CTP-16. ONC201 (Dordaviprone) in the treatment of Diffuse Midline Glioma of the Pons in children: single center experience from Canada

Abstract INTRODUCTION Diffuse midline glioma of the pons (DMG-P) is a uniformly fatal brain tumor in children. Radiation therapy (RT) is the current standard of care with only transient benefits. Therapy at progression is very limited and offers minimal survival advantage. ONC201 (Dordaviprone), a brain penetrant dopamine receptor D2 antagonist has shown efficacy in recent clinical trials of DMG-P. We present our experience of DMG-P patients treated with ONC201 from a tertiary care center in Canada. METHODS We analyzed clinical data of patients diagnosed with DMG-P from 2012-2024 and compared outcomes of patients treated with and without ONC201. RESULTS There were nineteen patients diagnosed with DMG-P in the study period; Thirteen (N=13/19) patients were diagnosed based on clinical / MRI findings; six patients had biopsy confirmed DMG-P and all six patients had H3.3-K27M mutation. All but one patient were treated with RT. Six (n=6/19, 31%) patients were treated with ONC201 through the expanded access program from Chimerix: Two patients started ONC201 post-RT, prior to recurrence and four patients after first recurrence post-RT. Four of the six (N=4/6, 66%) patients also received repeat RT (RT2) at first recurrence. ONC201 was tolerated well without any dose modifying toxicities. Median progression free survival (PFS) from RT1 and median overall survival (OS) from initial diagnosis in the ONC201 vs non-ONC201 patients was 9.05 months (9.05 vs 4.6 mths, p=0.001) and 19.2 months (19.2 vs 8.2 mths, p=0.002) respectively. Patients treated with ONC201 experienced longer survival when compared to the non-ONC201 treated group (HR = 0.012, 95% CI: 0.000, 0.282; p = 0.005). Two patients on ONC201 are still alive (at 14 and 36 months) on therapy. CONCLUSION Our data suggest that ONC201 as monotherapy (Post-RT, prior to recurrence) or in combination with repeat RT(RT2) in the recurrent setting has clinical efficacy in the treatment of DMG-P tumors in children.