Target and Agent Prioritization for the Children's Oncology Group-National Cancer Institute Pediatric MATCH Trial

Over the past decades, outcomes for children with cancer have improved dramatically through serial clinical trials based in large measure on dose intensification of cytotoxic chemotherapy for children with high-risk malignancies. Progress made through such dose intensification, in general, is no longer yielding further improvements in outcome. With the revolution in sequencing technologies and rapid development of drugs that block specific proteins and pathways, there is now an opportunity to improve outcomes for pediatric cancer patients through mutation-based targeted therapeutic strategies. The Children's Oncology Group (COG), in partnership with the National Cancer Institute (NCI), is planning a trial entitled the COG-NCI Pediatric Molecular Analysis for Therapeutic Choice (Pediatric MATCH) protocol utilizing an umbrella design. This protocol will have centralized infrastructure and will consist of a biomarker profiling protocol and multiple single-arm phase II trials of targeted therapies. Pediatric patients with recurrent or refractory solid tumors, lymphomas, or histiocytoses with measurable disease will be eligible. The Pediatric MATCH Target and Agent Prioritization (TAP) committee includes membership representing COG disease committees, the Food and Drug Administration, and the NCI. The TAP Committee systematically reviewed target and agent pairs for inclusion in the Pediatric MATCH trial. Fifteen drug-target pairs were reviewed by the TAP Committee, with seven recommended for further development as initial arms of the Pediatric MATCH trial. The current evidence for availability, efficacy, and safety of targeted agents in children for each class of mutation considered for inclusion in the Pediatric MATCH trial is discussed in this review.