Real life data of ONC201 (dordaviprone) in pediatric and adult H3K27-altered recurrent diffuse midline glioma: Results of an international academia-driven compassionate use program.

Abstract

Introduction: H3K27-altered diffuse midline gliomas (DMG) have limited therapeutic options and a very poor prognosis. Encouraging responses were observed in early clinical trials with ONC201. As ONC201 was unavailable in Europe, a compassionate use program supported by the French Authorities was launched for patients at progression after standard of care radiotherapy.

Methods: This program was developed by the French Society of Pediatric Oncology (SFCE) and Association des Neuro-Oncologues d'Expression Française in collaboration with the French National Agency For Medicines and Health Products Safety and Parents Associations.

Results: 174 patients (102 children, 72 adults) from 14 countries were treated from November 2021 to August 2023 at Gustave Roussy Institut (Villejuif, France). 37 % received a second course of irradiation at the time of relapse. Median duration of treatment was 57 days or 1,9 months (mo) (range 1-456 days). Median OS since diagnosis for the whole cohort was 466 days or 15,5 mo (112-2612 days); 426 or 14,2 mo (112-2612 days) and 590 or 19,6 mo (range 160-1881) for children and adults, respectively (p = 0.001). Median OS after ONC201 start was 143 days or 4,7 mo (1-711 days) for the whole cohort. Univariate and multivariable analysis identified site (thalamus) and age (older) as favorable prognostic factors. Reirradiation was associated with significantly longer survival after ONC201 start only in children.

Conclusion: While the efficacy of ONC201 needs validation in a controlled randomized clinical trial, our real-life data support a better outcome for patients with thalamic tumors treated with ONC201. We demonstrated furthermore the feasibility of a successful academia-driven compassionate use program.