approval of a product/new indication by major authorities (FDA, EMA, PMDA if requested) with no pending submissions Public results via primary manuscript or trial registry disclosure Legal authority to share data Privacy protections are in place If approval is not sought or development is globally discontinued, data will be publicly available within 18 months after global trial completion. Further information on how to request data can be found on our website bit.ly/IPD21
Access criteria: Qualified researchers may propose access to IPD from sponsored trials via https://vivli.org/members/ourmembers/
Data sharing details ↗ · vivli.org
Ran from Sep 2019 to primary completion in Sep 2023, 47 months.
Results were first posted in Aug 2025, 1 year 10 months after primary completion. A results delay was requested in Aug 2024.
How these figures are worked out, and which studies are left out of them.
From the registry record's own update history. This site started tracking changes on Sep 25, 2026; for anything earlier, see the record history on ClinicalTrials.gov ↗
This study is active, not recruiting, as verified in Sep 2026. You cannot join it, but the record below documents what was studied.
Get an email when the registry record changes — status, dates, results — or when someone posts here.
Sign in to followQuestions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.
Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.
Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.
Studies of the drug tested here: Mirdametinib
SpringWorks Therapeutics, Inc., a healthcare company of Merck KGaA, Darmstadt, Germany →