1. Pediatric and adult H3 K27M-mutant diffuse midline glioma treated with the selective DRD2 antagonist ONC201
- Author
-
Isabel Arillaga-Romany, Yoshie Umemura, Ziad Khatib, Krystal Merdinger, Rohinton Tarapore, Andrew S. Chi, Sabine Mueller, Martin Stogniew, Matthias A. Karajannis, Angela J. Waanders, David N. Korones, Cassie Kline, Yazmin Odia, Joshua E. Allen, Matthew Hall, Wafik Zaky, Irene Cherrick, Jane E. Minturn, Minesh P. Mehta, Shiao Pei Weathers, Toba N. Niazi, Sharon Gardner, Wolfgang Oster, Soumen Khatua, Doured Daghistani, Lee Schalop, Nicole Shonka, Xiao-Tang Kong, Ashley Sumrall, Tracy T. Batchelor, and Patrick Y. Wen
- Subjects
Adult ,Male ,Cancer Research ,medicine.medical_specialty ,Neurology ,Adolescent ,Pyridines ,Radiography ,Antineoplastic Agents ,Disease ,Malignancy ,Heterocyclic Compounds, 4 or More Rings ,Article ,Histones ,Young Adult ,03 medical and health sciences ,0302 clinical medicine ,Median follow-up ,Glioma ,Internal medicine ,Humans ,Medicine ,Young adult ,Child ,Brain Neoplasms ,Receptors, Dopamine D2 ,business.industry ,Imidazoles ,Prognosis ,medicine.disease ,Survival Rate ,Pyrimidines ,Oncology ,Child, Preschool ,030220 oncology & carcinogenesis ,Expanded access ,Mutation ,Female ,Neurology (clinical) ,business ,030217 neurology & neurosurgery ,Follow-Up Studies - Abstract
BACKGROUND: H3 K27M-mutant diffuse midline glioma is a fatal malignancy with no proven medical therapies. The entity predominantly occurs in children and young adults. ONC201 is a small molecule selective antagonist of dopamine receptor D2/3 (DRD2/3) with an exceptional safety profile. Following up on a durable response in the first H3 K27M-mutant diffuse midline glioma patient who received ONC201 (NCT02525692), an expanded access program was initiated. METHODS: Patients with H3 K27M-mutant gliomas who received at least prior radiation were eligible. Patients with leptomeningeal spread were excluded. All patients received open-label ONC201 orally once every week. Safety, radiographic assessments, and overall survival were regularly assessed at least every 8 weeks by investigators. As of August 2018, a total of 18 patients with H3 K27M-mutant diffuse midline glioma or DIPG were enrolled to single patient expanded access ONC201 protocols. Among the 18 patients: seven adult (>20 years old) and seven pediatric (
- Published
- 2019
- Full Text
- View/download PDF