KEY TAKEAWAYS
- The study aimed to evaluate the activity of ONC201 in non-midline H3K27M-mutant diffuse gliomas.
- The primary endpoint was ORR.
- The results demonstrated the ONC201 efficacy in H3K27M-mutant gliomas regardless of their location within the CNS, including nonmidline cerebrum.
Diffuse midline glioma, H3 K27-altered (H3 K27M-altered DMG), a type of brain cancer, is typically fatal, particularly affecting the young, with limited treatment options apart from radiotherapy. While the 2016 WHO CNS Tumors Classification identified H3K27M mutations as indicative, diagnosis was initially confined to midline gliomas.
Dordaviprone (ONC201), an oral investigational small molecule acting as a DRD2 antagonist and ClpP agonist, has shown promising outcomes in treating recurrent H3K27M-mutant DMG.
Yazmin Odia and her team spearheaded the study that aimed to assess the efficacy of ONC201 in non-midline H3K27M-mutant diffuse gliomas.
The study enrolled patients with recurrent non-midline H3K27M-mutant diffuse gliomas who received treatment with ONC201 across five trials. Eligibility criteria included measurable disease according to the Response Assessment in Neuro-Oncology (RANO) high-grade glioma (HGG) criteria, Karnofsky/Lansky performance score (KPS/LPS) ≥60, and a minimum of 90 days from radiation. The primary endpoint was the overall response rate (ORR).
About 5 patients with cerebral gliomas (3 frontal, 1 temporal, and 1 parietal) met inclusion criteria. Investigators reported one complete and one partial response. Blinded independent central review confirmed an ORR by RANO criteria for two patients; however, one patient was deemed nonmeasurable, and another was classified as stable. Additionally, a responding patient experienced improved mobility and alertness.
The study reported the efficacy of ONC201 extends to H3K27M-mutant gliomas regardless of their location within the CNS.
Source: https://academic.oup.com/neuro-oncology/advance-article/doi/10.1093/neuonc/noae021/7612669
Odia Y, Hall MD, Cloughesy TF, et al. (2024) ‘’Selective DRD2 Antagonist and ClpP Agonist ONC201 in a Recurrent Non-midline H3 K27M-mutant Glioma Cohort.’’ Neuro-Oncology, 2024;, noae021, https://doi.org/10.1093/neuonc/noae021.
