Patients HCP
This site is for US Health Care Professionals only
Banner background
About Testing
Companion Diagnostics

Why test for biomarkers in mNSCLC?

~1 in 2 patients with mNSCLC may have an actionable mutation that can be treated with a targeted therapy7-16*

Actionable mutations in mNSCLC

 

PD-L1 IS AN IMMUNE CHECKPOINT PROTEIN, NOT AN ACTIONABLE MUTATION17

  • METex14 has a prevalence of ~3%, representing ~4,000-5,000 patients with mNSCLC per year in the United States18,19†

  • Patients with METex14 in mNSCLC face a poor prognosis20-22

    • Many of these patients may have bone, liver, and brain metastases, which are associated with poor outcomes
       

Capmatinib (TABRECTA® tablets) is an NCCN Guidelines®CATEGORY 2A (PREFERRED) FIRST-LINE TREATMENT option for patients with METex14-positive mNSCLC1‡



When to test

To inform up-front treatment planning, test every patient with mNSCLC at diagnosis

According to the NCCN Guidelines for NSCLC, clinicians should obtain biomarker test results in appropriate patients at diagnosis of mNSCLC, prior to administering a first-line therapy, if feasible.1

  • Accurate detection of mutations leading to METex14 in mNSCLC could facilitate timely intervention23

  • Identifying METex14 in mNSCLC may unlock the option for first-line targeted therapy with TABRECTA2

 

 

How to test

Comprehensive genomic profiling may identify a wide range of actionable mutations with 1 test24,25

Single-gene testing for multiple biomarkers sequentially may:

  • Result in longer turnaround times and increase the risk of tissue exhaustion, potentially necessitating a rebiopsy26,27

  • Fail to identify clinically relevant genomic alterations, narrowing the treatment options for patients28
     

NCCN recommendation


Broad molecular profiling is STRONGLY ADVISED BY NCCN for the identification of actionable mutations in eligible patients with mNSCLC1§
 

ALK, anaplastic lymphoma kinase; BRAF, v-raf murine sarcoma viral oncogene homolog B1; EGFR, epidermal growth factor receptor; ERBB2, v-erb-b2 avian erythroblastic oncogene homolog 2; HER2, human epidermal growth factor receptor 2; KRAS, Kirsten rat sarcoma; MET, mesenchymal-epithelial transition; METex14, MET exon 14 skipping; mNSCLC, metastatic non-small cell lung cancer; NTRK, neurotrophic tyrosine receptor kinase;
RET, rearranged during transfection; ROS1, ROS proto-oncogene 1, receptor tyrosine kinase.
NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application.
*Prevalence rates are in accordance with those from The Cancer Genome Atlas (TCGA) Research Network, a joint effort between the National Cancer Institute and the National Human Genome Research Institute. To access the latest TCGA data, please visit: cancer.gov/about-nci/organization/ccg/research/structural-genomics/tcga.
†This calculation is based on a 3% prevalence rate and mNSCLC-specific incidence and recurrence data from Kantar Health.
‡See the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for detailed recommendations, including other options.
§The NCCN Guidelines for NSCLC provide recommendations for individual biomarkers that should be tested and recommend testing techniques but do not endorse any specific commercially available biomarker assays or commercial laboratories.

FoundationOne®CDx and FoundationOne®Liquid CDx are the FDA-approved companion diagnostics for TABRECTA® (capmatinib) tablets

Tissue-based FoundationOne®
CDx

 

FoundationOne®CDx specimen kit

FoundationOne®CDx analyzes DNA isolated from FFPE tumor tissue specimens.29

Blood-based FoundationOne®Liquid CDx
 

FoundationOne®Liquid CDx specimen kit

FoundationOne®Liquid CDx analyzes DNA extracted from plasma.30

  • In a retrospective analysis, FoundationOne®CDx demonstrated a 99% positive percentage agreement (n=72/73) with the RNA-based RT-PCR clinical trial assay (CTA) that confirmed METex14 in patients taking TABRECTA® (capmatinib) tablets in GEOMETRY mono-12,*,†

    • Negative percentage agreement was 100% (125/125)29‡

  • In a retrospective analysis, FoundationOne®Liquid CDx demonstrated a 71% positive percentage agreement (n=55/78) with the CTA that confirmed METex14 in patients taking TABRECTA® (capmatinib) tablets in GEOMETRY mono-131,§,||

    • Negative percentage agreement was 100% (72/72)

99% positive percentage agreement (72/73)
71% positive percentage agreement (55/78)

  • Foundation Medicine results have a typical turnaround time of 8.8 days (FoundationOne®CDx) and 7.8 days (FoundationOne®Liquid CDx) from receipt of specimen32,33

  • FoundationOne®CDx and FoundationOne®Liquid CDx are covered by Original Medicare and Medicare Advantage for qualifying beneficiaries34

  • Foundation Medicine offers in-home blood draw with mobile phlebotomy to support broader access to FoundationOne®Liquid CDx at no additional cost35
     

