{"entity":{"id":"action-dmg","kind":"trial","name":"ACTION","aka":[],"tldr":"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.","status":"recruiting","asOf":"2026-09-10","links":[{"label":"ClinicalTrials.gov NCT05580562","url":"https://clinicaltrials.gov/study/NCT05580562"},{"label":"Jazz Pharmaceuticals: dordaviprone","url":"https://www.jazzpharma.com"}],"tags":["nci-coverage","paediatric","cns"],"related":[],"cancers":["dipg-dmg"],"sections":[],"technologies":[],"targets":[],"drugs":["dordaviprone"],"companies":["jazz"],"institutions":[],"pathways":[],"terms":["h3k27m","race-for-children-act"],"trials":[],"people":[],"bottlenecks":["b-brain-delivery","b-rare-cancers"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"nct":"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)","started":"2023-01-23","startedType":"actual","enrolled":510,"enrolledBasis":"registry","outcomes":[],"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."},"route":"/trials/action-dmg/","neighbours":{"cancer":[{"id":"dipg-dmg","kind":"cancer","name":"Diffuse midline glioma, H3 K27-altered (including DIPG)","route":"/cancers/dipg-dmg/"}],"drug":[{"id":"dordaviprone","kind":"drug","name":"Dordaviprone","route":"/drugs/dordaviprone/"}],"company":[{"id":"jazz","kind":"company","name":"Jazz Pharmaceuticals","route":"/companies/jazz/"}],"term":[{"id":"h3k27m","kind":"term","name":"H3 K27M (diffuse midline glioma)","route":"/terms/h3k27m/"},{"id":"race-for-children-act","kind":"term","name":"RACE for Children Act","route":"/terms/race-for-children-act/"}],"bottleneck":[{"id":"b-rare-cancers","kind":"bottleneck","name":"Rare and paediatric cancers without markets","route":"/bottlenecks/b-rare-cancers/"},{"id":"b-brain-delivery","kind":"bottleneck","name":"The brain: barrier and sanctuary","route":"/bottlenecks/b-brain-delivery/"}],"roadmap":[{"id":"paediatric-oncology-roadmap","kind":"roadmap","name":"Paediatric oncology roadmap: cooperative-group cures → engineered immunity → drugs developed for children first","route":"/roadmaps/paediatric-oncology-roadmap/"}]}}