Trial Outcomes & Findings for MEK Inhibitor Mirdametinib (PD-0325901) in Patients With Neurofibromatosis Type 1 Associated Plexiform Neurofibromas (NCT NCT03962543)

Last Updated: 2025-08-07

Results Overview

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.

Recruitment status

ACTIVE_NOT_RECRUITING

Study phase

PHASE2

Target enrollment

114 participants

Primary outcome timeframe

Up to 24 months

Results posted on

2025-08-07

Participant Flow

Participant milestones

Participant milestones
Measure	Treatment Phase - Pediatric Cohort Mirdametinib (PD-0325901) Patients aged 2 to 17 years old at the time of informed consent. Mirdametinib (PD-0325901) capsule or dispersible tablet 2 mg/m\^2 (maximum dose of 4 mg) by mouth twice daily	Treatment Phase - Adult Cohort Mirdametinib (PD-0325901) Patients aged 18 and above at the time of informed consent. Mirdametinib (PD-0325901) capsule or dispersible tablet 2 mg/m\^2 (maximum dose of 4 mg) by mouth twice daily
Treatment Phase STARTED	56	58
Treatment Phase COMPLETED	33	31
Treatment Phase NOT COMPLETED	23	27
Long Term Follow-Up Phase STARTED	28	26
Long Term Follow-Up Phase COMPLETED	0	0
Long Term Follow-Up Phase NOT COMPLETED	28	26

Reasons for withdrawal

Reasons for withdrawal
Measure	Treatment Phase - Pediatric Cohort Mirdametinib (PD-0325901) Patients aged 2 to 17 years old at the time of informed consent. Mirdametinib (PD-0325901) capsule or dispersible tablet 2 mg/m\^2 (maximum dose of 4 mg) by mouth twice daily	Treatment Phase - Adult Cohort Mirdametinib (PD-0325901) Patients aged 18 and above at the time of informed consent. Mirdametinib (PD-0325901) capsule or dispersible tablet 2 mg/m\^2 (maximum dose of 4 mg) by mouth twice daily
Treatment Phase Death	0	1
Treatment Phase Withdrawal by Subject	3	0
Treatment Phase Adverse Event	3	12
Treatment Phase Lost to Follow-up	1	2
Treatment Phase Radiographic PD	9	3
Treatment Phase Participant Decision	3	8
Treatment Phase Received procedure not compatible with MRI	0	1
Treatment Phase Ongoing in the Treatment Phase	4	0
Long Term Follow-Up Phase Withdrawal by Subject	0	1
Long Term Follow-Up Phase Adverse Event	1	0
Long Term Follow-Up Phase Physician Decision	0	1
Long Term Follow-Up Phase Radiographic PD	1	0
Long Term Follow-Up Phase Sponsor Request	1	0
Long Term Follow-Up Phase Participant Decision	0	1
Long Term Follow-Up Phase Positive pregnancy test	0	1
Long Term Follow-Up Phase Ongoing in the Long Term Follow-Up Phase Phase	25	22