Reflex to an FDA-approved tissue test in the event of negative findings on blood-based test results, if feasible2


FoundationOne®CDx and FoundationOne®Liquid CDx are qualitative next-generation sequencing based in vitro diagnostic tests for advanced cancer patients with solid tumors and are for prescription use only. FoundationOne CDx utilizes FFPE tissue and analyzes 324 genes as well as genomic signatures. FoundationOne Liquid CDx analyzes 324 genes utilizing circulating cell-free DNA and is FDA-approved to report short variants in 311 genes. The tests are companion diagnostics to identify patients who may benefit from treatment with specific therapies in accordance with the 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 tests 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 testing with FoundationOne CDx when archival tissue is not available which may pose a risk. 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 tested with FoundationOne Liquid CDx and 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 important risk information, please visit www.F1CDxLabel.com ↗ and www.F1LCDxLabel.com. ↗

 

Clinical Utility Data
 

Clinical utility data in a retrospective analysis of patients with METex14 as confirmed by FoundationOne®Liquid CDx (n=55)31
 

  • Clinical utility was analyzed in tissue diagnostic–positive patients from cohorts 4 and 5b who also tested positive for METex14 with FoundationOne®Liquid CDx

  • This analysis of clinical utility was not designed to demonstrate the therapeutic effect or superiority of testing modalities
     

Clinical utility data of FoundationOne®Liquid CDx in treatment-naive patients (Cohort 5b, n=16)36

81% ORR (95% CI, 54.4-96; n=13/16). 20.3 Months mDOR (95% CI, 4.2-NE; n=13).

Of the 28 patients in Cohort 5b, 26 met the recommended sample requirement (≥30 ng) for retesting using FoundationOne®Liquid CDx. Twenty-five samples were determined to be valid, out of which 16 were confirmed to be METex14+ using FoundationOne®Liquid CDx. Thirteen of 16 patients had either complete response or partial response, and DOR was evaluated for those 13 patients only.31
 

Clinical utility data of FoundationOne®Liquid CDx in previously treated patients (Cohort 4, n=39)36

51% ORR (95% CI, 34.8-67.6, n=20/39). 9.8 Months mDOR (95% CI, 4.2-19.5; n=20).

Of the 69 patients in Cohort 4, 55 met the recommended sample requirement (≥30 ng) for retesting using FoundationOne®Liquid CDx. Fifty-three samples were determined to be valid, out of which 39 were confirmed to be METex14+ using FoundationOne®Liquid CDx. Twenty of 39 patients had either complete response or partial response, and DOR was evaluated for those 20 patients only.31  
 

Clinical utility data of FoundationOne®Liquid CDx: Noncomparative analysis of median PFS and OS
 

Due to the nonrandomized, noncomparative nature of the study, PFS and OS results are difficult to interpret. No statistical tests were made for PFS and OS, as there was no comparator arm. PFS and OS results are based on an interim analysis; results are subject to change pending longer trial follow-up.  
 

In treatment-naive patients:

  • 12.4-month median PFS (95% CI, 4.5-NE; n=16)36

  • 17.9-month median OS (95% CI, 9.8-NE; n=16)36


In previously treated patients:

  • 5.4-month median PFS (95% CI, 4-6.9; n=39)36

  • 11.5-month median OS (95% CI, 5.4-23.3; n=39)36

Information on the FDA-approved tests for the detection of METex14 in mNSCLC is available at:


CDx, companion diagnostic; FFPE, formalin-fixed paraffin-embedded; mDOR, median duration of response; NE, not estimable; OS, overall survival; ORR, overall response rate; PFS, progression-free survival; RT-PCR, reverse transcription-polymerase chain reaction.  
*The primary concordance analysis was conducted on 204 samples (78 positive and 126 negative). The denominator is the total number of evaluable samples, and the numerator is the number of patients with agreement.29  
†Of 78 specimens available to be retested, only 73 were evaluable.  
‡Of 126 specimens available to be retested, only 125 were evaluable.  
§The primary concordance analysis was conducted on 159 samples (81 positive and 78 negative). The denominator is the total number of valid samples, and the numerator is the number of patients with agreement.  
||Of the 81 patients who were CTA positive and retested with FoundationOne®Liquid CDx, 55 results were positive, 23 were discordant (ie, negative), and 3 were invalid.  
Of the 78 patients who were CTA negative and retested with FoundationOne®Liquid CDx, 72 results were negative, 0 were positive, and 6 were invalid.

