Drug Trials Snapshots: GOMEKLI
HOW TO USE THIS SNAPSHOT
The information provided in Snapshots highlights who participated in the key clinical trials that supported the original FDA approval of this drug, and whether there were differences among sex, race, age, and ethnic groups. The “MORE INFO” bar shows more detailed, technical content for each section. The Snapshot is intended as one tool for consumers to use when discussing the risks and benefits of the drugs.
LIMITATIONS OF THIS SNAPSHOT
Do not rely on Snapshots to make decisions regarding medical care. Always speak to your healthcare provider about the benefits and risks of a drug.
Some of the information in this Snapshot is for presentation purposes and does not represent the approved conditions of use of this drug. Refer to the GOMEKLI Prescribing Information for all of the approved conditions of use of this drug (e.g., indication(s), population(s), dosing regimen(s), safety information).
Snapshots are limited to the information available at the time of the original approval of the drug and do not provide information on who participated in clinical trials that supported later approvals for additional uses of the drug (if applicable).
GOMEKLI (mirdametinib)
(Go-mek-lee)
SpringWorks Therapeutics, Inc.
Approval date: February 11, 2025
DRUG TRIALS SNAPSHOT SUMMARY:
What is the drug for?
GOMEKLI is a prescription medicine that is used to treat adults and children 2 years of age and older with neurofibromatosis type 1 (NF1) who have plexiform neurofibromas that cause symptoms and cannot be completely removed by surgery.
How is this drug used?
GOMEKLI comes in 2 different dosage forms, GOMEKLI capsules and GOMEKLI tablets for oral suspension. GOMEKLI is taken twice a day by mouth with or without food, about 12 hours apart, for 21 days, followed by 7 days off treatment, to complete a 28-day treatment cycle. The number of treatment cycles will be decided by the healthcare provider.
Who participated in the clinical trials?
The FDA approved GOMEKLI based on evidence from a clinical trial (ReNeu; NCT03962543) that included 114 patients at least 2 years of age or older with neurofibromatosis type 1 (NF1) who have plexiform neurofibromas that cause symptoms and cannot be completely removed by surgery. The trial was conducted at 50 sites in the United States.
The number of patients representing efficacy findings differs from the number of patients representing safety due to different pools of study participants analyzed for efficacy and safety.
How were the trials designed?
GOMEKLI was evaluated in a clinical trial of 58 adults (age 18 and older) and 56 pediatric patients (age 2-17) with neurofibromatosis type 1 (NF1) who have plexiform neurofibromas (PN) that cause symptoms and cannot be completely removed by surgery. Patients received GOMEKLI twice a day for the first 21 days of a 28-day treatment cycle. Treatment continued until disease progression or unacceptable side effects. The dose of GOMEKLI was based on the patient’s weight and height (body surface area). The trial measured the percent of patients that experienced partial shrinkage (20% or more) or complete disappearance (100%) of their PN while receiving GOMEKLI, which is also known as the overall response rate. The overall response rate was confirmed, which measures how many trial participants saw their PN shrink by 20% or more from their initial scan in at least two back-to-back scans.
How were the trials designed?
The ReNeu study (NCT03962543), a multicenter clinical trial, evaluated the efficacy and safety of GOMEKLI in 114 adult and pediatric patients with symptomatic, inoperable neurofibromatosis type 1 (NF1) associated plexiform neurofibromas (PN) causing significant morbidity. An inoperable PN was defined as a PN that cannot be completely surgically removed without risk for serious complications due to encasement of or close proximity to vital structures, invasiveness, or high vascularity of the PN. Patients received GOMEKLI 2 mg/m2 orally twice daily for the first 21 days of each 28-day cycle until disease progression or unacceptable toxicity.
The major efficacy outcome measure was confirmed overall response rate (ORR), defined as the percentage of patients with complete response (disappearance of the target PN) or partial response (≥20% reduction in PN volume from baseline). Responses were assessed by blinded independent central review (BICR) using volumetric magnetic resonance imaging (MRI) analysis per Response Evaluation in Neurofibromatosis and Schwannomatosis (REiNS) criteria modified to be confirmed at a subsequent tumor assessment within 2 to 6 months during the 24-cycle treatment phase. A secondary efficacy outcome measure was duration of response for patients who achieved a confirmed response.