Baseline Characteristics

Based on the number of female patients in the Full Analysis Set

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Treatment Phase - Pediatric Cohort Mirdametinib (PD-0325901) n=56 Participants Patients aged 2 to 17 years old at the time of informed consent. Mirdametinib (PD-0325901) capsule or dispersible tablet 2 mg/m\^2 (maximum dose of 4 mg) by mouth twice daily	Treatment Phase - Adult Cohort Mirdametinib (PD-0325901) n=58 Participants Patients aged 18 and above at the time of informed consent. Mirdametinib (PD-0325901) capsule or dispersible tablet 2 mg/m\^2 (maximum dose of 4 mg) by mouth twice daily	Total n=114 Participants Total of all reporting groups
Age, Continuous	10.1 years STANDARD_DEVIATION 4.50 • n=56 Participants	35.0 years STANDARD_DEVIATION 13.17 • n=58 Participants	22.8 years STANDARD_DEVIATION 15.94 • n=114 Participants
Sex: Female, Male Female	30 Participants n=56 Participants	37 Participants n=58 Participants	67 Participants n=114 Participants
Sex: Female, Male Male	26 Participants n=56 Participants	21 Participants n=58 Participants	47 Participants n=114 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	8 Participants n=56 Participants	1 Participants n=58 Participants	9 Participants n=114 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	44 Participants n=56 Participants	52 Participants n=58 Participants	96 Participants n=114 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	4 Participants n=56 Participants	5 Participants n=58 Participants	9 Participants n=114 Participants
Race (NIH/OMB) American Indian or Alaska Native	1 Participants n=56 Participants	0 Participants n=58 Participants	1 Participants n=114 Participants
Race (NIH/OMB) Asian	2 Participants n=56 Participants	2 Participants n=58 Participants	4 Participants n=114 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=56 Participants	0 Participants n=58 Participants	0 Participants n=114 Participants
Race (NIH/OMB) Black or African American	11 Participants n=56 Participants	5 Participants n=58 Participants	16 Participants n=114 Participants
Race (NIH/OMB) White	37 Participants n=56 Participants	49 Participants n=58 Participants	86 Participants n=114 Participants
Race (NIH/OMB) More than one race	0 Participants n=56 Participants	0 Participants n=58 Participants	0 Participants n=114 Participants
Race (NIH/OMB) Unknown or Not Reported	5 Participants n=56 Participants	2 Participants n=58 Participants	7 Participants n=114 Participants
Region of Enrollment United States	56 participants n=56 Participants	58 participants n=58 Participants	114 participants n=114 Participants
Karnofsky/Lansky Score	94.5 units on a scale STANDARD_DEVIATION 9.33 • n=56 Participants	87.1 units on a scale STANDARD_DEVIATION 7.73 • n=58 Participants	90.7 units on a scale STANDARD_DEVIATION 9.29 • n=114 Participants
Childbearing Potential at Screening Yes	15 Participants n=30 Participants • Based on the number of female patients in the Full Analysis Set	29 Participants n=37 Participants • Based on the number of female patients in the Full Analysis Set	44 Participants n=67 Participants • Based on the number of female patients in the Full Analysis Set
Childbearing Potential at Screening No	15 Participants n=30 Participants • Based on the number of female patients in the Full Analysis Set	8 Participants n=37 Participants • Based on the number of female patients in the Full Analysis Set	23 Participants n=67 Participants • Based on the number of female patients in the Full Analysis Set

PRIMARY outcome

Timeframe: Up to 24 months

Population: The Full Analysis Set is defined as patients who received at least one dose of Mirdametinib.

Outcome measures

Outcome measures
Measure	Treatment Phase - Pediatric Cohort Mirdametinib (PD-0325901) n=56 Participants Patients aged 2 to 17 years old at the time of informed consent. Mirdametinib (PD-0325901) capsule or dispersible tablet 2 mg/m\^2 (maximum dose of 4 mg) by mouth twice daily	Treatment Phase - Adult Cohort Mirdametinib (PD-0325901) n=58 Participants Patients aged 18 and above at the time of informed consent. Mirdametinib (PD-0325901) capsule or dispersible tablet 2 mg/m\^2 (maximum dose of 4 mg) by mouth twice daily	Treatment Phase - Adult Cohort Mirdametinib (PD-0325901) - Self-Report Patients self-reported results aged 18 years and above at the time of informed consent. Mirdametinib (PD-0325901) capsule or dispersible tablet 2 mg/m\^2 (maximum dose of 4 mg) by mouth twice daily
Confirmed Objective Response Rate at the End of the Treatment Phase.	51.8 percentage of patients Interval 38.0 to 65.3	41.4 percentage of patients Interval 28.6 to 55.1	—

SECONDARY outcome

Timeframe: 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.

Population: The Full Analysis Set includes patients who received at least one dose of Mirdametinib.