References: 1. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Non-Small Cell Lung Cancer V.2.2023. © National Comprehensive Cancer Network, Inc. 2023. All rights reserved. Accessed March 28, 2023. To view the most recent and complete version of the guideline, go online to NCCN.org. 2. Tabrecta. Prescribing information. Novartis Pharmaceuticals Corp. 3. Data on file. Study CINC280A2201. Novartis Pharmaceuticals Corp; 2021. 4. Data on file. Study CINC280A2201. Novartis Pharmaceuticals Corp; 2019. 5. Wolf J, Seto T, Han J-Y, et al. N Engl J Med. 2020;383(10):944-957. 6. Wolf J, Seto T, Han J-Y, et al. N Engl J Med (suppl). doi:10.1056/NEJMoa2002787 7. Shea M, Costa DB, Rangachari D. Ther Adv Respir Dis. 2016;10(2):113-129. 8. Awad MM, Oxnard GR, Jackman DM, et al. J Clin Oncol. 2016;34(7):721-730. 9. Nadal E, Chen G, Prensner J, et al. J Thorac Oncol. 2014;9(10):1513-1522. 10. Scheffler M, Ihle MA, Hein R, et al. J Thorac Oncol. 2019;14(4):606-616. 11. Oxnard GR, Lo PC, Nishino M, et al. J Thorac Oncol. 2013;8(2):179-184. 12. Arcila ME, Nafa K, Chaft JE, et al. Mol Cancer Ther. 2013;12(2):220-229. 13. Brustugun OT, Khattak AM, Trømborg AK, et al. Lung Cancer. 2014;84(1):36-38. 14. Vaishnavi A, Capelletti M, Le AT, et al. Nat Med. 2013;19(11):1469-1472. 15. D’Angelo SP, Pietanza MC, Johnson ML, et al. J Clin Oncol. 2011;29(15):2066-2070. 16. Pillai RN, Behera M, Berry LD, et al. Cancer. 2017;123(21):4099-4105. 17. NCI Dictionary of Cancer Terms. PD-L1. Accessed March 28, 2023. https://www.cancer.gov/publications/dictionaries/cancer-terms/def/pd-l1 18. Vuong HG, Ho ATN, Altibi AMA, Nakazawa T, Katoh R, Kondo T. Lung Cancer. 2018;123:76-82. 19. Data on file. Novartis Calculation. Kantar Health. Updated December 15, 2018. My.khapps.com 20. Hsu F, De Caluwe A, Anderson D, Nichol A, Toriumi T, Ho C. Curr Oncol. 2017;24(4):228-233. 21. Awad MM, Leonardi GC, Kravets S, et al. Lung Cancer. 2019;133:96-102. 22. Awad MM, Leonardi GC, Kravets S, et al. Lung Cancer (suppl). doi.org/10.1016/j.lungcan.2019.05.011 23. Kim EK, Kim KA, Lee CY, et al. Clin Lung Cancer. 2019;20(1):e123-e132. 24. Hinrichs JW, van Blokland WT, Moons MJ, et al. Am J Clin Pathol. 2015;143(4):573-578. 25. Yu TM, Morrison C, Gold EJ, Tradonsky A, Layton AJ. Clin Lung Cancer. 2019;20(1):20-29. 26. Pennell NA, Mutebi A, Zhou Z-Y. JCO Precis Oncol. 2019. 27. Drilon A, Wang L, Arcila ME, et al. Clin Cancer Res. 2015;21(16):3631-3639. 28. Ali SM, Hensing T, Schrock AB, et al. Oncologist. 2016;21(6):762-770. 29. Foundation Medicine, Inc. FoundationOne®CDx technical information. Accessed March 28, 2023. https://assets.ctfassets.net/w98cd481qyp0/41rJj28gFwtxCwHQxopaEb/70c6c95b4edfe8c18c27c2e2461e5c28/FoundationOne_CDx_Label_Technical_Info.pdf 30. Foundation Medicine, Inc. FoundationOne®Liquid CDx technical information. Accessed March 28, 2023. https://assets.ctfassets.net/w98cd481qyp0/3a8jFw3KUjIU3RWPdcT9Ax/52303a23af6cfbb7a899c90fcb4c22df/FoundationOne_Liquid_CDx_Label_Technical_Info.pdf 31. Data on file. Study CINC280A2201, Plasma CDx. Novartis Pharmaceuticals Corp; 2021. 32. Foundation Medicine, Inc. What is FoundationOne CDx? Accessed March 28, 2023. https://www.foundationmedicine.com/test/foundationone-cdx 33. Foundation Medicine, Inc. What is FoundationOne®Liquid CDx? Accessed March 28, 2023. https://www.foundationmedicine.com/test/foundationone-liquid-cdx 34. Foundation Medicine, Inc. Billing and financial assistance. Accessed March 28, 2023. https://www.foundationmedicine.com/resource/billing-and-financial-assistance 35. Foundation Medicine, Inc. Foundation Medicine mobile phlebotomy. Accessed March 28, 2023. https://assets.ctfassets.net/w98cd481qyp0/4jVqxTjDfcHxzGmzwyKZCb/ec459c0296895b15101ac1a21e066f94/Mobile_Phlebotomy_Overview_HCP.pdf 36. Data on file. Study CINC280A2201, Statistical Analysis Results - Efficacy Analysis on F1LCDx Positive Patients for ASCO2021. Novartis Pharmaceuticals Corp; 2021.