The FDA approved mirdametinib (Gomekli) for adults and children 2 years and older with neurofibromatosis type 1 (NF1) and symptomatic plexiform neurofibromas (PN) that are not resectable surgically.
Approval resulted from the phase 2 ReNeu trial (NCT03962543), which found a confirmed overall response rate (ORR) of 41% (95% CI, 29%-55%) in 58 adults and 52% (95% CI, 38%-65%) in 56 children. The importance of the approval was noted by Dr. Christopher L. Moertel of the University of Minnesota, specifically for adults, who had no FDA-approved therapy for NF1-associated PN.
ReNeu was an open-label, multicenter trial enrolling patients with inoperable NF1-PN leading to significant comorbidity. The patients received mirdametinib 2 mg/m² twice daily (max 4 mg) every 3 weeks-on/1-week-off. Confirmed ORR by ≥20% reduction in tumor volume per MRI was the primary endpoint. The secondary endpoints were duration of response (DOR), patient-reported outcomes, and safety.
Additional data presented at the 2024 ASCO Annual Meeting reported median tumor volume reduction of –41% in adults, of whom 62% had deep responses (≥50% reduction). Median time to response (TTR) was 7.8 months, and the median duration of treatment (DOT) was 22 months, with the median duration of response (DOR) not reached. In pediatric patients, median best tumor reduction was –42%, of whom 52% had deep responses. Pediatric TTR, DOT, and DOR approximated those of adults.
Mirdametinib also increased pain severity and health-related quality of life. Treatment was tolerable overall, with any-grade treatment-related adverse events (TRAEs) in 98% of adults and 95% of pediatric patients. Grade 3 or higher TRAEs were experienced in 16% and 25%, respectively. Rash, diarrhea, nausea, musculoskeletal pain, vomiting, and fatigue were the most common side effects in adults, and rash, diarrhea, abdominal pain, vomiting, headache, and left ventricular dysfunction in children. Serious TRAEs were uncommon, occurring in 2% of adults and none in children.
This approval provides much-needed therapy for NF1 patients with inoperable PN for tumor burden and quality-of-life concerns.
Source: www.onclive.com/view/fda-approves-mirdametinib-for-nf1-associated-plexiform-neurofibromas