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.

Outcome measures

Outcome measures
Measure	Treatment Phase - Pediatric Cohort Mirdametinib (PD-0325901) n=56 Participants Patients aged 2 to 17 years old at the time of informed consent. Mirdametinib (PD-0325901) capsule or dispersible tablet 2 mg/m\^2 (maximum dose of 4 mg) by mouth twice daily	Treatment Phase - Adult Cohort Mirdametinib (PD-0325901) n=58 Participants Patients aged 18 and above at the time of informed consent. Mirdametinib (PD-0325901) capsule or dispersible tablet 2 mg/m\^2 (maximum dose of 4 mg) by mouth twice daily	Treatment Phase - Adult Cohort Mirdametinib (PD-0325901) - Self-Report Patients self-reported results aged 18 years and above at the time of informed consent. Mirdametinib (PD-0325901) capsule or dispersible tablet 2 mg/m\^2 (maximum dose of 4 mg) by mouth twice daily
Percentage of Patients With Treatment-Emergent Adverse Events.	100 percentage of patients	100 percentage of patients	—

SECONDARY outcome

Timeframe: 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

Population: The Full Analysis Set patients with 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.

Outcome measures

Outcome measures
Measure	Treatment Phase - Pediatric Cohort Mirdametinib (PD-0325901) n=29 Participants Patients aged 2 to 17 years old at the time of informed consent. Mirdametinib (PD-0325901) capsule or dispersible tablet 2 mg/m\^2 (maximum dose of 4 mg) by mouth twice daily	Treatment Phase - Adult Cohort Mirdametinib (PD-0325901) n=24 Participants Patients aged 18 and above at the time of informed consent. Mirdametinib (PD-0325901) capsule or dispersible tablet 2 mg/m\^2 (maximum dose of 4 mg) by mouth twice daily	Treatment Phase - Adult Cohort Mirdametinib (PD-0325901) - Self-Report Patients self-reported results aged 18 years and above at the time of informed consent. Mirdametinib (PD-0325901) capsule or dispersible tablet 2 mg/m\^2 (maximum dose of 4 mg) by mouth twice daily
Duration of Response (DOR) for Participants Who Meet Criteria for Confirmed Objective Response.	NA months Not reached. Only less than 50% of the patients had events in the Pediatric cohort.	NA months Not reached. Only less than 50% of the patients had events in the Adult cohort.	—

SECONDARY outcome

Timeframe: Baseline and Cycle 13 (1 cycle = 28 days), up to 12 months

Population: The Full Analysis Set patients who are eligible for the Peds-QL assessments at baseline.

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.

