The following article features coverage from the Society for Neuro-Oncology 2021 meeting. Click here to read more of Cancer Therapy Advisor’s conference coverage.

Among patients with recurrent H3 K27M-mutated diffuse midline glioma, ONC201 monotherapy may yield a durable response, according to research presented at the Society for Neuro-Oncology (SNO) 2021 Annual Meeting.

H3 K27M-mutated diffuse midline glioma, which is most frequently diagnosed in younger patients, is generally considered incurable.

“There are currently no effective therapies after first-line radiation,” said Isabel Arrillaga-Romany, MD, PhD, of Massachusetts General Hospital in Boston, who presented this study at SNO 2021. H3 K27M is, furthermore, the most common histone mutation in glioma.

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ONC201, a first-in-class, orally administered DRD2/3 antagonist and ClpP agonist, has been shown in preclinical research to have an anticancer mechanism of action. For this study, researchers evaluated the safety and efficacy of ONC201 in pediatric and adult patients with H3 K27M-mutated diffuse midline glioma.

Overall, 50 patients were enrolled and treated with ONC201. The median patient age was 30 years (range, 8-70 years), 54% of patients were men, 78% were White, and 72% had a performance status of 80 or higher. Most (88%) patients had received prior temozolomide.

The median follow-up was 18.8 months. By Response Assessment in Neuro-Oncology High-Grade Glioma criteria, the overall response rate was 20%, with 1 complete response and 9 partial responses noted. The disease control rate was 40%, and the median duration of response was 11.2 months.

Among patients with a performance status of less than 80, 20.6% achieved a confirmed performance status improvement.

The progression-free survival rate was 35% at 6 months and 30% at 12 months. The overall survival rate was 57% at 12 months and 35% at 24 months. The median overall survival was 13.7 months.

Serious adverse events were noted in 50% of patients. One event, a pulmonary embolism, was deemed related to treatment.

“For an invariably lethal disease … the safety profile and durable responses of ONC201 are compelling,” Dr Arrillaga-Romany said. “We hope to confirm the clinical utility and benefit of ONC201.”

Disclosures: This research was supported by Chimerix. Dr Arrillaga-Romany disclosed affiliations with Astex Pharmaceuticals and FORMA therapeutics.

Read more of Cancer Therapy Advisor’s coverage of SNO 2021 by visiting the conference page.


Arrillaga-Romany I. Clinical efficacy of ONC201 in recurrent H3 K27M-mutant diffuse midline glioma patients. Presented at SNO 2021; November 18-21, 2021. Abstract LTBK-05.