A manageable safety profile in adults
Actor portrayal.
The majority of adverse reactions in ReNeu were mild to moderate1
Adverse reactions (≥20%) in adult patients who received GOMEKLI (n=58)1
All grades
Grade 3 or 4*
Skin and subcutaneous tissue disorders
Rash†
10%
Gastrointestinal disorders
59%
0%
Nausea
52%
0%
Vomiting
38%
0%
24%
3%
Musculoskeletal and connective tissue disorders
Musculoskeletal painǁ
41%
5%
General disorders and administration site conditions
Fatigue
29%
2%
Infections and infestations
22%
5%
Nervous system disorders
21%
0%
Low rates of severe (Grade 3) reactions were observed with GOMEKLI.1
GOMEKLI has no contraindications.1
*All reactions were Grade 3 except one fatal case of COVID-19 in an adult.
†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.
‡Diarrhea includes frequent bowel movements.
§Abdominal pain includes upper abdominal pain, gastrointestinal pain, and abdominal discomfort.
ǁMusculoskeletal pain includes noncardiac chest pain, back pain, pain in extremity, neck pain, musculoskeletal chest pain, myalgia, arthralgia, and bone pain.
¶Includes one fatal case in an adult.
#Peripheral neuropathy includes paresthesia, hypoesthesia, neuralgia, and peripheral sensory neuropathy.
Laboratory abnormalities
Select laboratory abnormalities (≥15%) that worsened from baseline in adult patients who received GOMEKLI in ReNeu (n=58)1,**,††
All grades
Chemistry
Increased creatine phosphokinase
55%
4%
Increased triglycerides
29%
0%
23%
0%
Increased cholesterol
23%
0%
Increased aspartate
aminotransferase (AST)
18%
0%
Hematology
Decreased hemoglobin
21%
0%
Decreased lymphocytes
16%
0%
**The denominator used to calculate the rate was 56 based on the number of patients with a baseline value and at least 1 posttreatment value.
††Graded per NCI-CTCAE version 5.0.
‡‡No Grade 5 laboratory abnormalities were reported in the ReNeu study.
§§Calcium corrected for albumin (mmol/L).
CTCAE=Common Terminology Criteria for Adverse Events; NCI=National Cancer Institute.
Additional information on select adverse reactions
- Rash (all grades) was reported in 90% of adult patients and 10% had Grade 3 rash1
- 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 rash1
- Supportive care should be initiated at first signs of dermatologic adverse reactions. GOMEKLI should be withheld, dose reduced, or permanently discontinued based on severity of adverse reaction1
- The GI adverse reactions reported in ≥20% of patients in the adult cohort were diarrhea (59%), nausea (52%), vomiting (38%), and abdominal pain (24%)1
- There were no Grade ≥3 cases of diarrhea, nausea, or vomiting reported; 3% of patients had Grade 3 abdominal pain1
Diarrhea
71% (24/34)
Nausea
80% (24/30)
Vomiting
55% (12/22)
Abdominal pain
43% (6/14)
GI=gastrointestinal.
- 3 patients in the adult cohort of ReNeu reported blurred vision3
- Retinal pigment epithelium detachment (RPED) occurred in 1 adult patient1
-
Retinal vein occlusion (RVO) occurred in 2.7% of adult patients, including one Grade 3 case that was diagnosed on Day 130 and resulted in permanent treatment discontinuations1,2
- Confounding factors: Grade 3 RVO occurred 4 months after patient initiated hormonal contraception and 9 days after receiving a COVID-19 vaccination3
- No cases of uveitis, optic neuropathy, or retinopathy were reported2
- Conduct comprehensive ophthalmic assessments prior to initiating GOMEKLI, at regular intervals during treatment, and to evaluate any new or worsening visual changes such as blurred vision. Continue, withhold, reduce the dose, or permanently discontinue GOMEKLI based on severity of adverse reaction1
- GOMEKLI has not been studied in patients with a history of clinically significant cardiac disease or left ventricular ejection fraction (LVEF) <55% prior to initiation of treatment1
-
Decreased LVEF of 10% to <20% occurred in 16% of adult patients treated with GOMEKLI1
- Of the patients with decreased LVEF, 5 (9%) required dose interruption, 1 (1.7%) required a dose reduction, and 1 patient required permanent discontinuation of GOMEKLI
- The median time to first onset of decreased LVEF was 70 days1
- No cases of cardiac failure were reported in the adult cohort2
- Assess ejection fraction by echocardiogram prior to initiating treatment, every 3 months during the first year, then as clinically indicated thereafter. Withhold, reduce dose, or permanently discontinue GOMEKLI based on severity of adverse reaction1
Managing adverse reactions
Dose interruption, reduction, and discontinuation due to adverse reactions1
of patients had a dose reduction
Adverse reactions that required dose interruption in ≥5% of patients included left ventricular dysfunction and COVID-19. Adverse reactions that required dose reduction in ≥5% of patients included rash.
permanently discontinued treatment
Adverse reactions that resulted in permanent discontinuation of GOMEKLI in ≥1% of patients were rash, diarrhea, nausea, abdominal pain, alopecia, dry skin, left ventricular dysfunction, cough, wheezing, COVID-19, peripheral swelling, retinal vein occlusion, dizziness, and vomiting.
