From Biomarker Discovery to Companion Diagnostic—an end-to-end approach to precision medicine
Foundation Medicine is dedicated to working throughout the entire process to help produce results for biopharma partners, physicians, and patients alike. We are also dedicated to researching and publishing throughout the entire development and commercialization of companion diagnostic claims. Explore a timeline of our documented progress of one such claim below.
FoundationOne CDx was approved to identify mutations that lead to MET exon 14 skipping in advanced non-small cell lung cancer (NSCLC) and match patients with a new targeted therapy, which was approved in parallel. This simultaneous approval presents a new treatment option for the 2-3% of lung cancer patients with cancers driven by METex14. It is another significant step forward on the path of progress in lung cancer treatment, which demonstrates the power of cancer precision medicine in action and the role that comprehensive genomic profiling plays.
The first FoundationOne®* report on splice alterations was published.
Foundation Medicine identified a statistical signal for a MET splice variant enriched in NSCLC, elevated MET exon 14 (METex14) splice variants to the front page of the FoundationOne® report and associated them with crizotinib.
We performed outreach to physicians for recent patients whose Foundation Medicine reports showed METex14 alterations.
Foundation Medicine published on the landscape of METex14 alterations (with Novartis co-authors), including case reports demonstrating response to crizotinib and capmatinib.1
Data mining revealed that variants affecting splicing of the MET gene were occurring much more frequently in lung cancer than any other tumor type.
After examining all genomic alterations in our database, results indicated that METex14 mutations were clinically and therapeutically relevant oncogenic drivers in ~3% of NSCLC samples.2
We published these findings in 2015 and presented at ASCO that year, creating broader interest in the role of METex14 mutations in lung cancer.2
Foundation Medicine published further characterization of a METex14 cohort.3
Development of a targeted therapy for METex14 skipping mutations progresses with Novartis-sponsored clinical trials; Foundation Medicine partners to define biomarker and develop CDx.
May 6, 2020 FoundationOne®CDx is FDA-approved as the companion diagnostic test for TABRECTA™ (capmatinib), the first targeted therapy for mutations that lead to METex14 skipping.
The GEOMETRY-mono 1 trial has demonstrated that patients with advanced NSCLC, who harbor mutations that lead to METex14 skipping that were treated with capmatinib, saw significant improvement in overall response rate (ORR) in both the treatment-naïve group and pre-treated group.4
FoundationOne CDx, the first FDA-approved comprehensive genomic profiling (CGP) test for all solid tumors with Medicare coverage for qualifying patients†, is the first and only FDA-approved companion diagnostic test for TABRECTA™ (capmatinib), a kinase inhibitor that was approved in parallel for locally advanced or metastatic non-small cell lung cancer (NSCLC) patients harboring these mutations.
Reports—Following approval, FoundationOne CDx reports began including these therapies on page 1 in accordance with the associated FDA-approved indications.
Outreach—We notified physicians if at least one of their patients who received FoundationOne CDx tissue-based testing within the last 24 months was identified to have a mutation that leads to METex14 skipping, and thus, may meet the eligibility criteria for treatment with capmatinib.
1Jenkins RW, Oxnard GR, Elkin S, Sullivan EK, Carter JL, Barbie DA. Response to crizotinib in a patient with lung adenocarcinoma harboring a MET splice site mutation. Clin Lung Cancer 2015 Feb 7.
2Frampton GM. Comprehensive genomic profiling (CGP) of advanced cancers to identify MET exon 14 alterations that confer sensitivity to MET inhibitors. J Clin Oncol 2015;33(suppl; abstr 11007)
3Schrock, Alexa B. et al. Characterization of 298 Patients with Lung Cancer Harboring MET Exon 14 Skipping Alterations. J Thorac Oncol. 2016 Sep;11(9):1493-502.
4Wolf J, Seto T, Han J, et al. Capmatinib in METex14-mutated advanced non-small cell lung cancer (NSCLC): Efficacy data from the phase II GEOMETRY mono-1 study. Abstract 9004. Presented at: 2019 ASCO Annual Meeting; May 31-June 4, 2019; Chicago, IL
*FoundationOne CDx is the next evolution of FoundationOne, our pioneering laboratory-developed test (LDT). FoundationOne CDx is approved by the FDA. FoundationOne is performed in our CLIA-certified and CAP-accredited laboratory.
†Medicare and Medicare Advantage members have coverage of FoundationOne CDx in accordance with the Centers for Medicare and Medicaid Services (CMS) national coverage determination (NCD) criteria.
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Important Safety Information
FoundationOne®CDx is a qualitative next-generation sequencing based in vitro diagnostic test for advanced cancer patients with solid tumors and is for prescription use only. The test analyzes 324 genes as well as genomic signatures including microsatellite instability (MSI) and tumor mutational burden (TMB) and is a companion diagnostic to identify patients who may benefit from treatment with specific therapies in accordance with the approved therapeutic product labeling. Additional genomic findings may be reported and are not prescriptive or conclusive for labeled use of any specific therapeutic product. Use of the test does not guarantee a patient will be matched to a treatment. A negative result does not rule out the presence of an alteration. Some patients may require a biopsy. For the complete label, including companion diagnostic indications and important risk information, please visit www.F1CDxLabel.com.