The Case Study of NCI-COG Pediatric MATCH Trial

Pediatric cancer consists of a diverse group of rare diseases. The relatively small population of children with multiple disparate tumor types across various age groups presents a significant challenge for drug development program as compared to those for adults. Furthermore, modern targeted and precision cancer drug development typically are only effective in a subtype of disease, which further shrinks the targeted patient population. As a result, pediatric population is further reduced to multiple but more rare subpopulations, often defined by molecular phenotypes. The traditional design to run 1 drug trial paired with 1 biomarker is not sustainable. High screen-fail rates due to the low frequency of recurrent genomic alternations also adds to the challenges. This calls for innovative design. In this chapter, the case example of NCI-COG Pediatric MATCH trial, designed as a platform trial, is discussed in detail. The NCI-COG Pediatric MATCH trial overcomes many challenges and has created a collaborative framework for efficient collection, processing, and sequencing of refractory pediatric cancers. The study successfully facilitates evaluation of molecular-targeted agents in biomarker positive cohorts comprising a wide spectrum of childhood cancers, from common to ultra-rare. The success of the NCI-COG Pediatric MATCH sets as an example for clinical trials in pediatric and rare diseases.