APEC1621 SC - NCI-COG Pediatric MATCH (Molecular Analysis for Therapy Choice) Screening Protocol

Abstract The Pediatric MATCH (Molecular Analysis for Therapy Choice) study, (referred to as Pediatric MATCH in the remainder of this document), will match targeted agents with specific molecular changes identified using genomic sequencing technologies in refractory/recurrent tumors from children and adolescents with cancer. Pediatric MATCH will build upon experience from the adult NCI MATCH clinical trial. Pediatric MATCH will be a national trial under a single IND and will be led by NCI and the Children’s Oncology Group (COG), a member of the NCI National Clinical Trial Network (NCTN). Pediatric MATCH will employ an analytically validated next-generation sequencing targeted assay of more than 4,000 different mutations (SNVs, indels, copy number alterations, and gene fusions) across more than 140 genes. This assay will be coupled to a computer algorithm that uses pre-existing definitions and prioritization of target-agent pairs to assign patients by actionable mutation results to a targeted treatment. As of Amendment #4: Starting in 2022, Pediatric MATCH will move to a new screening model, called Stage 2, in which tumor molecular profiling reports from CLIA-certified clinical laboratories are reviewed to determine molecular eligibility to Pediatric MATCH treatment protocols. Centralized tumor testing will no longer be performed as part of the study. The Stage 2 review process will utilize the same definitions for clinical actionability of tumor mutations as used throughout Pediatric MATCH. The primary endpoint for Pediatric MATCH will be objective response rate. The study will use a trial design with the flexibility to open and close arms. The study drugs included in this trial will include agents that have at least an adult recommended phase 2 dose and that have shown some activity against tumors with a particular genetic alteration(s). Patients with recurrent or refractory tumors enrolled on study will have tumor molecular profiling reports that are believed (in the opinion of the treating clinician) to confer eligibility to a Pediatric MATCH treatment arm. If confirmed by Pediatric MATCH review, the patient will be offered treatment on Pediatric MATCH.