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NCI-COG Pediatric MATCH Trial Shows High Rate of Targetable Molecular Alterations

TOP - August 2019, Vol 12, No 3
Chicago, IL—Approximately one-fourth of children, adolescents, and young adults with advanced cancer were eligible for a targeted therapy after genotyping their tumors in the screening protocol of the Pediatric Molecular Analysis for Therapy Choice (MATCH) clinical trial. This rate exceeded the projected rate of 10% of patients that would be assigned to a treatment arm.

The Pediatric MATCH trial was developed and is led jointly by the National Cancer Institute (NCI) and the Children’s Oncology Group (COG). Findings from the screening protocol portion of the study were presented by Will Parsons, MD, PhD, Deputy Director, Texas Children’s Cancer and Hematology Centers, and Associate Professor, Department of Pediatrics, Hematology-Oncology, Baylor College of Medicine, Houston, at the 2019 American Society of Clinical Oncology Annual Meeting.

“This study is allowing us to evaluate targeted therapies in patients with many different cancer types—some common, some rare—so hopefully we can effectively study these agents and identify signals of activity where some of these drugs may work for our patients,” he said.

Pediatric MATCH was launched in 2017 to identify specific genetic alterations in patients with cancers that have not responded to standard treatment. Participants are enrolled into a screening protocol in which their tumors are sequenced, and if a treatment matched to any genetic alteration is found, they are offered enrollment into a Pediatric MATCH phase 2 treatment trial. There are 10 phase 2 clinical trials activated, 1 for each current single-agent targeted therapy being tested. An additional 4 targeted agents are in development, Dr Parsons noted.

Patients eligible for the screening protocol were aged between 1 and 21 years with a diagnosis of recurrent or refractory solid tumors. The treatment subprotocol called for the presence of a defined actionable mutation for that treatment arm.

As of the data cutoff of December 31, 2018, 422 patients from 93 sites had enrolled in the screening protocol, and tumor samples were obtained for 357 (92%) patients, accounting for more than 60 tumor types. Of these patients, 24% of diagnoses were central nervous system (CNS) tumors, 71% were non-CNS solid tumors, and 5% were lymphomas and histiocytoses.

Some 29% of patients had an actionable mutation detected and treatment was assigned to 24% of patients. The most frequently identified alterations were RAS mutations, BRAF mutations or fusions, SMARCB1 mutations or deletions, and NF1 mutations.

A total of 41% of patients who have been matched were enrolled in a phase 2 clinical trial thus far, “and that’s a number that will be expected to continue to increase slightly as patients who are matched are still eligible to be treated on those protocols,” Dr Parsons said. The median time from tumor sample receipt to treatment assignment is 15 days. The match rate was 46% for CNS tumors and 26% for non-CNS tumors.

The non-CNS tumors ranged from 13% for osteosarcoma to >50% for rhabdomyosarcoma, “so an appreciable detection rate across the diversity of common non-CNS tumors,” Dr Parsons said. Actionable mutations for CNS tumors were driven largely by the predominance of high-grade and low-grade astrocytomas. An actionable mutation was detected in 29 of 39 (74%) astrocytomas. “Patients with astrocytoma have been matched to 9 of the 10 available matched treatment protocols,” he said.

“Our initial experience has demonstrated that the collaborative NCI-COG Pediatric MATCH has been successfully able to create a framework in which we can efficiently collect, process, sequence, and assign patients to treatments in a nationwide clinical trial,” Dr Parsons concluded.

The investigators anticipate that the trial will enroll at least 1000 patients and that new treatment arms, possibly including combination therapies and immunotherapies, will be added.

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