ONC201-108 (ACTION-Studie)

This is a randomized, double-blind, placebo-controlled, parallel-group, international, Phase 3 study in patients with newly diagnosed H3 K27M-mutant diffuse glioma to assess whether treatment with ONC201 following frontline radiotherapy will extend overall survival and progression-free survival in this population. Eligible participants will have histologically diagnosed H3 K27M-mutant diffuse glioma and have completed standard frontline radiotherapy.

Participants will be randomized at baseline in a 1:1:1 ratio into parallel groups to receive ONC201 at one of two dose levels or placebo. Stratification factors include risk factors (higher, lower) and age (< 21 years, ≥ 21 years). The higher risk category includes enhancing tumors ≥ 10 cm2 in size, multifocal lesions (defined as more than one enhancing or non-enhancing tumor with intervening areas of normal brain signal), and/or a tumor located in the brainstem based on central magnetic resonance imaging (MRI) reading prior to radiotherapy. 

ONC201 is an orally active dopamine receptor D2 (DRD2) antagonist and caseinolytic protease proteolytic subunit (ClpP) agonist inducing apoptosis (cell death) in tumor cells and being developed as a treatment for central nervous system tumors harboring H3 K27M mutations. Previous open-label studies have shown efficacy in participants with recurrent disease. This is the first randomized, controlled study to evaluate the efficacy and safety of ONC201 in participants with H3 K27M-mutant diffuse glioma after completion of frontline radiotherapy.
ONC201 can be taken orally in capsule form or as a suspension.