Mirdametinib

Mirdametinib is an inhibitor of mitogen-activated protein kinase kinases 1 and 2 (MEK1/2). MEK1/2 proteins are upstream regulators of the extracellular signal-related kinase (ERK) pathway.

• GOMEKLI is indicated for the treatment of adult and pediatric patients 2 years of age and older with neurofibromatosis type 1 (NF1) who have symptomatic plexiform neurofibromas (PN) not amenable to complete resection [see Clinical Studies (14) ]. GOMEKLI is a kinase inhibitor indicated for the treatment of adult and pediatric patients 2 years of age and older with neurofibromatosis type 1 (NF1) who have symptomatic plexiform neurofibromas (PN) not amenable to complete resection.

• None. None.contraindicated

The recommended dosage of GOMEKLI is 2 mg/m 2 orally twice daily, with or without food, for the first 21 days of each 28-day cycle. Continue treatment with GOMEKLI until disease progression or unacceptable toxicity. ( 2 ) 2.1 Recommended Evaluation and Testing Before Initiating GOMEKLI Prior to administration of GOMEKLI: conduct comprehensive ophthalmic assessment [see Warnings and Precautions (5.1) ]. assess ejection fraction (EF) by echocardiogram [see Warnings and Precautions (5.2) ]. 2.2 GOMEKLI Dosage Form Overview GOMEKLI is available in 2 dosage forms: capsules or tablets for oral suspension. GOMEKLI capsules: must be swallowed whole, do not open, break or chew capsules. GOMEKLI tablets for oral suspension: can be swallowed whole or can be dispersed in drinking water and administered orally as a liquid [see Dosage and Administration (2.4) ]. 2.3 Recommended Dosage The recommended dosage of GOMEKLI is 2 mg/m 2 orally twice daily (approximately every 12 hours) with or without food for the first 21 days of each 28-day cycle. The maximum dose is 4 mg twice daily. Continue treatment with GOMEKLI until disease progression or unacceptable toxicity. The recommended dose of GOMEKLI is based on body surface area (BSA) as shown in Table 1. Table 1: Recommended Dosage for GOMEKLI Body Surface Area (m 2 ) * Recommended Dosage for Capsules or Tablets for Oral Suspension 0.40 to 0.69 1 mg twice daily 0.70 to 1.04 2 mg twice daily 1.05 to 1.49 3 mg twice daily ≥1.50 4 mg twice daily * The recommended dosage for patients with a BSA less than 0.40 m 2 has not been established.

Ocular Toxicity : Conduct comprehensive ophthalmic assessments prior to initiating GOMEKLI, at regular intervals during treatment and for new or worsening visual changes or blurred vision. Continue, withhold, reduce the dose, or permanently discontinue GOMEKLI based on severity. ( 5.1 ) Left Ventricular Dysfunction : Assess ejection fraction by echocardiogram prior to initiating GOMEKLI, every 3 months during the first year, then as clinically indicated thereafter. Withhold, reduce the dose, or permanently discontinue GOMEKLI based on severity. ( 5.2 ) Dermatologic Adverse Reactions : Initiate supportive care at first signs of dermatologic adverse reactions including rash. Withhold, reduce the dose, or permanently discontinue GOMEKLI based on severity. ( 5.3 ) Embryo-Fetal Toxicity : Can cause fetal harm. Advise patients of reproductive potential of the potential risk to a fetus and to use effective contraception. ( 5.4 ) 5.1 Ocular Toxicity GOMEKLI can cause ocular toxicity including retinal vein occlusion (RVO), retinal pigment epithelium detachment (RPED), and blurred vision. In the pooled safety population [see Adverse Reactions (6.1) ], ocular toxicity occurred in 25% of patients treated with GOMEKLI: 20% were Grade 1 reactions, 3.8% were Grade 2 reactions, and 0.8% were Grade 3 reactions. Adult Patients In the adult pooled safety population [see Adverse Reactions (6.1) ], ocular toxicity occurred in 28% of patients treated with GOMEKLI: 21% were Grade 1 reactions, 5% were Grade 2 reactions and 1.3% were Grade 3 reactions.