See CLINICAL TRIALS SECTION 14.1 of the Prescribing Information
DEMOGRAPHICS SNAPSHOT
Figure 1 summarizes how many male and female adult patients with neurofibromatosis type 1 who have symptomatic plexiform neurofibromas were enrolled in the clinical trial used to evaluate the efficacy of GOMEKLI.
Figure 1. Baseline Demographics by Sex (Adult population)
Source: Adapted from FDA Review
Figure 2 summarizes how many male and female of pediatric patients 2 to 17 years of age with neurofibromatosis type 1 who have symptomatic plexiform neurofibromas were enrolled in the clinical trial used to evaluate the efficacy of GOMEKLI.
Figure 2. Baseline Demographics by Sex (Pediatric population)
Source: Adapted from FDA Review
Figure 3 summarizes the percentage adult patients with neurofibromatosis type 1 who have symptomatic plexiform neurofibromas by race enrolled in the clinical trial used to evaluate the efficacy of GOMEKLI.
Figure 3. Baseline Demographics by Race (Adult population)
Source: Adapted from FDA Review
Figure 4 summarizes the percentage pediatric patients with neurofibromatosis type 1 who have symptomatic plexiform neurofibromas by race enrolled in the clinical trial used to evaluate the efficacy of GOMEKLI.
Figure 4. Baseline Demographics by Race (Pediatric population)
Source: Adapted from FDA Review
Figure 5 summarizes the percentage of patients with neurofibromatosis type 1 who have symptomatic plexiform neurofibromas by age enrolled in the clinical trial used to evaluate the efficacy of GOMEKLI.
Figure 5. Baseline Demographics by Age
Source: Adapted from FDA Review
Figure 6 summarizes the percentage of adult patients with neurofibromatosis type 1 who have symptomatic plexiform neurofibromas by ethnicity enrolled in the clinical trial used to evaluate the efficacy of GOMEKLI.
Figure 6. Baseline Demographics by Ethnicity (Adult population)
Source: Adapted from FDA Review
Figure 7 summarizes the percentage of pediatric patients with neurofibromatosis type 1 who have symptomatic plexiform neurofibromas by ethnicity enrolled in the clinical trial used to evaluate the efficacy of GOMEKLI.
Figure 7. Baseline Demographics by Ethnicity (Pediatric population)
Source: Adapted from FDA Review
Who participated in the trials?
Table 1. Baseline Demographics of the Trial by Age, Race, Sex, and Ethnicity
| Demographic Parameter | Adult (N=58) n (%) | Pediatric (N=56) n (%) | Total (N=114) n (%) |
|---|---|---|---|
| Sex | |||
| Male | 21 (36) | 26 (46) | 47 (41) |
| Female | 37 (64) | 30 (54) | 67 (59) |
| Race | |||
| Black or African American | 5 (9) | 11 (20) | 16 (14) |
| White | 49 (85) | 37 (66) | 86 (75) |
| Asian | 2 (3) | 2 (4) | 4 (4) |
| American Indian or Alaska Native | 0 | 1 (2) | 1 (1) |
| Other | 2 (3) | 5 (9) | 7 (6) |
| Age group, years | |||
| 2 to 11 | N/A | 32 (57) | 32 (28) |
| 12 to 17 | N/A | 24 (43) | 24 (21) |
| 18 to 64 | 56 (97) | N/A | 56 (49) |
| ≥65 | 2 (3) | N/A | 2 (2) |
| Ethnicity | |||
| Hispanic or Latino | 1 (2) | 8 (14) | 9 (8) |
| Not Hispanic or Latino | 52 (90) | 44 (79) | 96 (84) |
| Unknown | 5 (9) | 4 (7) | 9 (8) |
Source: Adapted from FDA Review
What are the benefits of this drug?
In this trial, 41% (24 out of 58) of adult participants treated with GOMEKLI saw their plexiform neurofibromas shrink by at least 20%. Out of the 24 adult participants that saw their tumors shrink, 88% (21 out of 24) had tumor shrinkage for at least 12 months, while 50% (12 out of 24) had tumor shrinkage for at least 24 months.
In this trial, 52% (29 out of 56) of pediatric participants treated with GOMEKLI saw their plexiform neurofibromas shrink by at least 20%. Out of the 29 pediatric participants that saw their tumors shrink, 90% (26 out of 29) had tumor shrinkage for at least 12 months, while 48% (14 out of 29) had tumor shrinkage for at least 24 months.
1 What are the benefits of this drug (results of trials used to assess efficacy)?
The table below summarizes efficacy results based on blinded independent central review (BICR) using volumetric MRI analysis. Response was determined per modified REiNS criteria.
