FDA Approves Selumetinib for Adult NF1-Associated Plexiform Neurofibromas

The FDA has approved selumetinib (Koselugo) for the treatment of adult patients with neurofibromatosis type 1 (NF1) who have symptomatic, inoperable plexiform neurofibromas (PN).1

The regulatory decision was supported by data from the phase 3 KOMET trial (NCT04924608), which demonstrated that patients treated with selumetinib experienced a confirmed overall response rate (ORR) of 20% (95% CI, 11%-31%) vs 5% (95% CI, 2%-13%) for patients treated with placebo (P = .011). Notably, the 6-month duration of response rate was 86% in the selumetinib arm.

In September 2025, the FDA also approved selumetinib granules and capsules for the treatment of pediatric patients 1 year of age and older with NF1 who have symptomatic, inoperable PNs.2

What data were previously presented from KOMET?

At the 2025 ASCO Annual Meeting, investigators presented findings from the primary analysis of KOMET, an international, randomized, placebo-controlled phase 3 study that enrolled patients at least 18 years of age with NF1 and symptomatic, inoperable PNs who were naive to MEK inhibitors, had a baseline score of at least 1 on the PAINS-pNF scale, and were on stable chronic pain medication at baseline.3

Patients were randomly assigned 1:1 to receive selumetinib at 25 mg/m2 twice per day or placebo for the first 12 cycles. After 12 cycles, the trial transitioned to an open-label treatment period, where patients in both arms received selumetinib on the same schedule for 12 additional cycles. Early crossover from the placebo arm was permitted in the case of MRI-confirmed disease progression.

ORR at the end of cycle 16 served as the trial's primary end point. Change in chronic target PN pain intensity at the end of cycle 12 and change in health-related quality of life at the end of cycle 12 were key secondary end points, along with safety.

Findings from the primary analysis showed the ORR at week 16 was 20% (95% CI, 11.2%-30.9%) in the selumetinib arm (n = 71) compared with 5% (9%% CI, 1.5%-13.3%) in the placebo arm (n = 74; P = .0112).

Investigators also reported consistent improvement in chronic pain after treatment with selumetinib across populations, although statistical significance was not reached for the subgroup of patients with a baseline pain threshold of at least 3 per the PAINS-pNF scale (P = .070).

Additionally, 27% of patients in the selumetinib arm experienced a decrease in chronic pain medication use compared with 14% in the placebo arm.

What safety data were reported from the KOMET trial?

Findings presented at ASCO 2025 also showed that the most common any-grade treatment-related adverse effects reported in at least 10% of patients during the randomized portion of the trial included dermatitis acneiform (selumetinib arm, 59%; placebo arm, 8%), increased blood creatine phosphokinase levels (42%; 3%), diarrhea (28%; 12%), nausea (18%; 11%), increased aspartate aminotransferase levels (17%; 3%), increased alanine aminotransferase levels (16%; 3%), rash (16%; 4%), alopecia (16%; 10%), vomiting (16%; 4%), peripheral edima (14%; 1%), fatigue (14%; 10%), dry skine (14%; 5%), and paronychia (10%; 4%).

The prescribing information for selumetinib includes warnings and precautions for left ventricular dysfunction, ocular toxicity, gastrointestinal toxicity, skin toxicity, increased creatine phosphokinase levels, increased vitamin E levels, and increased risk of bleeding.1

For adult patients with NF1-associated symptomatic, inoperable PNs, selumetinib is recommended at a dose of 25 mg/m2 twice per day until disease progression or unacceptable toxicity.

References

1. FDA approves selumetinib for adults with neurofibromatosis type 1 with symptomatic, inoperable plexiform neurofibromas. FDA. November 19, 2025. Accessed November 19, 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-selumetinib-adults-neurofibromatosis-type-1-symptomatic-inoperable-plexiform
2. FDA approves selumetinib for pediatric patients 1 year of age and older with neurofibromatosis type 1 with symptomatic, inoperable plexiform neurofibromas. FDA. September 10, 2025. Accessed November 19, 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-selumetinib-pediatric-patients-1-year-age-and-older-neurofibromatosis-type-1
3. Chen A, O'Sullivan Coyne G, Wolters P, et al. Efficacy and safety of selumetinib in adults with neurofibromatosis type 1 (NF1) and symptomatic, inoperable plexiform neurofibroma (PN): Primary analysis of KOMET (NCT04924608), a phase 3, international, randomized, placebo-controlled study. J Clin Oncol. 2025;43(suppl 16):3014. doi:10.1200/JCO.2025.43.16_suppl.3014