On November 19, 2025, the U.S. Food and Drug Administration (FDA) approved selumetinib (KOSELUGO, AstraZeneca) for adults with neurofibromatosis type 1 (NF1) who have symptomatic, inoperable plexiform neurofibromas (PN). Previously approved for pediatric patients aged 1 year and older, this marks the first adult indication expansion for NF1-associated tumors.
KOMET Trial Overview
The approval is based on the phase III KOMET trial (NCT04924608), a randomized, double-blind, placebo-controlled global study including 145 adult patients with NF1 and symptomatic, inoperable PN. Patients received 25 mg/m² selumetinib orally twice daily.
- Primary endpoint: Confirmed Overall Response Rate (ORR) at the end of Cycle 16
- Results: ORR 20% (95% CI: 11–31) for selumetinib vs 5% (95% CI: 2–13) for placebo (p=0.011)
- 86% of responders maintained duration of response ≥6 months.
Safety and Warnings
The label includes warnings for left ventricular dysfunction, ocular toxicity, gastrointestinal and skin toxicities, elevated CPK, vitamin E–related bleeding risk, and embryo-fetal toxicity. Adverse events were consistent with the known selumetinib safety profile observed in pediatric populations.
Clinical Significance
Selumetinib is the first MEK1/2 inhibitor shown to slow tumor growth in NF1-associated plexiform neurofibromas. The adult approval represents a major milestone in addressing a long-standing unmet need for NF1 patients and establishes selumetinib as a new therapeutic standard in this rare tumor space.
This article was produced by the Morningglorysciences Editorial Team.
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