I. To determine whether veliparib (ABT-888), when added to radiotherapy (RT) and
temozolomide, is efficacious for the treatment of patients with newly-diagnosed high-grade
glioma (HGG) whose tumors' molecular profile are wild-type for H3 K27M, BRAFV600E, and
II. To determine whether veliparib (ABT-888), when added to RT and temozolomide, is
efficacious for the treatment of patients with newly-diagnosed HGG whose tumors' molecular
profile are wild-type for H3 K27M and BRAFV600E and harbor an IDH1/2 mutation.
I. To explore associations of genomic, transcriptomic, and/or epigenetic alterations of the
tumors with treatment response and outcome.
II. To explore the extent to which patients with BRCA1/2 gene alterations and other
deoxyribonucleic acid (DNA) damaged genes display tumor genomic features consistent with
homologous repair deficiency (HRD), including large scale state transitions (LSTs),
mutational signature 3, and an enrichment for deletions flanked by sequences of (micro)
III. To explore the burden of high, moderate, and low penetrant germline alterations in HRD
genes (such as BRCA1, BRCA2, PALB2, Fanconi complex genes, ATM, CHEK2, RAD51B/C/D), mis-match
repair genes (such as MLH1, MSH2, MSH6, PMS2, EPCAM), and energy metabolism genes (such as
SDHA, SDHB, SDHC, SDHAF2, SDHD, IDH1, IDH2, and FH).
IV. To explore constitutional imprinting abnormalities associated with EP300 and IGF2 in
peripheral blood from patients with HGGs.
CHEMORADIOTHERAPY PHASE: Participants receive veliparib orally (PO) twice daily (BID) and
undergo 30 daily fractions of radiation therapy 5 days per week for 6-7 weeks in the absence
of disease progression or unacceptable toxicity.
MAINTENANCE CHEMOTHERAPY: Beginning 4 weeks after chemoradiotherapy phase, participants
receive veliparib PO BID and temozolomide PO once daily (QD) on days 1-5. Treatment repeats
every 28 days for up to 10 courses in the absence of disease progression or unacceptable