Modeyso received FDA accelerated approval based on an overall response rate (ORR) of 22% in a highly aggressive, ultra-rare brain tumor with historically limited treatment options. How do you interpret this milestone in the context of current standards of care for H3 K27M-mutant DMG?

Among responders in the integrated analysis, the median duration of response was 10.3 months, with 73% maintaining responses for at least six months. Given the median survival for recurrent DMG is typically under six months, how clinically meaningful are these findings for patients and families?

H3 K27M-mutant DMG primarily affects children and young adults, yet the Modeyso trials included both populations. Were there notable differences in response rates, tolerability, or safety signals between pediatric and adult patients?

Modeyso was associated with serious adverse events in 33% of patients, including hydrocephalus, seizures, and QTc prolongation. How do you approach weighing these risks against the potential clinical benefit, particularly in such a high-mortality disease?

Dordaviprone targets mitochondrial ClpP activation and DRD2 inhibition, ultimately restoring histone H3 K27 trimethylation. How significant is this dual mechanism in reshaping treatment strategies for epigenetically driven tumors, and could Modeyso be combined with radiotherapy or other targeted agents to enhance efficacy?

The ongoing Phase 3 ACTION study is designed to verify Modeyso’s clinical benefit in newly diagnosed patients following radiotherapy. What key endpoints and outcomes should the community focus on, and how might these results impact full FDA approval?

Before Modeyso, there were no FDA-approved systemic treatments for recurrent H3 K27M-mutant DMG. How do you see this approval influencing clinical trial design, research priorities, and patient advocacy within pediatric and adult neuro-oncology?

Despite this approval, outcomes remain challenging, and many patients will still experience rapid disease progression. What are the remaining gaps in care, and where do you anticipate the next wave of innovation for diffuse midline glioma treatment to come from?