Efficacy and safety of dordaviprone (ONC201) in prospective clinical trials of adult and pediatric recurrent H3 K27M-mutant diffuse glioma patients.

作者：Ashley Sumrall, Joshua E. Allen, Stephen Bagley, Thomas M. Brundage, Nicholas Butowski, Jessica Clymer, Aya Haggiagi, Carl Koschmann, Sylvia C. Kurz, Tobey J. MacDonald, Nazanin Majd, Sabine Mueller, Samuel Ramage, Rohinton S. Tarapore, Reena Thomas, Yoshie Umemura, Wafik Zaky, Yazmín Odia · 发表于：Journal of Clinical Oncology · 年份：2025 · DOI：10.1200/jco.2025.43.16_suppl.10017 · 被引用次数：5 · 研究领域：Glioma Diagnosis and Treatment、ATP Synthase and ATPases Research、Mitochondrial Function and Pathology

10017 Background: Dordaviprone (ONC201), a first in class imipridone, has demonstrated safety and efficacy in an integrated analysis of patients with recurrent H3 K27M-mutant diffuse midline glioma across clinical studies. Here, we report efficacy and safety findings from two prospectively defined clinical trial arms that evaluated single-agent dordaviprone response in recurrent H3 K27M-mutant glioma. Methods: Phase 2 trialONC013 (Arm B) and Phase 1 trial ONC014 (Arm F) were designed to evaluate the objective response rate (ORR) by RANO-HGG criteria of dordaviprone in adult and pediatric patients, respectively, with recurrent H3 K27M-mutant diffuse glioma. Open label dordaviprone was administered once weekly at 625 mg for adults and at a dose scaled by body weight for pediatrics. Responses were investigator-assessed by RANO criteria. Eligibility required measurable enhancing recurrence by RANO-HGG criteria, radiotherapy completed ≥90 days prior to dordaviprone unless unequivocal progression qualified per RANO, Karnofsky or Lansky performance status >60. DIPG, spinal tumors, leptomeningeal disease, and CSF dissemination were excluded. Results: ONC013 Arm B enrolled 30 patients (median age 32, range, 21-66 years) with the majority having a primary midline non-brainstem tumor (n = 19, 63.3%) and one prior recurrence (n = 22, 73.3%). The ORR was 16.7% (95% CI, 5.6-34.7) with 5 partial responses (PR). The median duration of response (DOR) and time to response (TTR) were 15.1 mo...