The following serious adverse reactions are described elsewhere in the labeling: Ocular Toxicity [see Warnings and Precautions (5.1) ] Left Ventricular Dysfunction [see Warnings and Precautions (5.2) ] Dermatologic Adverse Reactions [see Warnings and Precautions (5.3) ] Embryo-Fetal Toxicity [see Warnings and Precautions (5.4) ] Adults: The most common adverse reactions (>25%) were rash, diarrhea, nausea, musculoskeletal pain, vomiting, and fatigue. ( 6.1 ) The most common Grade 3 or 4 laboratory abnormality (>2%) was increased creatine phosphokinase. ( 6.1 ) Pediatric patients: The most common adverse reactions (>25%) were rash, diarrhea, musculoskeletal pain, abdominal pain, vomiting, headache, paronychia, left ventricular dysfunction, and nausea. ( 6.1 ) The most common Grade 3 or 4 laboratory abnormalities (>2%) were decreased neutrophil count and increased creatine phosphokinase. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact SpringWorks Therapeutics Inc. at 1-888-400-7989 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The pooled safety population described in the WARNINGS AND PRECAUTIONS reflects exposure to GOMEKLI in 133 patients (75 adults and 58 pediatric patients) in the ReNeu study [see Clinical Studies (14) ] (n=114) and Study NF-106 (n=19) [NCT-02096471].

Lactation: Advise not to breastfeed. ( 8.2 ) Infertility: May impair fertility in females. ( 8.3 ) 8.1 Pregnancy Risk Summary Based on findings from clinical trials, animal studies, and its mechanism of action [see Clinical Pharmacology (12.1) ] , GOMEKLI can cause fetal harm or loss of pregnancy when administered to a pregnant woman. In embryo-fetal development studies, oral administration of mirdametinib to pregnant rats and rabbits during the period of organogenesis caused embryo-fetal mortality, structural abnormalities and alterations to growth at doses that were approximately equivalent to the human clinical dose of 2 mg/m 2 twice daily based on BSA (see Data). Advise pregnant women of the potential risk to a fetus. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Data Human Data In ReNeu, a pregnancy reported 31 days after the last dose of GOMEKLI resulted in a first trimester spontaneous abortion. Animal Data In an embryo-fetal developmental toxicity study, mirdametinib was administered orally to pregnant rats during the period of organogenesis (gestation days 6 to 17) at doses of 0.3, 0.6, 3 or 5 mg/kg/day.

Metabolism

GOMEKLI pharmacokinetic parameters are summarized in Table 6. Table 6: Pharmacokinetic Parameters and Characteristics of Mirdametinib General Information Steady-state [mean (%CV)] Cmax Adult patients (≥18 years): 188 (52%) ng/mL Pediatric patients (2 to17 years): 191 (62%) ng/mL AUC Adult patients (≥18 years): 431 (43%) ng·h/mL Pediatric patients (2 to 17 years): 459 (46%) ng·h/mL Time to steady-state Approximately 6 days Accumulation ratio (AUC) [mean] 1.1 to 1.9 Absorption Tmax [median (min, max)] Tablet: 0.8 (0.4-3) hours post-dose Capsule: 1.1 (0-4) hours post-dose Absolute bioavailability…

• Feb 11, 2025NDANDA219379Springworks
• Feb 11, 2025NDANDA219389Springworks

1. 1Rash2331%
2. 2Nausea1520%
3. 3Fatigue1317%
4. 4Pain1216%
5. 5Acne1013%
6. 6Alopecia912%
7. 7Dermatitis Acneiform912%
8. 8Gastrointestinal Disorder811%
9. 9Dehydration79.3%
10. 10Diarrhoea79.3%
11. 11Abdominal Discomfort68.0%
12. 12Pruritus68.0%
13. 13Constipation56.7%
14. 14Eye Pain45.3%
15. 15Off Label Use45.3%

The 10 most recently updated of 28 ClinicalTrials.gov registrations naming Mirdametinib as an intervention. Registration is not evidence of efficacy or safety — reference crosswalk only.

