# ACTION

Source: https://onco.cc/trials/action-dmg/  
OnCo record `action-dmg` (Trial). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

ACTION is the first placebo-controlled phase 3 trial ever run in diffuse midline glioma, the childhood brain-stem tumour that radiotherapy alone has never cured. It asks whether taking dordaviprone after radiotherapy lengthens life.

## Summary

Randomised, double-blind, placebo-controlled phase 3 in patients aged 2 years and older with newly diagnosed H3 K27M-mutant diffuse glioma who have completed front-line radiotherapy; participants are randomised to dordaviprone once weekly, dordaviprone on two consecutive days weekly, or placebo. Primary endpoints are overall survival and progression-free survival. Dordaviprone (ONC201) is an imipridone that antagonises DRD2 and activates the mitochondrial protease ClpP, with activity concentrated in H3 K27M-mutant tumours in earlier single-arm studies; the FDA granted accelerated approval in August 2025 for recurrent H3 K27M-mutant diffuse midline glioma on the basis of pooled single-arm response data, with ACTION as the confirmatory trial. Jazz Pharmaceuticals acquired Chimerix in 2025 and now sponsors the study. Recruiting across North America, Europe, Asia and Australia; estimated enrolment 510.

## Fields

- Kind: Trial
- Status: recruiting
- Last checked: 2026-09-10
- Tags: nci-coverage; paediatric; cns
- Registry id: NCT05580562
- Phase: 3
- Setting: Newly diagnosed H3 K27M-mutant diffuse glioma after completion of radiotherapy: dordaviprone (ONC201) vs placebo, two dosing schedules
- Sponsor: Jazz Pharmaceuticals (Chimerix until 2025)
- Enrolled: 510
- Replication: Single-arm phase 2 data only so far; ACTION is the confirmatory trial. Its result will also be the first randomised test of any systemic agent added to radiotherapy in this disease.

## Sources

- ClinicalTrials.gov NCT05580562: https://clinicaltrials.gov/study/NCT05580562
- Jazz Pharmaceuticals: dordaviprone: https://www.jazzpharma.com

## Connected records

- cancers: [Diffuse midline glioma, H3 K27-altered (including DIPG)](https://onco.cc/cancers/dipg-dmg/)
- drugs: [Dordaviprone](https://onco.cc/drugs/dordaviprone/)
- companies: [Jazz Pharmaceuticals](https://onco.cc/companies/jazz/)
- terms: [H3 K27M (diffuse midline glioma)](https://onco.cc/terms/h3k27m/), [RACE for Children Act](https://onco.cc/terms/race-for-children-act/)
- bottlenecks: [Rare and paediatric cancers without markets](https://onco.cc/bottlenecks/b-rare-cancers/), [The brain: barrier and sanctuary](https://onco.cc/bottlenecks/b-brain-delivery/)
- roadmaps: [Paediatric oncology roadmap: cooperative-group cures → engineered immunity → drugs developed for children first](https://onco.cc/roadmaps/paediatric-oncology-roadmap/)

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JSON: https://onco.cc/api/v1/entities/action-dmg.json