Phase 2 trial of veliparib, local irradiation, and temozolomide in patients with newly diagnosed high-grade glioma: a Children’s Oncology Group study

Karajannis MA, Onar-Thomas A, Lin T, Baxter PA, Boué DR, Cole BL, Fuller C, Haque S, Jabado N, Lucas JT Jr, MacDonald SM, Matsushima C, Patel N, Pierson CR, Souweidane MM, Thomas DL, Walsh MF, Zaky W, Leary SES, Gajjar A, Fouladi M, Cohen KJ. Phase 2 trial of veliparib, local irradiation, and temozolomide in patients with newly diagnosed high-grade glioma: a Children’s Oncology Group study. Neuro Oncol. 2025 May 15;27(4):1092-1101. doi: 10.1093/neuonc/noae247. PMID: 39560182; PMCID: PMC12083075.

The outcome for pediatric patients with high-grade glioma (HGG) remains poor. Veliparib, a potent oral poly(adenosine diphosphate-ribose) polymerase (PARP) 1/2 inhibitor, enhances the activity of radiotherapy and DNA-damaging chemotherapy. We conducted a single-arm, non-randomized phase 2 clinical trial to determine whether treatment with veliparib and radiotherapy, followed by veliparib and temozolomide, improves progression-free survival in pediatric patients with newly diagnosed HGG without H3 K27M or BRAF mutations, compared to patient-level data from historical cohorts with closely matching clinical and molecular features. Following surgical resection, newly diagnosed children with non-metastatic HGG were screened by rapid central pathology review and molecular testing. Eligible patients were enrolled on Stratum 1 (IDH wild-type) or Stratum 2 (IDH mutant).