• Combination Therapy (Mirdametinib and Sirolimus) for RAS Mutated Relapsed Refractory Multiple Myeloma
  Suspended · Phase 1 · Phase 2 · Interventional · 54 enrolled · National Cancer Institute (NCI)
  NCT06876142updated 2026-06-12
• Mirdametinib + BGB-3245 in Advanced Solid Tumors
  Terminated · Phase 1 · Phase 2 · Interventional · 23 enrolled · SpringWorks Therapeutics, Inc.
  NCT05580770updated 2026-06-11
• Phase 1/2 Study of Mirdametinib + Vinblastine for Newly Diagnosed/Previously Untreated PLGG + Activation of MAPK
  Recruiting · Phase 1 · Phase 2 · Interventional · 50 enrolled · St. Justine's Hospital
  NCT06666348updated 2026-06-11
• Testing the Effectiveness of the Anti-cancer Drug, Mirdametinib, in Treating Relapsed, Refractory Chronic Lymphocytic Leukemia
  Recruiting · Phase 2 · Interventional · 20 enrolled · National Cancer Institute (NCI)
  NCT07061951updated 2026-06-01
• A Window of Opportunity Trial of Mirdametinib Plus Vorinostat for NF1 Associated, H3K27 Trimethylation Deficient Malignant Peripheral Nerve Sheath Tumor [MPNST]
  Recruiting · Early phase 1 · Interventional · 8 enrolled · University of Minnesota
  NCT06693284updated 2026-05-29
• A Study of Mirdametinib in Combination With Palbociclib in People With Liposarcoma
  Recruiting · Phase 1 · Phase 2 · Interventional · 54 enrolled · Memorial Sloan Kettering Cancer Center
  NCT06843967updated 2026-05-22
• A Study of Mirdametinib in People With Central Nervous System Tumors
  Recruiting · Phase 1 · Phase 2 · Interventional · 26 enrolled · Memorial Sloan Kettering Cancer Center
  NCT07539441updated 2026-05-13
• To Assess the Enzyme Inducing Effects of Carbamazepine on the PK of Mirdametinib in Healthy Participants
  Completed · Phase 1 · Interventional · 36 enrolled · SpringWorks Therapeutics, Inc., a healthcare company of Merck KGaA, Darmstadt, Germany
  NCT07279233updated 2026-05-08
• Effect of Hepatic Impairment on the Pharmacokinetics of Mirdametinib
  Recruiting · Phase 1 · Interventional · 32 enrolled · SpringWorks Therapeutics, Inc., a healthcare company of Merck KGaA, Darmstadt, Germany
  NCT06997276updated 2026-05-08
• Individual Patient Compassionate Use of Mirdametinib
  Available · Expanded access · SpringWorks Therapeutics, Inc., a healthcare company of Merck KGaA, Darmstadt, Germany
  NCT05028166updated 2026-05-08

Frequently asked questions

How does Mirdametinib work?

Mirdametinib is an inhibitor of mitogen-activated protein kinase kinases 1 and 2 (MEK1/2). MEK1/2 proteins are upstream regulators of the extracellular signal-related kinase (ERK) pathway.

What is Mirdametinib used for?

According to FDA labeling, Mirdametinib carries indications including: GOMEKLI is indicated for the treatment of adult and pediatric patients 2 years of age and older with neurofibromatosis type 1 (NF1) who have symptomatic plexiform neurofibromas (PN) not amenable to complete resection [see Clinical Studies (14) ]. GOMEKLI is a kinase inhibitor indicated for the treatment of adult and pediatric patients 2 years of age and older with neurofibromatosis type 1 (NF1) who have symptomatic plexiform neurofibromas (PN) not amenable to complete resection.. This is a reference summary of labeled uses, not medical advice or a treatment recommendation.

What class of drug is Mirdametinib?

Mirdametinib is classified as Mitogen-activated protein kinase (MEK) inhibitors, Kinase Inhibitor, Mitogen-Activated Protein Kinase Kinase 1 Inhibitors, Mitogen-Activated Protein Kinase Kinase 2 Inhibitors, Cellular Proliferation Alteration.

What are the brand names for Mirdametinib?

Mirdametinib is marketed under brand names including Gomekli.

What are the contraindications for Mirdametinib?

Mirdametinib labeling lists contraindications including: None. None.. Always consult the full prescribing information and a clinician.