Outcome measures

Outcome measures
Measure	Treatment Phase - Pediatric Cohort Mirdametinib (PD-0325901) n=50 Participants Patients aged 2 to 17 years old at the time of informed consent. Mirdametinib (PD-0325901) capsule or dispersible tablet 2 mg/m\^2 (maximum dose of 4 mg) by mouth twice daily	Treatment Phase - Adult Cohort Mirdametinib (PD-0325901) n=56 Participants Patients aged 18 and above at the time of informed consent. Mirdametinib (PD-0325901) capsule or dispersible tablet 2 mg/m\^2 (maximum dose of 4 mg) by mouth twice daily	Treatment Phase - Adult Cohort Mirdametinib (PD-0325901) - Self-Report n=58 Participants Patients self-reported results aged 18 years and above at the time of informed consent. Mirdametinib (PD-0325901) capsule or dispersible tablet 2 mg/m\^2 (maximum dose of 4 mg) by mouth twice daily
Change From Baseline on Quality of Life (QOL) as Measured by the Pediatric Quality of Life Inventory (PedsQL) at Cycle 13, Acute Version. Total Score	4.01 units on a scale Interval -0.74 to 8.76	5.64 units on a scale Interval 1.75 to 9.53	3.94 units on a scale Interval 0.7 to 7.17
Change From Baseline on Quality of Life (QOL) as Measured by the Pediatric Quality of Life Inventory (PedsQL) at Cycle 13, Acute Version. School/Work Functioning	-0.02 units on a scale Interval -7.16 to 7.13	1.71 units on a scale Interval -4.02 to 7.45	4.67 units on a scale Interval 0.52 to 8.82
Change From Baseline on Quality of Life (QOL) as Measured by the Pediatric Quality of Life Inventory (PedsQL) at Cycle 13, Acute Version. Social Functioning	1.85 units on a scale Interval -4.31 to 8.01	7.64 units on a scale Interval 2.91 to 12.37	2.28 units on a scale Interval -1.74 to 6.29
Change From Baseline on Quality of Life (QOL) as Measured by the Pediatric Quality of Life Inventory (PedsQL) at Cycle 13, Acute Version. Emotional Functioning	5.60 units on a scale Interval -0.66 to 11.86	8.15 units on a scale Interval 3.71 to 12.58	1.51 units on a scale Interval -2.78 to 5.8
Change From Baseline on Quality of Life (QOL) as Measured by the Pediatric Quality of Life Inventory (PedsQL) at Cycle 13, Acute Version. Physical Functioning	6.71 units on a scale Interval 0.56 to 12.87	5.75 units on a scale Interval 0.35 to 11.14	5.90 units on a scale Interval 1.33 to 10.47

SECONDARY outcome

Timeframe: Baseline and Cycle 13 (1 cycle = 28 days), up to 12 months

Population: The Full Analysis Set patients eligible for the instrument at baseline.

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.

Outcome measures

Outcome measures
Measure	Treatment Phase - Pediatric Cohort Mirdametinib (PD-0325901) n=37 Participants Patients aged 2 to 17 years old at the time of informed consent. Mirdametinib (PD-0325901) capsule or dispersible tablet 2 mg/m\^2 (maximum dose of 4 mg) by mouth twice daily	Treatment Phase - Adult Cohort Mirdametinib (PD-0325901) n=58 Participants Patients aged 18 and above at the time of informed consent. Mirdametinib (PD-0325901) capsule or dispersible tablet 2 mg/m\^2 (maximum dose of 4 mg) by mouth twice daily	Treatment Phase - Adult Cohort Mirdametinib (PD-0325901) - Self-Report Patients self-reported results aged 18 years and above at the time of informed consent. Mirdametinib (PD-0325901) capsule or dispersible tablet 2 mg/m\^2 (maximum dose of 4 mg) by mouth twice daily
Change From Baseline in Pain as Measured by the Numeric Rating Scale-11 (NRS-11) at Cycle 13.	-0.79 units on a scale Interval -1.28 to -0.29	-1.33 units on a scale Interval -1.83 to -0.84	—

SECONDARY outcome

Timeframe: Baseline and Cycle 13 (1 cycle = 28 days), up to 12 months

Population: The Full Analysis Set patients eligible for the instrument at baseline.

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.

Outcome measures

Outcome measures
Measure	Treatment Phase - Pediatric Cohort Mirdametinib (PD-0325901) n=47 Participants Patients aged 2 to 17 years old at the time of informed consent. Mirdametinib (PD-0325901) capsule or dispersible tablet 2 mg/m\^2 (maximum dose of 4 mg) by mouth twice daily	Treatment Phase - Adult Cohort Mirdametinib (PD-0325901) n=47 Participants Patients aged 18 and above at the time of informed consent. Mirdametinib (PD-0325901) capsule or dispersible tablet 2 mg/m\^2 (maximum dose of 4 mg) by mouth twice daily	Treatment Phase - Adult Cohort Mirdametinib (PD-0325901) - Self-Report n=58 Participants Patients self-reported results aged 18 years and above at the time of informed consent. Mirdametinib (PD-0325901) capsule or dispersible tablet 2 mg/m\^2 (maximum dose of 4 mg) by mouth twice daily
Change From Baseline in Pain as Measured by the Pain Interference Index (PII) at Cycle 13.	-0.46 units on a scale Interval -0.83 to -0.09	-0.26 units on a scale Interval -0.49 to -0.03	-0.70 units on a scale Interval -1.02 to -0.38

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline and Cycle 13 (1 cycle = 28 days), up to 12 months

Population: The Full Analysis Set patients eligible for this instrument at baseline.