Table 2. Efficacy Results by BICR from ReNeu per modified REiNS criteria
| Adult (N=58) | Pediatric (N=56) | |
| Confirmed Overall Response Ratea,b,c,n (%) | 24 (41%) | 29 (52%) |
| 95% CId | (29, 55) | (38, 65) |
| Duration of Response (DoR) | ||
| DoR ≥12 monthse | 21 (88%) | 26 (90%) |
| DoR ≥24 monthse | 12 (50%) | 14 (48%) |
a Confirmed overall response was defined as two consecutive assessments of PR or CR assessed within 2 to 6 months during the Treatment Phase.
b Patients who had no post-baseline MRI assessment or no confirmed overall response were treated as non-responders.
c All partial responses.
d Obtained using the Clopper-Pearson approach.
e Duration of response was assessed based on observed time.
See CLINICAL TRIALS SECTION 14.1 of the Prescribing Information
Were there any differences in how well the drug worked in clinical trials among sex, race and age?
- Sex: GOMEKLI worked similarly in men and women in the adult population. The observed effect of GOMEKLI was larger for females than males in the pediatric population. Because of limited data, this difference may be due to chance.
- Race: Differences among races could not be determined because of the small number of patients who were not White.
- Age: GOMEKLI worked similarly in pediatric and adult participants. The number of participants above 65 years of age was small; therefore, differences between this group and participants below 65 years of age could not be determined.
Were there any differences in how well the drug worked in clinical trials among sex, race and age groups?
Table 3. Efficacy Results by Sex, Race, Age, and Ethnicity in Adult and Pediatric Patients
| Adult (N=58) | Pediatric (N=56) | |||
|---|---|---|---|---|
| Demographic Subgroup | n | ORR (95% CI) | n | ORR (95% CI) |
| Sex | ||||
| Female | 37 | 40.5% (24.8, 57.9) | 30 | 56.7% (37.4, 74.5) |
| Male | 21 | 42.9% (21.8, 66.0) | 26 | 46.2% (26.6, 66.6) |
| Race | ||||
| American Indian or Alaska Native | 0 | 0 | 1 | 0 |
| Asian | 2 | 100% (15.8, 100) | 2 | 100% (15.8, 100) |
| Black or African American | 5 | 0 | 11 | 27.3% (6.0, 61.0) |
| White | 49 | 44.9% (30.7, 59.8) | 37 | 59.5% (42.1, 75.2) |
| Other | 2 | 0 | 5 | 40% (5.3, 85.3) |
| Age* | ||||
| 18 to <65 | 56 | 41.1% (28.1, 55.0) | N/A | N/A |
| >65 | 2 | 50.0% (1.3, 98.7) | N/A | N/A |
*Efficacy results for adult (age 18 years and older) and pediatric (age 2 to 17) age groups are presented in Table 2.
See FDA Primary Clinical/Multidisciplinary Review- Study Results Section (8.1.2 ) also may utilize the Statistical Review Integrated Review section e.g., Study Results
What are the possible side effects?
- Eye problems. GOMEKLI may cause eye problems that can lead to blindness.
- Heart problems. GOMEKLI may lower the amount of blood pumped by your heart, which is common in children during treatment with GOMEKLI and can also be severe.
- Skin problems. Skin rashes are common with GOMEKLI in both adults and children and can also be severe.
The most common side effects of GOMEKLI in adults include rash, diarrhea, nausea, muscle, joint, and bone pain, vomiting, and tiredness. The most common severe abnormal blood tests in adults include an increase enzyme called creatine phosphokinase (CPK).
The most common side effects of GOMEKLI in children include rash, diarrhea, muscle, joint, and bone pain, stomach (abdominal) pain, vomiting, headache, , swelling, or pain around the fingernails or toenails, left ventricular (heart) dysfunction, and nausea. The most common severe abnormal blood tests in children include decreased white blood cell (neutrophil) counts and increased CPK.
Clinically relevant adverse reactions that occurred in <20% of patients include:
- Skin and Subcutaneous Tissue Disorders: hair loss (alopecia), hair color changes
- Gastrointestinal Disorders: constipation
- Eye Disorders: retinal vein occlusion (RVO), retinal pigment epithelium detachment (RPED) and blurred vision
Refer to the Patient Information Sheet for more information.
What are the possible side effects (results of trials used to assess safety)?
