General Information

Koselugo (selumetinib) is a kinase inhibitor.

Koselugo is specifically indicated for the treatment of pediatric patients 2 years of age and older with neurofibromatosis type 1 (NF1) who have symptomatic, inoperable plexiform neurofibromas.

Koselugo is supplied as a capsule for oral administration. The recommended dosage of Koselugo is 25 mg/m2 orally twice daily (approximately every 12 hours) until disease progression or unacceptable toxicity. Please see drug label for the recommended dose of Koselugo based on body surface area (BSA). Take Koselugo on an empty stomach. Do not consume food 2 hours before each dose or 1 hour after each dose. Swallow Koselugo capsules whole with water. Do not chew, dissolve or open capsule. Do not administer to patients who are unable to swallow a whole capsule. Do not take a missed dose of Koselugo unless it is more than 6 hours until the next scheduled dose. If vomiting occurs after administration, do not take an additional dose, but continue with the next scheduled dose.

Mechansim of Action

Kolseugo (selumetinib) is an inhibitor of mitogen-activated protein kinase kinases 1 and 2 (MEK1/2). MEK1/2 proteins are upstream regulators of the extracellular signal-related kinase (ERK) pathway. Both MEK and ERK are critical components of the RAS-regulated RAF-MEK-ERK pathway, which is often activated in different types of cancers.

Clinical Trial Results

The FDA approval of Koselugo was based on positive results from the National Cancer Institute (NCI) Cancer Therapy Evaluation Program (CTEP)-sponsored Phase II SPRINT Stratum 1 trial coordinated by the NCI’s Center for Cancer Research, Pediatric Oncology Branch. The an open-label, multicenter, single arm trial enrolled patients with NF1 with inoperable plexiform neurofibroma (PN), defined as a PN that could not be completely removed without risk for substantial morbidity due to encasement of, or close proximity to, vital structures, invasiveness, or high vascularity of the PN. Patients were also required to have significant morbidity related to the target PN. A total of 50 pediatric patients received Koselugo. The median age was 10.2 years. Patients received Koselugo 25 mg/m2 orally twice daily until disease progression or unacceptable toxicity. Results showed an overall response rate (ORR) of 66% (33 of 50 patients, confirmed partial response). ORR is defined as the percentage of patients with confirmed complete or partial response of at least 20% reduction in tumor volume.