! I’m your host today, Caroline Seymour.

, which provides oncology professionals with the resources and information they need to provide the best patient care. In both digital and print formats, 

 covers every angle of oncology practice, from new technology to treatment advances to important regulatory decisions.

In today’s episode, sponsored by Chimerix, we had the pleasure of speaking with Stephen Bagley, MD, MSCE, an assistant professor of medicine in hematology-oncology at the Hospital of the University of Pennsylvania, as well as section chief in Neuro-Oncology and an assistant professor of medicine in neurosurgery at Penn Medicine in Philadelphia.

In our exclusive interview, Dr Bagley discussed the evaluation of the small molecule ONC201 in the phase 3 ACTION trial (NCT05580562) in patients with 

mutant diffuse midline gliomas and explained why clinicians should consider the trial for their patients.

That’s all we have for today! Thank you for listening to this episode of 

, sponsored by Chimerix. Check back on Mondays and Thursdays for exclusive interviews with leading experts in the oncology field.

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Podcasts

Dr Bagley discusses the evaluation of the small molecule ONC201 in the phase 3 ACTION trial in H3 K27M–mutant diffuse midline gliomas.

Bagley Summarizes the ACTION trial of ONC201 in H3 K27M–Mutant Diffuse Midline Gliomas 

Dr Bagley on the ACTION Trial of ONC201 in H3K27M-Mutant Diffuse Midline Gliomas

Stephen Bagley, MD, MSCE, assistant professor of medicine, hematology-oncology, University of Pennsylvania Hospital, assistant professor of medicine, neurosurgery, Penn Medicine, discusses the evaluation of the small molecule ONC201 in the phase 3 ACTION trial (NCT05580562) for patients with 

Diffuse midline gliomas are rare malignancies, with a higher incidence in pediatric populations, Bagley begins. This tumor type has historically been considered difficult to treat due to its location in the central nervous system, spanning from the spinal cord to the brain stem to the thalamus, Bagley explains.

The first-in-class imipridone ONC201 (dordaviprone) penetrates the blood-brain barrier to target the dopamine receptor D2/3 (DRD2) which in turn activates an integrated stress response, thereby triggering programmed cell death in cancer cells. DRD2 is hypothesized to be enriched in these brain structures, indicating that ONC201 may have a role in the treatment armamentarium as an effective antagonist. An integrated pooled analysis of 5 open-label, early-phase trials of ONC201 has demonstrated promising efficacy signals with the agent in patients with recurrent diffuse midline glioma. Orally administered ONC201 also exhibited radiographic responses in a subset of patients with recurrent disease, Bagley notes.

Based on these initial data, the large, international, randomized ACTION trial was initiated, Bagley says. The study will enroll patients with newly diagnosed 

-mutant diffuse glioma who completed standard frontline radiotherapy. Patients will be randomly assigned 1:1:1 to receive either placebo, once-weekly ONC201, or twice-weekly ONC201 on 2 consecutive days.

The study’s primary efficacy end points are overall survival (OS) and progression-free survival (PFS), evaluated with response assessment in neuro-oncology-high grade glioma criteria by blinded independent central review. Other secondary objectives include safety, additional efficacy end points, clinical benefit, quality of life, pharmacokinetics, biomarkers, and healthcare resource utilization.

The ongoing trial will assess the efficacy of ONC201 in a broader context and provide insight into its potential role in diffuse midline glioma, Bagley explains. As recruitment progresses, the oncology community anticipates that the results of this study will further inform the management of this challenging tumor, he says. The ACTION study is currently enrolling in the United States, with plans to open at other international sites.

Videos

Stephen Bagley, MD, MSCE, discusses the phase 3 ACTION trial evaluating ONC201 in H3K27M-mutant diffuse midline gliomas.

Stephen Bagley, MD, MSCE

Articles

Bagley Summarizes the ACTION trial of ONC201 in H3 K27M–Mutant Diffuse Midline Gliomas

Dr Bagley on the ACTION Trial of ONC201 in H3K27M-Mutant Diffuse Midline Gliomas