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.

Outcome measures

Outcome measures
Measure	Treatment Phase - Pediatric Cohort Mirdametinib (PD-0325901) n=15 Participants Patients aged 2 to 17 years old at the time of informed consent. Mirdametinib (PD-0325901) capsule or dispersible tablet 2 mg/m\^2 (maximum dose of 4 mg) by mouth twice daily	Treatment Phase - Adult Cohort Mirdametinib (PD-0325901) n=23 Participants Patients aged 18 and above at the time of informed consent. Mirdametinib (PD-0325901) capsule or dispersible tablet 2 mg/m\^2 (maximum dose of 4 mg) by mouth twice daily	Treatment Phase - Adult Cohort Mirdametinib (PD-0325901) - Self-Report Patients self-reported results aged 18 years and above at the time of informed consent. Mirdametinib (PD-0325901) capsule or dispersible tablet 2 mg/m\^2 (maximum dose of 4 mg) by mouth twice daily
Change From Baseline in Localized Strength (Dynamometer) at Cycle 13.	18.8 lbs Standard Deviation 31.93	68.5 lbs Standard Deviation 130.33	—

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline and Cycle 13 (1 cycle = 28 days), up to 12 months

Population: The Full Analysis Set patients who are eligible for this instrument at baseline.

If motor dysfunction or weakness is evident, range of motion of the affected areas and/or joints will be measured by a goniometer.

Outcome measures

Outcome measures
Measure	Treatment Phase - Pediatric Cohort Mirdametinib (PD-0325901) n=15 Participants Patients aged 2 to 17 years old at the time of informed consent. Mirdametinib (PD-0325901) capsule or dispersible tablet 2 mg/m\^2 (maximum dose of 4 mg) by mouth twice daily	Treatment Phase - Adult Cohort Mirdametinib (PD-0325901) n=23 Participants Patients aged 18 and above at the time of informed consent. Mirdametinib (PD-0325901) capsule or dispersible tablet 2 mg/m\^2 (maximum dose of 4 mg) by mouth twice daily	Treatment Phase - Adult Cohort Mirdametinib (PD-0325901) - Self-Report Patients self-reported results aged 18 years and above at the time of informed consent. Mirdametinib (PD-0325901) capsule or dispersible tablet 2 mg/m\^2 (maximum dose of 4 mg) by mouth twice daily
Change From Baseline in Range of Motion of PN-Associated Functional Impairment at Cycle 13.	-6.1 degrees Standard Deviation 82.06	17.7 degrees Standard Deviation 51.28	—

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline and Cycle 13 (1 cycle = 28 days), up to 12 months

Population: The Full Analysis Set patients eligible for this instrument at baseline

If airway or lower extremity motor dysfunction is evident, endurance will be measured by completion of a 6-minute walking test.

Outcome measures

Outcome measures
Measure	Treatment Phase - Pediatric Cohort Mirdametinib (PD-0325901) n=11 Participants Patients aged 2 to 17 years old at the time of informed consent. Mirdametinib (PD-0325901) capsule or dispersible tablet 2 mg/m\^2 (maximum dose of 4 mg) by mouth twice daily	Treatment Phase - Adult Cohort Mirdametinib (PD-0325901) n=16 Participants Patients aged 18 and above at the time of informed consent. Mirdametinib (PD-0325901) capsule or dispersible tablet 2 mg/m\^2 (maximum dose of 4 mg) by mouth twice daily	Treatment Phase - Adult Cohort Mirdametinib (PD-0325901) - Self-Report Patients self-reported results aged 18 years and above at the time of informed consent. Mirdametinib (PD-0325901) capsule or dispersible tablet 2 mg/m\^2 (maximum dose of 4 mg) by mouth twice daily
Change From Baseline in Endurance at Cycle 13.	-6.8 meters Standard Deviation 60.76	2.2 meters Standard Deviation 70.41	—

OTHER_PRE_SPECIFIED outcome

Timeframe: Up to 24 months

Population: The Full Analysis Set patients who achieved confirmed objective response.