Dosing designed with patient needs in mind
Indication
GOMEKLI (mirdametinib) 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.
Important Safety Information
Warnings and Precautions
Ocular Toxicity: GOMEKLI can cause ocular toxicity including retinal vein occlusion (RVO), retinal pigment epithelium detachment (RPED), and blurred vision. In the adult pooled safety population, ocular toxicity occurred in 28% of patients treated with GOMEKLI: 21% were Grade 1, 5% were Grade 2 and 1.3% were Grade 3. RVO occurred in 2.7%, RPED occurred in 1.3%, and blurred vision occurred in 9% of adult patients. In the pediatric pooled safety population, ocular toxicity occurred in 19% of patients: 17% were Grade 1 and 1.7% were Grade 2. Conduct comprehensive ophthalmic assessments prior to initiating GOMEKLI, at regular intervals during treatment, and to evaluate any new or worsening visual changes such as blurred vision. Continue, withhold, reduce the dose, or permanently discontinue GOMEKLI as clinically indicated.
Left Ventricular Dysfunction: GOMEKLI can cause left ventricular dysfunction. GOMEKLI has not been studied in patients with a history of clinically significant cardiac disease or LVEF <55% prior to initiation of treatment. In the ReNeu study, decreased LVEF of 10 to <20% occurred in 16% of adult patients treated with GOMEKLI. Five patients (9%) required dose interruption, one patient (1.7%) required a dose reduction, and one patient required permanent discontinuation of GOMEKLI. The median time to first onset of decreased LVEF in adult patients was 70 days. Decreased LVEF of 10 to <20% occurred in 25%, and decreased LVEF of ≥20% occurred in 1.8% of pediatric patients treated with GOMEKLI. One patient (1.8%) required dose interruption of GOMEKLI. The median time to first onset of decreased LVEF in pediatric patients was 132 days. All patients with decreased LVEF were identified during routine echocardiography, and decreased LVEF resolved in 75% of patients. Before initiating GOMEKLI, assess ejection fraction (EF) by echocardiogram. Monitor EF every 3 months during the first year and then as clinically indicated. Withhold, reduce the dose, or permanently discontinue GOMEKLI based on severity of adverse reaction.
Dermatologic Adverse Reactions: GOMEKLI can cause dermatologic adverse reactions including rash. The most frequent rashes included dermatitis acneiform, rash, eczema, maculo-papular rash and pustular rash. In the pooled adult safety population, rash occurred in 92% of patients treated with GOMEKLI (37% were Grade 2 and 8% were Grade 3) and resulted in permanent discontinuation in 11% of patients. In the pooled pediatric safety population, rash occurred in 72% of patients treated with GOMEKLI (22% were Grade 2 and 3.4% were Grade 3) and resulted in permanent discontinuation in 3.4% of patients. Initiate supportive care at first signs of dermatologic adverse reactions. Withhold, reduce the dose, or permanently discontinue GOMEKLI based on severity of adverse reaction.
Embryo-Fetal Toxicity: GOMEKLI can cause fetal harm when administered to a pregnant woman. Verify the pregnancy status of females of reproductive potential prior to the initiation of GOMEKLI. Advise pregnant women and females of reproductive potential of the potential risk to a fetus. Also advise patients to use effective contraception during treatment with GOMEKLI and for 6 weeks after the last dose (females) or 3 months after the last dose (males).Adverse Reactions
The most common adverse reactions (>25%) in adult patients were rash (90%), diarrhea (59%), nausea (52%), musculoskeletal pain (41%), vomiting (38%), and fatigue (29%). Serious adverse reactions occurred in 17% of adult patients who received GOMEKLI. The most common Grade 3 or 4 laboratory abnormality (>2%) was increased creatine phosphokinase.
The most common adverse reactions (>25%) in pediatric patients were rash (73%), diarrhea (55%), musculoskeletal pain (41%), abdominal pain (39%), vomiting (39%), headache (34%), paronychia (32%), left ventricular dysfunction (27%), and nausea (27%). Serious adverse reactions occurred in 14% of pediatric patients who received GOMEKLI. The most common Grade 3 or 4 laboratory abnormalities (>2%) were decreased neutrophil count and increased creatine phosphokinase.Use in Specific Populations
Indication
References
- GOMEKLI. Prescribing Information. SpringWorks Therapeutics, Inc.
- Data on file: SpringWorks Therapeutics, Inc.
- Moertel CL, Hirbe AC, Shuhaiber HH, et al. ReNeu: a pivotal, phase IIb trial of mirdametinib in adults and children with symptomatic neurofibromatosis type 1-associated plexiform neurofibroma. J Clin Oncol. Published online November 8, 2024. doi.org/10.1200/JCO.24.01034