SJ901: Evaluation of Mirdametinib in Children, Adolescents, and Young Adults With Low-Grade Glioma

The objectives of this study are:

Phase 1

Primary Objectives:

* To determine the safety and tolerability and estimate the maximum tolerated dose (MTD)/recommended phase 2 dose (RP2D) of mirdametinib dosed twice daily on a continuous schedule in pediatric patients with progressive or recurrent low-grade glioma. * To characterize the plasma pharmacokinetics (PK) of mirdametinib.

Phase 2

Cohort 1: Newly diagnosed and/or previously untreated (except surgery)

Primary Objectives:

* To assess the efficacy, defined as the sustained objective response rate \[a Partial Response (PR), Major Response, and/or Complete Response (CR) sustained over 8 weeks\] observed over any time on active treatment with mirdametinib in previously untreated patients (except surgery) with WHO grade I or grade II glioma. * To characterize the plasma pharmacokinetics of mirdametinib in children, adolescents, and young adults with low-grade gliomas. * To describe the toxicity profile of mirdametinib in pediatric patients.

Secondary Objectives:

* Estimate the efficacy of mirdametinib as measured by progressive free survival (PFS) and overall survival (OS) in patients with previously untreated WHO grade I or grade II glioma. * To describe treatment responses (Progressive Disease, Stable Disease, Minor Response, Partial Response, Major Response, and Complete Response) observed in previously untreated patients (except surgery) with WHO grade I or grade II glioma over any time on active treatment with mirdametinib. * To characterize and monitor patient neurocognitive function and quality of life in patients while on study.

Cohort 2: Recurrent and/or Progressive without prior exposure to MEK inhibitors

Primary Objectives:

* To assess the efficacy, defined as the sustained objective response rate (a PR, Major Response, and/or CR sustained over 8 weeks) observed anytime on active treatment with mirdametinib in patients with recurrent and/or progressive WHO grade I or grade II glioma not previously treated with MEK inhibitors. * To characterize the plasma pharmacokinetics of mirdametinib in children, adolescents, and young adults with low-grade gliomas. * To describe the toxicity profile of mirdametinib in pediatric patients with recurrent or progressive disease, not previously treated with MEK inhibitors.