Koselugo (selumetinib)

CCNJL has the potential to act as a valuable prognostic indicator and immunotherapy target in CHOL. Its expression pattern and associations with clinical outcomes, immune characteristics, and drug sensitivity highlight its potential for improving diagnostic and therapeutic approaches. Future research should focus on elucidating the underlying mechanisms and validating these findings in larger cohorts.

We evaluated RAS/MAPK targeting using the MEK1/2 inhibitor selumetinib in combination with the menin inhibitor revumenib. Our preclinical study suggests a potential targeted treatment combination for KMT2A-r and RAS pathway mutant leukemia, but one which will require further optimization. COG completed clinical trials AAML03P1, AAML0531, AAML1031 and C2961.

Several recent and ongoing clinical trials have demonstrated both the safety and efficacy of MEK inhibitors for plexiform neurofibroma (PN) and low-grade glioma, with the phase 1/2 study of selumetinib supporting the first regulatory approval of a medical therapy for PN. The relative successes of MEK inhibitors for the treatment of PN have created an exciting and hopeful era for patients, families, and clinicians alike providing the momentum and significant interest in expanding the use of MEK inhibitors across tumor types in NF1. Herein, we review the landscape of past and present clinical trials and supporting evidence for the use of MEK inhibitors in NF1-associated tumors.

Early response to selumetinib therapy is achieved faster in children than in adolescents. Selumetinib is generally well tolerated in both age groups.

P2, N=423, Completed, University of Birmingham | Active, not recruiting --> Completed

Redifferentiation approaches using MAPK pathway inhibitors such as selumetinib and dabrafenib can restore iodine uptake in selected patients, although the overall clinical applicability of these strategies remains under evaluation. A better understanding of these mechanisms may support improved biologic stratification and more selective therapeutic decision-making in radioiodine-refractory DTC.

Higher selumetinib exposure appears to be associated with treatment-related adverse effects in pediatric NF1 patients. These findings support the potential role of TDM in optimizing selumetinib dosing and provide a preliminary therapeutic AUC range for individualized treatment strategies. Larger multicenter studies are needed to validate these results and refine exposure-guided dosing approaches.

Selumetinib treatment was associated with a significant, consistent, and durable decline in prescription pain medication utilization over 3 years. Patients who continued taking pain medications experienced nominal dose reductions, and patients who received selumetinib continuously experienced a decrease in prescription pain medication utilization.

P1, N=19, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Mar 2026 --> Mar 2027

This Perspective synthesizes recent developments, including gene-based reclassification, emergence of MEK inhibitor therapy in NF1, renewed evaluation of bevacizumab and kinase-pathway inhibitor brigatinib, the discovery of a novel TβR1-RKIP pathogenic axis, and a brain-penetrant HDAC inhibitor in NF2-SWN. These insights highlight a shift toward precision-medicine strategies and mechanistically driven therapies poised to redefine future clinical care.

P1/2, N=217, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Jul 2026 --> Mar 2027 | Trial primary completion date: Jul 2026 --> Jan 2026

The safety profile of selumetinib was generally consistent with the findings of the phase 2 SPRINT trial and Japanese phase 1 trial. No new safety concerns were identified.