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.

Outcome measures

Outcome measures
Measure	Treatment Phase - Pediatric Cohort Mirdametinib (PD-0325901) n=29 Participants Patients aged 2 to 17 years old at the time of informed consent. Mirdametinib (PD-0325901) capsule or dispersible tablet 2 mg/m\^2 (maximum dose of 4 mg) by mouth twice daily	Treatment Phase - Adult Cohort Mirdametinib (PD-0325901) n=24 Participants Patients aged 18 and above at the time of informed consent. Mirdametinib (PD-0325901) capsule or dispersible tablet 2 mg/m\^2 (maximum dose of 4 mg) by mouth twice daily	Treatment Phase - Adult Cohort Mirdametinib (PD-0325901) - Self-Report Patients self-reported results aged 18 years and above at the time of informed consent. Mirdametinib (PD-0325901) capsule or dispersible tablet 2 mg/m\^2 (maximum dose of 4 mg) by mouth twice daily
Time to Response Defined as the Time Between First Dose and the First Date of Objective Response That is Subsequently Confirmed.	8.63 months Standard Deviation 4.801	9.71 months Standard Deviation 5.804	—

OTHER_PRE_SPECIFIED outcome

Timeframe: 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

Population: The Full Analysis Set defined as all patients who received at least one dose of Mirdametinib.

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.

Outcome measures

Outcome measures
Measure	Treatment Phase - Pediatric Cohort Mirdametinib (PD-0325901) n=56 Participants Patients aged 2 to 17 years old at the time of informed consent. Mirdametinib (PD-0325901) capsule or dispersible tablet 2 mg/m\^2 (maximum dose of 4 mg) by mouth twice daily	Treatment Phase - Adult Cohort Mirdametinib (PD-0325901) n=58 Participants Patients aged 18 and above at the time of informed consent. Mirdametinib (PD-0325901) capsule or dispersible tablet 2 mg/m\^2 (maximum dose of 4 mg) by mouth twice daily	Treatment Phase - Adult Cohort Mirdametinib (PD-0325901) - Self-Report Patients self-reported results aged 18 years and above at the time of informed consent. Mirdametinib (PD-0325901) capsule or dispersible tablet 2 mg/m\^2 (maximum dose of 4 mg) by mouth twice daily
Time to Progression, From the First Dose to the First Date of a ≥ 20% Increase in Tumor Volume From Baseline.	NA months NA Explanation: Not reached. Only less than 50% of the patients had events in the Pediatric cohort.	NA months NA Explanation: Not reached. Only less than 50% of the patients had events in the Adult cohort.	—

OTHER_PRE_SPECIFIED outcome

Timeframe: 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

Population: The Full Analysis Set defined as all patients who received at least one dose of Mirdametinib.

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.

Outcome measures

Outcome measures
Measure	Treatment Phase - Pediatric Cohort Mirdametinib (PD-0325901) n=56 Participants Patients aged 2 to 17 years old at the time of informed consent. Mirdametinib (PD-0325901) capsule or dispersible tablet 2 mg/m\^2 (maximum dose of 4 mg) by mouth twice daily	Treatment Phase - Adult Cohort Mirdametinib (PD-0325901) n=58 Participants Patients aged 18 and above at the time of informed consent. Mirdametinib (PD-0325901) capsule or dispersible tablet 2 mg/m\^2 (maximum dose of 4 mg) by mouth twice daily	Treatment Phase - Adult Cohort Mirdametinib (PD-0325901) - Self-Report Patients self-reported results aged 18 years and above at the time of informed consent. Mirdametinib (PD-0325901) capsule or dispersible tablet 2 mg/m\^2 (maximum dose of 4 mg) by mouth twice daily
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 months NA Explanation: NA Explanation: Not reached. Only less than 50% of the patients had events in the Pediatric cohort.	NA months NA Explanation: NA Explanation: Not reached. Only less than 50% of the patients had events in the Adult cohort.	—

