%0 Clinical Trial
%T Olaparib for childhood tumors harboring defects in DNA damage repair genes: arm H of the NCI-COG Pediatric MATCH trial.
%A Glade Bender JL
%A Pinkney K
%A Williams PM
%A Roy-Chowdhuri S
%A Patton DR
%A Coffey BD
%A Reid JM
%A Piao J
%A Saguilig L
%A Alonzo TA
%A Berg SL
%A Ramirez NC
%A Fox E
%A Weigel BJ
%A Hawkins DS
%A Mooney MM
%A Takebe N
%A Tricoli JV
%A Janeway KA
%A Seibel NL
%A Parsons DW
%J Oncologist
%V 29
%N 7
%D 2024 Jul 5
%M 38815151
%F 5.837
%R 10.1093/oncolo/oyae096
%X <B>BACKGROUND: </B>The National Cancer Institute-Children's Oncology Group Pediatric Molecular Analysis for Therapy Choice (MATCH) precision oncology platform trial enrolled children aged 1-21 years with treatment-refractory solid tumors and predefined actionable genetic alterations. Patients with tumors harboring alterations in DNA damage repair (DDR) genes were assigned to receive olaparib.<BR><B>METHODS: </B>Tumor and blood samples were submitted for centralized molecular testing. Tumor and germline sequencing were conducted in parallel. Olaparib was given twice daily for 28-day cycles starting at a dose 30% lower than the adult recommended phase 2 dose (RP2D). The primary endpoint was the objective response.<BR><B>RESULTS: </B>Eighteen patients matched (1.5% of those screened) based on the presence of a deleterious gene alteration in BRCA1/2, RAD51C/D, or ATM detected by tumor sequencing without germline subtraction or analysis of loss of heterozygosity (LOH). Eleven (61%) harbored a germline mutation, with only one exhibiting LOH. Six patients enrolled and received the olaparib starting dose of 135 mg/m2/dose. Two participants were fully evaluable; 4 were inevaluable because <85% of the prescribed dose was administered during cycle 1. There were no dose-limiting toxicities or responses. Minimal hematologic toxicity was observed.<BR><B>CONCLUSIONS: </B>Most DDR gene alterations detected in Pediatric MATCH were germline, monoallelic, and unlikely to confer homologous recombination deficiency predicting sensitivity to olaparib monotherapy. The study closed due to poor accrual.<BR><B>BACKGROUND: </B>NCT03233204. IRB approved: initial July 24, 2017.