FDA Grants Approval to Selumetinib for Adults With NF1 and Symptomatic, Inoperable Plexiform Neurofibromas
Key Clinical Summary
- Population and Setting: Adults (≥18 y) with neurofibromatosis type 1 (NF1) and symptomatic, inoperable plexiform neurofibromas (PN); global, randomized, double-blind phase 3 KOMET trial (NCT04924608).
- Efficacy: Selumetinib achieved 20% confirmed ORR (95% CI, 11–31) vs 5% with placebo (P = .011); 86% of responders maintained response ≥6 mo.
- Dosing and Safety: 25 mg/m² PO BID until progression/toxicity; AEs consistent with prior use. Label warnings include cardiac, ocular, GI, skin, CPK, vitamin E/bleeding, and embryo-fetal toxicities.
On November 19, 2025, the US Food and Drug Administration (FDA) approved selumetinib for adult patients with neurofibromatosis type 1 (NF1) who have symptomatic, inoperable plexiform neurofibromas (PN). This expands the indication for selumetinib, which was previously approved for pediatric patients aged ≥1 year with the same condition.
Approval was based on findings from the KOMET trial (NCT04924608), a global, randomized, multicenter, double-blind, placebo-controlled study. Eligible adults (≥18 years) with NF1 and symptomatic, inoperable PN—defined as tumors that could not be safely resected without substantial morbidity—were randomized 1:1 to receive selumetinib or placebo twice daily for 12 cycles.
The primary endpoint was confirmed overall response rate (ORR) by the end of Cycle 16, assessed by independent central review per the Response Evaluation in Neurofibromatosis and Schwannomatosis criteria. Duration of response (DOR) was a key secondary endpoint.
At analysis, confirmed ORR was 20% (95% CI, 11 to 31) in the selumetinib arm versus 5% (95% CI, 2 to 13) with placebo (P = .011). Among responders, 86% in the selumetinib arm maintained a response for ≥6 months. Adverse events were consistent with the known selumetinib safety profile.
The recommended adult dose of selumetinib is 25 mg/m² orally twice daily, continued until disease progression or unacceptable toxicity.
The prescribing information includes warnings and precautions for left ventricular dysfunction, ocular toxicity, gastrointestinal toxicity, skin toxicity, increased creatine phosphokinase, elevated vitamin E levels and bleeding risk, and embryo-fetal toxicity.
Source:
US Food and Drug Administration. Accessed November 19, 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-selumetinib-adults-neurofibromatosis-type-1-symptomatic-inoperable-plexiform
