Koselugo (selumetinib)

P1, N=24, Active, not recruiting, AstraZeneca | Trial completion date: Jan 2026 --> Apr 2028

Following selumetinib therapy, the RAH showed measurable reduction in size (from 5.51 × 10.69 mm to 5.46 × 5.23 mm on ocular ultrasonography) and resolution of associated retinal detachment This case highlights a novel observation of selumetinib-associated RAH regression in an a patient with NF1. Although selumetinib was not prescribed for ocular disease, these findings suggest a potential off-target benefit and support further exploration of mitogen-activated protein kinase inhibitors in managing vision-threatening RAH in NF1.

Due to heterogeneous manifestations and variable disease trajectories, there is no standardized treatment algorithm. Integrating molecular diagnostics, targeted therapies, and multidisciplinary care is crucial for personalized and effective long - term management of those with this genetic disorder.

P3, N=165, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Dec 2030 --> Dec 2027 | Trial primary completion date: Dec 2030 --> Dec 2027

In pediatric NF1 patients treated with selumetinib, fracture and impaired bone healing may be rare side effects, especially during limb lengthening. These findings highlight the importance of closely monitoring bone health in NF1 patients on MEK inhibitors, particularly when undergoing orthopedic procedures.

While mitogen-activated protein kinase kinase (MEK) inhibitors, selumetinib and mirdametinib, can reduce tumor volume, surgical resection remains the primary treatment for immediate debulking and symptom relief. These results provide the first evidence that ECM stiffening, such as that arising from postsurgical remodeling, directly drives pNF1 progression and therapeutic resistance. Our findings highlight mechanobiology as a key regulator of tumor behavior and support targeting ECM mechanics to improve clinical outcomes in NF1 patients.

P1, N=344, Active, not recruiting, AstraZeneca | Trial completion date: Dec 2025 --> Dec 2026

Pharmacological inhibition of FAK with single agent VS-4718 did not significantly reduce macroscopic tumor volume; however, its use in combination with the mitogen-activated protein kinase kinase (MEK) inhibitor selumetinib resulted in both a significant reduction in tumor volume and the preservation of dorsal root ganglion architecture. Our findings establish a critical role for FAK in schwannoma development and provide rationale for evaluation of combination FAK plus MEK inhibition in future clinical trials for NF2-associated SWN.

IFNG, PTPN6, SLC38A1, and SOCS1 may serve as potential biomarkers of poor prognosis in SKCM patients. These genes demonstrate predictive value for immunotherapy response and drug sensitivity, particularly indicating susceptibility to selumetinib treatment, and therefore show substantial potential for clinical translation.

Selumetinib granule formulation (25 mg/m2 dose equivalent, twice a day) had comparable exposure to selumetinib capsule formulation, and was palatable with a manageable safety profile. Selumetinib granule formulation is potentially suitable for young children with NF1-PN who cannot swallow capsules.

P2, N=25, Active, not recruiting, Dana-Farber Cancer Institute | Trial completion date: Jun 2026 --> Dec 2026 | Trial primary completion date: Dec 2025 --> Jun 2026

P2, N=1376, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: May 2026 --> Jan 2027