ONC201 in Pediatric H3 K27M Gliomas

This is a multicenter, open-label, seven arm, dose escalation, phase I study of oral
ONC201 in pediatric patients with newly diagnosed Diffuse Intrinsic Pontine Glioma (DIPG)
and recurrent/refractory H3 K27M gliomas. Arm A will define the RP2D for single agent
ONC201 in pediatric patients with glioma who are positive for the H3 K27M mutation
(positive testing in CLIA laboratory) and have completed at least one line of prior
therapy. This will allow for recurrent patients and also patients who have not yet
recurred, but have completed radiation and will inevitably recur based on prior clinical
experience and the literature. Arm B will define the RP2D for ONC201 in combination with
radiation in pediatric patients with newly diagnosed DIPG. Arm C will determine
intratumoral drug concentrations and biomarker expression in pediatric patients with
midline gliomas. Arm D will determine H3 K27M DNA levels and drug concentrations in the
CSF of pediatric H3 K27M-mutant glioma patients. Arm E will determine the RP2D for single
agent ONC201 administered as a liquid formulation in Ora-Sweet to patients with DIPG
and/or H3 K27M glioma. Arm F is a dose expansion cohort to confirm the safety and
estimate the efficacy in recurrent H3 K27M-mutant glioma population at the RP2D. Arm G
will define the RP2D for single agent ONC201 given on two consecutive days of each week
in pediatric patients with glioma who are positive for the H3 K27M mutation and have
completed at least one line of prior therapy.

Treatment Sites in Georgia