Table 4: Adverse Reactions (≥20%) in Adult and Pediatric Patients with NF1- Associated PN Who Received GOMEKLI in ReNeu
| Adult N=58 | Pediatric N=56 | Total N=114 | ||||
|---|---|---|---|---|---|---|
| All Grades (%) | Grade 3 or 4a (%) | All Grades (%) | Grade 3 or 4a (%) | All Grades (%) | Grade3 or 4a (%) | |
| Skin and Subcutaneous Tissue Disorders | ||||||
| Rashb | 90 | 10 | 73 | 3.6 | 82 | 7 |
| Gastrointestinal Disorders | ||||||
| Diarrheac | 59 | 0 | 55 | 5 | 57 | 2.6 |
| Nausea | 52 | 0 | 27 | 0 | 40 | 0 |
| Vomiting | 38 | 0 | 39 | 0 | 39 | 0 |
| Abdominal Paind | 24 | 3.4 | 39 | 3.6 | 32 | 3.5 |
| Stomatitise | 5 | 0 | 20 | 0 | 12 | 0 |
| Musculoskeletal and Connective Tissue Disorders | ||||||
| Musculoskeletal Painf | 41 | 5 | 41 | 1.8 | 41 | 3.5 |
| General Disorders and Administration Site Conditions | ||||||
| Fatigue | 29 | 1.7 | 13 | 0 | 21 | 0.9 |
| Pyrexia | 7 | 0 | 20 | 0 | 13 | 0 |
| Infections and Infestations | ||||||
| COVID-19g | 22 | 5 | 25 | 0 | 24 | 2.6 |
| Paronychia | 1.7 | 0 | 32 | 0 | 17 | 0 |
| Upper Respiratory Tract Infection | 0 | 0 | 23 | 0 | 11 | 0 |
| Nervous System Disorders | ||||||
| Headacheh | 14 | 1.7 | 34 | 1.8 | 24 | 1.8 |
| Peripheral Neuropathyi | 21 | 0 | 3.6 | 0 | 12 | 0 |
| Cardiac Disorders | ||||||
| LeftVentricular Dysfunction | 16 | 0 | 27 | 1.8 | 21 | 0.9 |
| Respiratory, Thoracic and Mediastinal Disorders | ||||||
| Coughj | 9 | 0 | 21 | 0 | 15 | 0 |
a All reactions were Grade 3 except one fatal case of COVID-19 in an adult.
b Rash includes dermatitis acneiform, eczema, maculo-papular rash, pustular rash, dermatitis, erythematous rash, palmar-plantar erythrodysesthesia syndrome, exfoliative rash, skin exfoliation, pruritic rash, papule, papular rash and macular rash.
c Diarrhea includes frequent bowel movements.
d Abdominal pain includes upper abdominal pain, gastrointestinal pain and abdominal discomfort.
e Stomatitis includes mouth ulceration, aphthous ulcer.
f Musculoskeletal pain includes non-cardiac chest pain, back pain, pain in extremity, neck pain, musculoskeletal chest pain, myalgia, arthralgia, and bone pain.
g Includes one fatal case in an adult.
h Headache includes migraine.
i Peripheral neuropathy includes paresthesia, hypoesthesia, neuralgia, peripheral sensory neuropathy.
j Cough includes upper-airway cough syndrome.
Table 5: Select Laboratory Abnormalities (≥15%) that Worsened from Baseline in Adult and Pediatric Patients with NF1-Associated PN Who Received GOMEKLI in ReNeu
| Adulta | Pediatricb | Totalc | ||||
|---|---|---|---|---|---|---|
| Laboratory Abnormalityd,e | All Grades (%) | Grade 3 or 4d (%) | All Grades (%) | Grade 3 or 4d (%) | All Grades (%) | Grade 3 or 4d(%) |
| Chemistry | ||||||
| Increased Creatine Phosphokinase | 55 | 3.6 | 59 | 5 | 57 | 4.5 |
| Increased Triglycerides | 29 | 0 | 45 | 0 | 37 | 0 |
| Decreased Glucose | 5 | 0 | 36 | 1.8 | 21 | 0.9 |
| Decreased Calciumf | 23 | 0 | 20 | 0 | 21 | 0 |
| Increased Creatinine | 13 | 0 | 30 | 0 | 21 | 0 |
| Increased Cholesterol | 23 | 0 | 16 | 0 | 20 | 0 |
| Increased Alkaline Phosphatase | 13 | 0 | 29 | 0 | 21 | 0 |
| Decreased Bicarbonate | 11 | 0 | 21 | 0 | 16 | 0 |
| Increased Alanine Aminotransferase (ALT) | 9 | 0 | 21 | 0 | 15 | 0 |
| Increased Aspartate Aminotransferase (AST) | 18 | 0 | 9 | 0 | 13 | 0 |
| Hematology | ||||||
| Decreased Hemoglobin | 21 | 0 | 29 | 0 | 25 | 0 |
| Decreased Leukocytes | 7 | 0 | 40 | 0 | 23 | 0 |
| Decreased Neutrophils | 7 | 0 | 31 | 11 | 19 | 5 |
| Increased Lymphocytes | 7 | 0 | 27 | 0 | 17 | 0 |
| Decreased Lymphocytes | 16 | 0 | 1.8 | 0 | 9 | 0 |
a The denominator used to calculate the rate was 56 based on the number of patients with a baseline value and at least one post-treatment value.
