According to results from a phase 1/2 study, dordaviprone, a first-in-class imipridone, demonstrated clinical promise and safety among patients with recurrent H3 K27M-mutated diffuse glioma. 

These data were first presented by Ashley Sumrall, MD, Levine Cancer Institute, Charlotte, North Carolina, at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago, Illinois.

Researchers enrolled adult (phase 2 ONC013; n = 30) and pediatric (phase 1 ONC014; n = 11) patients to receive once weekly dordaviprone either at 625 mg (adult cohort) or scaled by body weight (pediatric cohort). Patients were required to have undergone radiotherapy ≥ 90 days prior to trial enrollment. Patients with diffuse intrinsic pontine glioma, spinal tumors, leptomeningeal disease, and cerebrospinal fluid dissemination were excluded from trial enrollment. The primary end point was objective response rate (ORR). Key secondary end points included median duration of response, median time to response, progression-free survival (PFS), overall survival (OS), and safety. 

In the adult cohort, the ORR was 16.7%. The median duration of response was 15.1 months and the median time to response was 3.8 months. Grade ≥3 treatment-related adverse events occurred in 3 patients. No treatment-related serious adverse events were reported and 1 treatment-related adverse event led to dose reduction. In the pediatric cohort, the ORR was 9.1% with 2 radiographic responses and 1 partial response reported. The median duration of response was 8.5 months and time to response was 4.3 months. The 12-month PFS rate was not reached, and the 12-month OS rate was 27.3%. Grade ≥3 treatment-related adverse events occurred in 1 patient. No treatment-related serious adverse events, treatment-related deaths, or treatment-related adverse events that led to treatment discontinuation were reported. 

“In prospective clinical trials designed to evaluate ORR, single-agent dordaviprone response and safety in adult and pediatric recurrent H3 K27M-mutant diffuse glioma were similar to previously pooled analyses,” concluded Dr Sumrall et al. 

Source: 

Sumrall A, Allen J, Bagley S, et al. Efficacy and safety of dordaviprone (ONC201) in prospective clinical trials of adult and pediatric recurrent H3 K27M-mutant diffuse glioma patients. Presented at 2025 ASCO Annual Meeting. May 30-June 3, 2025; Chicago, IL. Abstract 10017