Abstract
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 marginal benefits. ONC201 (Dordaviprone), a brain penetrant dopamine receptor D2 antagonist has shown efficacy in recent clinical trials of DMG-P. Here we present our experience of DMG-P patients treated with ONC201. 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 with DMG-P; Thirteen (N=13/19) patients were diagnosed based on clinical / MRI findings; six patients had biopsy confirmed DMG-P. All patients were treated with RT. Six (n=6/19, 31%) patients were treated with ONC201 at first recurrence post-RT through the expanded access program. Four of the six (N=4/6, 66%) patients also received repeat RT at first recurrence. ONC201 was tolerated well without any dose modifying toxicities. Median progression free survival (PFS) and median overall survival (OS) from initial diagnosis in the ONC201 vs. non-ONC201 patients was 9.05 months (4.5-30.1) compared to 4.6 months (1.9-10.7), and 19.2 months (11.3-33.1) compared to 8.2 months (1.9-19.7), respectively. Two patients are still alive (at 12 and 33 months) on therapy. Conclusion: Our data suggest that ONC201 in combination with repeat RT has clinical efficacy in the treatment of recurrent DMG-P tumors in children. Ongoing clinical trials of combination therapies of ONC201 in DMG-P both in upfront and recurrent settings will validate our findings.