This is a Phase II open-label study to investigate the safety and efficacy of ACT001 in patients with DIPG and H3K27-altered HGG.

Patients will be enrolled on either Cohort A for newly diagnosed DIPG or on Cohort B for those with progressive / refractory DIPG or progressive / recurrent / refractory H3K27-altered HGG.

Each cohort will receive ACT001 at 875 mg/m2 orally BID for 28 days (1 cycle of treatment), up to a maximum dose of 1700mg BID. If patients are experiencing clinical benefit from study therapy, they will continue to receive ACT001 in repeat 28-day cycles for up to 26 cycles (approximately 2 years) or until disease progression, whichever occurs first.

Continuation of treatment beyond 26 cycles may be considered if patients are receiving clinical benefit from the study, at the discretion of the sponsor and treating physician. Up to 60 patients total are expected to enrol.

The primary objective for Cohort A is to assess the overall survival for newly-diagnosed patients with DIPG treated with RT followed by ACT001.
The primary objective for Cohort B is to assess the rate of objective response rate in patients who have been treated with at least frontline focal RT and have progressive DIPG or progressive/recurrent/refractory H3K27-altered HGG who are treated with ACT001.