OTHER_PRE_SPECIFIED outcome

Timeframe: Up to 24 months

For participants with a PN that is visible and amenable to photography, changes in visible tumor aspects will be evaluated by a centralized reviewer.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Up to 24 months

Measured in tumor biopsies in participants ≥ 18 years of age.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Completed only once through study completion

Population: The Full Analysis Set eligible for the instrument at baseline

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.

Outcome measures

Outcome measures
Measure	Treatment Phase - Pediatric Cohort Mirdametinib (PD-0325901) n=13 Participants Patients aged 2 to 17 years old at the time of informed consent. Mirdametinib (PD-0325901) capsule or dispersible tablet 2 mg/m\^2 (maximum dose of 4 mg) by mouth twice daily	Treatment Phase - Adult Cohort Mirdametinib (PD-0325901) n=17 Participants Patients aged 18 and above at the time of informed consent. Mirdametinib (PD-0325901) capsule or dispersible tablet 2 mg/m\^2 (maximum dose of 4 mg) by mouth twice daily	Treatment Phase - Adult Cohort Mirdametinib (PD-0325901) - Self-Report Patients self-reported results aged 18 years and above at the time of informed consent. Mirdametinib (PD-0325901) capsule or dispersible tablet 2 mg/m\^2 (maximum dose of 4 mg) by mouth twice daily
Acceptability of the Dispersible Tablet Formulation as Measured by the Pediatric Oral Medicine Acceptability Questionnaire (P-OMAQ) P-OMAQ-P	4.3 units on a scale Standard Deviation 0.87	NA units on a scale Standard Deviation NA Not eligible for this scale.	—
Acceptability of the Dispersible Tablet Formulation as Measured by the Pediatric Oral Medicine Acceptability Questionnaire (P-OMAQ) P-OMAQ-C	NA units on a scale Standard Deviation NA Not eligible for this scale.	4.56 units on a scale Standard Deviation 0.586	—

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline and Cycle 13 (1 cycle = 28 days), up to 12 months

Population: The Full Analysis Set patients eligible for this instrument at baseline.

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.

Outcome measures

Outcome measures
Measure	Treatment Phase - Pediatric Cohort Mirdametinib (PD-0325901) n=15 Participants Patients aged 2 to 17 years old at the time of informed consent. Mirdametinib (PD-0325901) capsule or dispersible tablet 2 mg/m\^2 (maximum dose of 4 mg) by mouth twice daily	Treatment Phase - Adult Cohort Mirdametinib (PD-0325901) n=23 Participants Patients aged 18 and above at the time of informed consent. Mirdametinib (PD-0325901) capsule or dispersible tablet 2 mg/m\^2 (maximum dose of 4 mg) by mouth twice daily	Treatment Phase - Adult Cohort Mirdametinib (PD-0325901) - Self-Report Patients self-reported results aged 18 years and above at the time of informed consent. Mirdametinib (PD-0325901) capsule or dispersible tablet 2 mg/m\^2 (maximum dose of 4 mg) by mouth twice daily
Change From Baseline in Localized Strength (Medical Research Council (MRC) Scale Grading) at Cycle 13.	0.3 units on a scale Standard Deviation 0.35	0.3 units on a scale Standard Deviation 0.46	—

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline and Cycle 13 (1 cycle = 28 days), up to 12 months

Population: The Full Analysis Set eligible for the instrument at baseline.

