Pooled analysis of five studies of ONC201 (dordaviprone) for recurrent H3 K27M-mutant diffuse midline glioma

Histone 3 (H3) K27M-mutant diffuse midline glioma (DMG) has a dismal prognosis with no established effective therapy beyond radiation. A pooled analysis of five studies evaluated single-agent oral ONC201 (dordaviprone), a first-in-class imipridone, for recurrent H3 K27M-mutant DMG. The analysis included 50 patients (4 pediatric, 46 adult) with measurable disease by RANO high-grade glioma criteria and performance score ≥ 60 who were ≥ 90 days from radiation; pontine and spinal tumors were ineligible. The overall response rate (RANO-HGG; primary end point) was 20% (95% CI 10,0-33,7) with median time to response 8.3 months (range 1.9-15.9) and median duration of response 11.2 months (95% CI 3.8-NR). A ≥ 50% corticosteroid dose reduction occurred in 7 of 15 evaluable patients (46.7%; 95% CI 21.3-73.4); performance score improvement occurred in 6 of 34 evaluable patients (20.6%; 8.7-37.9). Grade 3 treatment-related treatment-emergent adverse events occurred in 20% of patients; there were no grade 4 or 5 TR-TEAEs or discontinuations. The authors conclude that ONC201 monotherapy was well tolerated and exhibited durable and clinically meaningful efficacy in recurrent H3 K27M-mutant DMG.