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A Phase II Study of Binimetinib in Children and Adults with NF1 Associated Plexiform Neurofibromas (PNOC010)


This is a phase II open label study that will evaluate children ≥ 1 year of age and adults with neurofibromatosis type 1 (NF1) and plexiform neurofibromas treated with the MEK inhibitor, binimetinib. The primary objective is to determine if there is an adequate level of disease responsiveness to binimetinib in children and adults with NF1 and inoperable plexiform neurofibromas. The objective response to binimetinib is defined as ≥ 20% decrease in tumor volume reduction by 12 courses.

As of Protocol version 3.0, study participants who completed 24 courses of binimetinib and discontinued treatment at that time per protocol, but subsequently have tumor progression (>20% increase in volume) within one year of therapy completion, will be allowed to restart binimetinib at the same dose they were receiving at the end of the initial 24 courses, on the Re-Treatment Arm of the study.


Binimetinib will be administered to adult subjects orally at a dose of 30 mg BID. Subjects who have been enrolled prior to protocol version 2.0 and tolerate binimetinib at 45 mg PO BID can continue on that dosing regimen if the treating physician believes that this is in the best interest of the patient.

Binimetinib will be administered to children between 1 and 17 years orally as a BID schedule at a dose of 32 mg/m2 (maximum: 45mg dose).


This study is open to all ages 1 year and older, all sexes, but does not accept healthy volunteers.


This phase II open label study will evaluate children ≥ 1 year of age and adults with neurofibromatosis type-1 (NF1) and plexiform neurofibromas treated with the MEK inhibitor binimetinib. The primary aim of the study will be to assess quantitative radiographic response in a target lesion. Initially, adult subjects (Stratum A) received binimetinib by mouth on a BID dosing schedule of 45mg/dose (the established adult RP2D). Because 4 of the first 11 enrolled subjects chose to remove themselves from study for “intolerable” skin adverse events (AE’s) at the 45 mg BID dosing, the starting dose for the adult stratum is reduced to 30 mg BID in Protocol Version 2.0. Pediatric subjects (Stratum B) will be treated on a BID dosing schedule of 32 mg/m2, which has been established as the pediatric RP2D by study NCT02285439; maximum dose will be 45mg/dose (which corresponds to the adult MTD). Given the difference in the clinical behavior of plexiform neurofibromas in the adult and pediatric setting, Stratum A and B will be analyzed independently. Each course is 4 weeks duration. Subjects who have a 20% or greater reduction in target tumor volume at the end of 12 courses can continue on therapy for up to an additional year (maximum of 24 total courses). However, subjects who do not achieve at least 20% reduction in volume of the target tumor after 12 courses will be considered treatment failures and taken off study.


  • Sabine Mueller, MD, Chair
  • Michael Fisher, MD, Co-Chair
  • Alyssa Reddy, MD, Co-Chair


Enrollment is closed. This study is active.