Newly Approved Agent for Diffuse Midline Glioma Shows Tolerable AE Profile

Contextualized by the approval of dordaviprone (Modeyso), patients with diffuse midline glioma harboring H3 H27M mutations, Ashley L. Sumrall, MD, in a conversation with CancerNetwork®, discussed notable toxicities that may arise when treating patients with dordaviprone.¹

Sumrall, a neuro-oncologist at Atrium Health Levine Cancer Institute and investigator in 2 clinical trials evaluating dordaviprone in recurrent H3 K27M-mutant diffuse midline glioma (NCT03295396; NCT03416530), expressed that patient education regarding receipt of the agent is straightforward, given its oral administration once weekly.² She additionally explained that many adverse effects (AEs) are rare and low severity.

To illustrate this, she remarked that patients may often report fatigue and headaches, but these symptoms are often associated with the underlying condition. Notable AEs include nausea and vomiting for pediatric patients, as well as decreases in lymphocyte counts, which she said her team monitors for.

Prescribing information for dordaviprone includes warnings and precautions for hypersensitivity, QTc interval prolongation, and embryo-fetal toxicity. Additionally, dordaviprone was recommended at a dose of 625 mg orally once weekly for adults, and the recommended dosage is based on body weight for pediatric patients.

Transcript:

One of the nice things about dordaviprone is that it is an oral agent, and it is given once weekly. [Education] for patients and families is straightforward. Then, if you look at the available data, many of the [adverse] effects that are profiled are rare, so they do not happen to many of the patients, but also the severity is also low.

For example, patients may report fatigue, but it is common for patients with brain tumors to report fatigue. We do mention that headaches can happen, but that is also something that is common for patients with this condition. We did find in the pediatric population that there were some individuals who had a little more nausea and vomiting, so we monitor for that. Then we found that the lymphocyte count was decreased in some [patients], and we recommend routine blood monitoring.

References

1. FDA grants accelerated approval to dordaviprone for diffuse midline glioma. News release. FDA. August 6, 2025. Accessed August 12, 2025. https://tinyurl.com/5hdypp4h
2. Sumrall A, Allen J, Bagley S, et al. Efficacy and safety of dordaviprone (ONC201) in prospective clinical trials of adult and pediatric recurrent H3 K27M-mutant diffuse glioma patients. J Clin Oncol. 2025;43(suppl 16):10017. doi:10.1200/JCO.2025.43.16_suppl.10017