Dordaviprone Exhibits Durability in H3K27M-Mutated Diffuse Midline Glioma

In an interview with CancerNetwork®, Ashley L. Sumrall, MD, neuro-oncologist at Atrium Health Levine Cancer Institute and investigator in 2 clinical trials evaluating dordaviprone in recurrent H3K27M-mutated diffuse midline glioma (NCT03295396; NCT03416530), discussed efficacy findings that support the use of the agent in this patient population.1 This was contextualized by the FDA approval of the agent in this patient population on August 6, 2025.2

Sumrall began by highlighting her experience in using dordaviprone across patients with progressive and newly diagnosed gliomas, in both adult and pediatric patients, and stated that the drug was well tolerated in both age groups.

Regarding data, she outlined response durability among responders to treatment, explaining that patients may experience stable disease or partial responses for months. Additionally, Sumrall expressed that a longer follow-up will better elucidate the duration of response based on tumor location and patient age.

According to data from an integrated efficacy population across 5 trials that supported the FDA decision, dordaviprone exhibited an objective response rate of 22% (95% CI, 12%-36%) and median duration of response of 10.3 months (95% CI, 7.3-15.2). Of responders, the 6- and 12-month response rates were 73% and 27%, respectively.

Transcript:

We have been fortunate to work with this compound, using it for patients who have had progressive glioma. We have also had a study open for patients with newly diagnosed disease, and we have worked with adults [as well as] children and adolescents. If you look at the data that we have collected over the years, we have noticed a few things. First, the drug is well tolerated in children and adults.

Also, we have data from the adult study that individuals experienced stable disease or partial responses to therapy. When they experience these responses, they tend to be durable; they last for months. The duration of the [response] varies depending on the location of the tumor [as well as] the age of the patient, but we continue to follow individuals who are in the studies, and we are hopeful that we will get even better data.

References

1. 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
2. FDA grants accelerated approval to dordaviprone for diffuse midline glioma. FDA. August 6, 2025. Accessed August 12, 2025. https://tinyurl.com/5hdypp4h