The following article features coverage from the American Society of Clinical Oncology 2019 meeting. Click here to read more of Cancer Therapy Advisor‘s conference coverage.

Based on the results of DNA and RNA sequencing of their tumor specimens, approximately one-quarter of the more than 400 patients aged 1 to 21 years with relapsed or refractory advanced solid tumors, non-Hodgkin lymphomas, or histiocytic disorders enrolled in the screening portion of the National Cancer Institute/Cancer Oncology Group (NCI/COG) Pediatric MATCH trial (Targeted Therapy Directed by Genetic Testing in Treating Pediatric Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphomas, or Histiocytic Disorders; ClinicalTrials.gov Identifier: NCT03155620) were deemed eligible to receive treatment with at least 1 molecularly targeted therapy being evaluated in the phase 2 portion of the study.1,2

The NCI-COG Pediatric MATCH study, “the first nationwide pediatric precision oncology trial for patients with cancer that have not responded to standard treatments,”is a multicenter study being conducted at COG sites across the US, and involves collaborations between the NCI, COG, the US Food and Drug Administration (FDA), pharmaceutical companies, and other groups.2

Given the low number of targeted therapies approved by the FDA for the treatment of children with cancer, the American Society of Clinical Oncology (ASCO) has designed investigations of precision oncology approaches in this population as “a critical research priority.”2

Patients are initially enrolled in the screening portion of the study, in which DNA and RNA sequencing of formalin-fixed paraffin-embedded tumor specimens that interrogates more than 160 genes is performed.

Independent of tumor type, study participants with somatic mutations in FGFR1, FGFR2, FGFR3, or FGFR4, EZH2, SMARCB1, or SMARCA4, TSC1, TSC2, or PI3K/mTOR, ALK or ROS1, BRAF V600, ATM, BRCA1, BRCA2, RAD51C, RAD51D, as well as those with tumors characterized by an NTRK1, NTRK2, or NTRK3 gene fusion, or by a mutation in the MAPK pathway or that is classified as Rb-positive and having alterations in cell-cycle genes, are considered eligible for enrollment in 1 of 10 phase 2 studies involving single-agent targeted therapy.

The primary outcome measure of the study is objective response as assessed by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. Secondary study outcome measures include safety and progression-free survival. In addition, another outcome measure involves an evaluation of the spectrum and frequencies of cancer susceptibility mutations in this population through germline testing of peripheral blood specimens.

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Beyond the relatively high percentage of study participants found to have tumors characterized by an actionable molecular alteration, confirmed sequencing results were obtained in 92% of patients for whom this testing was attempted.2

Similar rates of actionable molecular alterations were identified in the tumors of patients younger than 12 years compared with those older than 12 years.1 Interestingly, tumor sequencing results revealed that of the patients with brain cancer, more than 40% with successful test results had at least 1 of the molecular alterations identified in the study.2

“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,” said COG Study Chair Will Parsons, MD, PhD, associate professor of pediatrics-oncology at Baylor College of Medicine in Houston, Texas. “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.”2

Moving forward, it is anticipated that the Pediatric MATCH study will enroll at least 1000 patients and that new treatment arms, possibly including combination therapies and immunotherapies, will be added.

Read more of Cancer Therapy Advisor‘s coverage of ASCO’s annual meeting by visiting the conference page.

References

  1. Parsons DW, Janeway KA, Patton D, et al. Identification of targetable molecular alterations in the NCI -COG Pediatric MATCH trial. To be presented at the: 2019 American Society of Clinical Oncology Annual Meeting. Chicago, IL. May 31 to June 4, 2019: Abstract 10011.
  2. Pediatric MATCH trial finds more frequent targetable genetic alterations in pediatric cancers than predicted. https://www.asco.org/about-asco/press-center/news-releases/pediatric-match-trial-finds-more-frequent-targetable-genetic. Accessed May 20, 2019.