Experimental Drug Shows Early Promise for Rare, Incurable Brain Tumors

A study of five early-stage clinical trials has found that an experimental drug may have favorable results for a rare and incurable type of brain tumor, for which there are very few treatment options.

The research is published in the Journal of Clinical Oncology.

Finding a drug for an intractable cancer

Diffuse midline gliomas (DMGs) are a rare type of brain tumor that primarily affects children, representing 10–15% of all childhood brain tumors.

Some of these gliomas are linked to a gene mutation called H3 K27M, which results in particularly aggressive tumors and a poor survival rate; the median overall survival is just one year from diagnosis.

Treatment is limited as the location of the tumors in the brain often makes surgery difficult, leaving radiation as the only effective option. However, even with radiation, almost all patients eventually relapse ­– making targeted treatments for these tumors an area of unmet need.

Preclinical studies using the experimental drug ONC201 (dordaviprone) have shown some anti-tumor effects in animal models, including H3 K27M-mutant gliomas. Clinical trials in humans have also taken place.

In the current study, researchers from Northwestern University analyzed data from five previous studies that investigated the effects of ONC201 in DMG patients.

“A major step forward”

The 5 studies assessed included a total of 46 adults and 4 children with recurrent H3 K27M-mutant DMG who received the drug as an oral monotherapy, i.e., using it alone as a single drug.

Of the participants, 30% had a favorable overall response rate to the drug and 20% had an objective response, according to the Response Assessment in Neuro-Oncology high-grade glioma criteria.

Patients also reported side effects of the treatment, the most common of which was fatigue (10% of patients). The drug was generally well-tolerated, with no patients discontinuing treatment.

"Dordaviprone was shown to be effective in these recurrent histone-mutated gliomas, for which we had no other real management options," said Dr. Karan Dixit, assistant professor of neuro-oncology at Northwestern University Feinberg School of Medicine.

"Even in situations where the patient has received prior treatment, the cancers tend to come back more aggressive and less responsive to treatment,” Dixit explained. “So, to have a treatment that was not only well tolerated, but had a meaningful response in about 20% to 30% of patients, is a major step forward. That may not seem like a lot, but these are patients that we had nothing for before."

Overall, the findings conclude that ONC201 monotherapy was well-tolerated by these patients and brought about durable and clinically meaningful effects on their tumors.

The researchers are now preparing a trial to investigate the drug’s efficacy in patients with newly diagnosed DMG: “We’ll be the only site in Illinois to be enrolling people in the trial for this drug,” Dixit said.

Reference: Arrillaga-Romany I, Gardner SL, Odia Y, et al. ONC201 (Dordaviprone) in recurrent H3 K27M–mutant diffuse midline glioma. JCO. 2024:JCO.23.01134. doi: 10.1200/JCO.23.01134

This article is a rework of a press release issued by Northwestern University. Material has been edited for length and content.