b The denominator used to calculate the rate varied from 55 to 56 based on the number of patients with a baseline value and at least one post-treatment value.
c The denominator used to calculate the rate varied from 111 to 112 based on the number of patients with a baseline value and at least one post-treatment value.
d Graded per NCI-CTCAE version 5.0.
e No Grade 5 laboratory abnormalities were reported in the ReNeu study.
f Calcium corrected for albumin (mmol/L).
See the Highlights and Section 6 Adverse Reactions-6.1 Clinical Trials Experience of the Prescribing Information
Were there any differences in side effects among sex, race and age?
- Sex: The occurrence of side effects was similar in men and women.
- Race: Differences among races could not be determined because of the small number of patients who were not White.
- Age: Some TEAEs were reported more frequently among pediatric patients than adult patients, while some were reported more frequently among adult patients than pediatric patients. These are shown in Table 4. The number of participants above 65 years of age was small; therefore, differences between this group and participants below 65 years of age could not be determined.
Were there any differences in side effects of the clinical trials among sex, race and age groups?
Table 6. Side Effects by Sex, Race, Age, and Ethnicity, Safety Population
Adult N=58 | Pediatric N=56 | |||||
|---|---|---|---|---|---|---|
| Demographic Subgroup | Patients with TEAEs N (%) | Patients with TEAEs Grade ≥3 N (%) | Patients with Serious TEAEs N (%) |
Patients with TEAEs N (%) | Patients with TEAEs Grade ≥3 N (%) | Patients with Serious TEAEs N (%) |
| Sex | ||||||
| Female | 37 (100) | 12 (32) | 7 (19) | 30 (100) | 11 (37) | 2 (7) |
| Male | 21 (100) | 9 (43) | 3 (14) | 26 (100) | 11 (42) | 6 (23) |
| Race | ||||||
| White | 49 (100) | 18 (37) | 9 (18) | 37 (100) | 11 (30) | 3 (8) |
| Black or African American | 5 (100) | 1 (20) | 0 | 11 (100) | 8 (73) | 4 (36) |
| Asian | 2 (100) | 0 | 0 | 2 (100) | 0 | 0 |
| American Indian or Alaska Native | N/A | N/A | N/A | 1 (100) | 1 (100) | 0 |
| Other | 2 (100) | 2 (100) | 1 (50) | 5 (100) | 2 (40) | 1 (20) |
| Age | ||||||
| 2 to <18 years | N/A | N/A | N/A | 56 (100) | 22 (39) | 8 (14) |
| 18 to <65 years | 56 (100) | 19 (34) | 8 (14) | N/A | N/A | N/A |
| ≥65 years | 2 (100) | 2 (100) | 2 (100) | N/A | N/A | N/A |
N/A: Not Applicable; TEAE: Treatment-Emergent Adverse Event
GLOSSARY
CLINICAL TRIAL: Voluntary research studies conducted in people and designed to answer specific questions about the safety or effectiveness of drugs, vaccines, other therapies, or new ways of using existing treatments.
COMPARATOR: A previously available treatment or placebo used in clinical trials that is compared to the actual drug being tested.
EFFICACY: How well the drug achieves the desired response when it is taken as described in a controlled clinical setting, such as during a clinical trial.
PLACEBO: An inactive substance or “sugar pill” that looks the same as, and is given the same way as, an active drug or treatment being tested. The effects of the active drug or treatment are compared to the effects of the placebo.
SUBGROUP: A subset of the population studied in a clinical trial. Demographic subsets include sex, race, and age groups.