Nearly one-quarter (24%) of the 422 patients screened in the Pediatric Molecular Analysis for Therapy Choice (Pediatric MATCH) trial are eligible for treatment with at least one drug being tested in the study, the National Cancer Institute (NCI) and the NCI-supported Children’s Oncology Group (COG) said.
That’s more than double the 10% match rate projected before the opening of enrollment in the trial in 2017. The estimate was based on experience from pediatric disease-specific research studies, most of which had focused on newly diagnosed pediatric cancers as opposed to treatment-refractory tumors, as well as similar adult trials, such as Pediatric MATCH.
“One of our key goals has been to expand access to targeted therapies for pediatric cancer patients across the country, and these early results suggest that goal is within reach,” said COG study chair Will Parsons, MD, PhD, Associate Professor of Pediatrics-Oncology at Baylor College of Medicine, said in a statement. “Our study shows that we can successfully create a nationwide molecular screening trial for children, adolescents, and young adults with cancers that have been resistant to treatment.”
Added NCI study chair Nita Seibel, MD, Head of Pediatric Solid Tumor Therapeutics in the Clinical Investigations Branch of NCI’s Cancer Therapy Evaluation Program: “We’re encouraged by these early results that underscore the value of public-private collaboration in understanding and treating cancers occurring in children, adolescents, and young adults.”
NCI and COG plan to present their first update on the Pediatric MATCH study since its 2017 launch at the upcoming 2019 American Society of Clinical Oncology (ASCO) Annual Meeting, set for May 31-June 4 in Chicago. An abstract summarizing trial results to date has been published, Identification of targetable molecular alterations in the NCI-COG Pediatric MATCH trial.
NCI-COG Pediatric MATCH is the first nationwide pediatric precision oncology trial for patients with cancers that have not responded to standard treatments. The study aims to identify specific genetic alterations occurring in each patient’s cancer, match patients to drugs targeted at those alterations (regardless of cancer type), then evaluate the impact of the treatments.
Study patients were first enrolled using a screening protocol in which their tumors were sequenced and any matching alterations are identified based on previous evidence linking the alterations to targeted therapies. Patients for whom a match is found are offered enrollment in the corresponding Pediatric MATCH phase II treatment trial.
Ten different targeted therapies are being studied in Pediatric MATCH: larotrectinib, which targets NTRK; erdafitinib, FGFR; tazemetostat, EZH2 and other SWI/SNF complex genes; LY3023414, the PI3K/MTOR pathway; and selumetinib, the MAPK pathway.
Also studied are ensartinib, targeting ALK or ROS1; vemurafenib, BRAF; olaparib, defects in DNA damage repair; palbociclib, cell cycle genes; and ulixertinib, the MAPK pathway.
Investigators plan to continue to add new targeted therapies to the trial, with the goal of increasing the number of patients who could be matched to drug treatments on the study.
Protocols for four additional drugs are currently under development. Future adaptations of the trial may include testing combinations of drugs as well as immunotherapies, and optimized plans for molecular testing and assignment of patients to study treatment arms, NCI and COG said.
Alterations in 29% of Patients
Researchers completed tumor testing for 357 patients (92%). Targetable genetic alterations—mutations, fusions or gene copy number changes targeted by one of the 10 medicines in the trial—were identified in 112 (29%) patients, with 95 of those patients (24%) eligible to be assigned to one of 10 treatments available in the trial.
As of the end of 2018, 39 patients (10%) had enrolled on a Pediatric MATCH treatment trial, with additional matched patients still eligible for treatment at a later date, NCI and COG said.
The targetable alterations detected in Pediatric MATCH patients involved diverse cancer genes: most commonly RAS gene mutations, found in 16 patients; BRAF mutations or fusions, found in 14 patients; SMARCB1 mutations or deletions, found in 14 patients; NF1 mutations, found in 11 patients; and numerous alterations occurring in fewer than 10 patients each.
Targetable alterations were detected in more than 40% of patients with brain tumors and more than 25% of patients with the other cancer types tested (other solid tumors, lymphomas, and histiocytic disorders) demonstrating the utility of tumor screening for children with both common and rare cancers, according to NCI and COG.
No significant difference in the detection rate was seen between younger patients (under 12 years of age) and older children, adolescents and young adults on the study.
In addition to tumor samples, blood samples are also being sequenced as part of the study, in order to see if any of the mutations identified in each tumor are hereditary and require additional genetics evaluation for the patient and family, NCI and COG added.
A key goal of Pediatric MATCH is to add to the number of approved targeted therapies indicated for pediatric cancer. Earlier this year, ASCO included “Increase Precision Medicine Research and Treatment Approaches in Pediatric Cancers” among its nine research priorities to accelerate progress against cancer.
COG unites more than 9,000 researchers specializing in childhood cancer at more than 200 leading children’s hospitals, universities, and cancer centers across North America, Australia, New Zealand, and Europe.
NCI and COG partner on Pediatric MATCH with the FDA, biopharma companies, and institutions specializing in pediatric cancer research.