Pediatric MATCH Trial Opens Enrollment

Two years after the launch of the NCI's massive Molecular Analysis for Therapy Choice (MATCH) trial for adults, the NCI-backed Children's Oncology Group (COG) has begun enrolling children and adolescents with a wide range of tumor types for a complementary basket study.

Dubbed NCI-COG Pediatric MATCH, the study is designed for those ages 1 to 21 who have solid tumors, non-Hodgkin lymphomas, or histiocytic disorders that harbor targetable genetic mutations and have progressed after standard therapy.

Over the next 3 to 4 years, clinicians at close to 200 sites across the United States will collect tumor biopsies from at least 1,000 pediatric patients. DNA and RNA processing will take place at the Nationwide Children's Hospital in Columbus, OH—home to the COG Biopathology Center—while technicians at the NCI's Frederick National Laboratory for Cancer Research in Frederick, MD, and The University of Texas MD Anderson Cancer Center in Houston will run the sequencing assays needed to detect molecular alterations in more than 160 cancer-linked genes. Peripheral blood samples will also be analyzed and compared to the tumor samples to determine whether any DNA mutations were inherited or arose somatically.

Patients with certain genetic alterations would then receive one of seven drugs. These include inhibitors of ALK, BRAF, EZH2, MEK, PARP, PI3K/mTOR, and TRK, none of which are FDA approved for use in children and adolescents. (Two are approved for use in adults.) Other drugs, including ones directed at FGFR and CDK4/6, will likely be added within the next year, according to Nita Seibel, MD, head of pediatric solid tumor therapeutics at the NCI in Bethesda, MD. Discussions are ongoing with pharmaceutical companies about adding three more.

The trial's Target and Agent Prioritization Committee recommended the first batch of targeted therapies after systematically reviewing available preclinical and clinical data, including which drug classes had genomic biomarkers (J Natl Cancer Inst 2017;109:djw274). Committee members—led by co-chairs Katherine Janeway, MD, of Dana-Farber Cancer Institute in Boston, MA, and Yoon-Jae Cho, MD, of Oregon Health & Science University in Portland—evaluated several factors, such as data on the link between targets and agent activity, the known frequency of mutations in pediatric cancers, and toxicities documented in adults—to winnow the list from 15 to seven drugs. “We tried to be as comprehensive in our consideration as possible,” says Cho.

According to trial co-chair Will Parsons, MD, PhD, from Texas Children's Hospital and Baylor College of Medicine in Houston, TX, the trial is not necessarily powered to generate the amount of data needed for regulatory approvals. After all, only about 10% of screened patients are expected to have an alteration targeted by one of the study drugs. “Really, we're just trying to look for agents in which we can see a signal of activity,” Parsons says. However, if any agent does look promising, he notes, “we do have plans for small expansion cohorts.” –Elie Dolgin

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