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.

Outcome measures

Outcome measures
Measure	Treatment Phase - Pediatric Cohort Mirdametinib (PD-0325901) n=7 Participants Patients aged 2 to 17 years old at the time of informed consent. Mirdametinib (PD-0325901) capsule or dispersible tablet 2 mg/m\^2 (maximum dose of 4 mg) by mouth twice daily	Treatment Phase - Adult Cohort Mirdametinib (PD-0325901) n=10 Participants Patients aged 18 and above at the time of informed consent. Mirdametinib (PD-0325901) capsule or dispersible tablet 2 mg/m\^2 (maximum dose of 4 mg) by mouth twice daily	Treatment Phase - Adult Cohort Mirdametinib (PD-0325901) - Self-Report Patients self-reported results aged 18 years and above at the time of informed consent. Mirdametinib (PD-0325901) capsule or dispersible tablet 2 mg/m\^2 (maximum dose of 4 mg) by mouth twice daily
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 T-score Standard Deviation 5.66	2.8 T-score Standard Deviation 5.67	—

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline and Cycle 13 (1 cycle = 28 days), up to 12 months

Population: The Full Analysis Set eligible for the instrument at baseline.

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.

Outcome measures

Outcome measures
Measure	Treatment Phase - Pediatric Cohort Mirdametinib (PD-0325901) n=3 Participants Patients aged 2 to 17 years old at the time of informed consent. Mirdametinib (PD-0325901) capsule or dispersible tablet 2 mg/m\^2 (maximum dose of 4 mg) by mouth twice daily	Treatment Phase - Adult Cohort Mirdametinib (PD-0325901) n=4 Participants Patients aged 18 and above at the time of informed consent. Mirdametinib (PD-0325901) capsule or dispersible tablet 2 mg/m\^2 (maximum dose of 4 mg) by mouth twice daily	Treatment Phase - Adult Cohort Mirdametinib (PD-0325901) - Self-Report Patients self-reported results aged 18 years and above at the time of informed consent. Mirdametinib (PD-0325901) capsule or dispersible tablet 2 mg/m\^2 (maximum dose of 4 mg) by mouth twice daily
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 T-score Standard Deviation 3.54	9.5 T-score Standard Deviation 3.54	—

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline and Cycle 13 (1 cycle = 28 days), up to 12 months

Population: The Full Analysis Set eligible for the instrument at baseline.

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.

Outcome measures

Outcome measures
Measure	Treatment Phase - Pediatric Cohort Mirdametinib (PD-0325901) n=23 Participants Patients aged 2 to 17 years old at the time of informed consent. Mirdametinib (PD-0325901) capsule or dispersible tablet 2 mg/m\^2 (maximum dose of 4 mg) by mouth twice daily	Treatment Phase - Adult Cohort Mirdametinib (PD-0325901) Patients aged 18 and above at the time of informed consent. Mirdametinib (PD-0325901) capsule or dispersible tablet 2 mg/m\^2 (maximum dose of 4 mg) by mouth twice daily	Treatment Phase - Adult Cohort Mirdametinib (PD-0325901) - Self-Report Patients self-reported results aged 18 years and above at the time of informed consent. Mirdametinib (PD-0325901) capsule or dispersible tablet 2 mg/m\^2 (maximum dose of 4 mg) by mouth twice daily
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 T-score Standard Deviation 9.447	—	—

Adverse Events

Treatment Phase - Pediatric Cohort Mirdametinib (PD-0325901)

Serious events: 8 serious events

Other events: 56 other events

Deaths: 0 deaths

Treatment Phase - Adult Cohort Mirdametinib (PD-0325901)

Serious events: 10 serious events

Other events: 57 other events

Deaths: 1 deaths

Serious adverse events

Other adverse events

Additional Information

Head of Clinical Operations

SpringWorks Therapeutics, Inc.

Phone: 8772794870

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: LTE60