The first FoundationOne®* report on splice alterations was published.
Foundation Medicine provides integrated solutions for companion diagnostics—working with our partners in biomarker-driven drug development from target discovery through approval and commercialization.
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 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 approximately 3% of lung cancer patients with cancers driven by METex14.1 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.
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.2
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.3
Foundation Medicine published further characterization of a METex14 cohort.4
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.
July 15, 2021 – FoundationOne®Liquid CDx is approved by the FDA as the only blood-based CGP companion diagnostic (CDx) for Tabrecta™ (capmatinib).
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.5
Our FDA-approved portfolio of both CGP tissue- and blood-based tests are now approved as the only CDx for Tabrecta® (capmatinib) in identifying advanced non-small cell lung cancer (NSCLC) patients having mutations that lead to METex14 skipping mutations and offers the highest number of CDx indications in NSCLC.
*FoundationOne® is a previous version and different from FoundationOne®CDx. For concordance results between these two tests, please see our full intended use at www.F1CDxLabel.com 1Frampton GM, Ali SM, Rosenzweig M, et al. Activation of MET via diverse exon 14 splicing alterations occurs in multiple tumor types and confers clinical sensitivity to MET inhibitors. Cancer Discov. 2015;5(8):850-859. doi:10.1158/2159-8290. CD-15-0285
2Jenkins 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.
3Frampton 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)
4Schrock, 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.
5Wolf, J., et al. Capmatinib in MET Exon 14-Mutated or MET-Amplified Non-Small-Cell Lung Cancer. The New England Journal of Medicine, 383(10), 944–957. https://doi.org/10.1056/NEJMoa2002787
Tabrecta™ is a trademark of Novartis AG.
FoundationOne®CDx is a qualitative next-generation sequencing based in vitro diagnostic test for 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
FoundationOne®Tracker is a clinical test performed exclusively as a laboratory service. This test has not been cleared or approved by the U.S. Food and Drug Administration (FDA). FoundationOne Tracker is a personalized assay for oncology that is based on patient-specific somatic variants (substitutions and short insertions/deletions) identified from baseline tumor tissue testing and used to detect and longitudinally measure plasma circulating tumor DNA (ctDNA) abundance as a biomarker for tumor burden. Treatment decisions are the responsibility of the treating physician. ctDNA detection sensitivity may be limited if blood collection occurs within two weeks of surgery or while a patient is on therapy. A negative test result does not definitively indicate the absence of cancer. This test is not designed to detect or report germline variation, nor does it infer hereditary cancer risk for a patient. This test is designed to detect ctDNA from the assayed tumor only; new primary tumors will not be detected. This test is expected to have limited sensitivity in some cancer types due to limited ctDNA shed.
FoundationOne Liquid CDX
FoundationOne®Liquid CDx is for prescription use only and is a qualitative next-generation sequencing based in vitro diagnostic test for cancer patients with solid tumors. The test analyzes 324 genes utilizing circulating cell-free DNA and is FDA-approved to report short variants in 311 genes and as a companion diagnostic to identify patients who may benefit from treatment with specific therapies (listed in Table 1 of the Intended Use) 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. When considering eligibility for certain therapies for which FoundationOne Liquid CDx is a companion diagnostic, testing of plasma is only appropriate where tumor tissue is not available. Patients who are negative for other companion diagnostic mutations should be reflexed to tumor tissue testing and mutation status confirmed using an FDA-approved tumor tissue test, if feasible. For the complete label, including companion diagnostic indications and complete risk information, please visit www.F1LCDxLabel.com.