Important Safety Information:


Interstitial Lung Disease (ILD)/Pneumonitis.
ILD/pneumonitis, which can be fatal, occurred in patients treated with TABRECTA® (capmatinib) tablets. ILD/pneumonitis occurred in 4.5% of patients trea...

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Indication
TABRECTA® (capmatinib) tablets is indicated for the treatment of adult patients with metastatic non-small cell lung cancer (NSCLC) whose tumors have a mutation that leads to mesenchymal-epithelial transition (MET) exon 14 skipping as detected by an FDA-approved test.

This indication is approved under accelerated approval based on overall response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.

Testing for MET Exon 14 Skipping in mNSCLC

Why Test

Identifying METex14 in mNSCLC may unlock the option for first-line targeted therapy with TABRECTA® (capmatinib) tablets1

Nearly 1 in 2 patients with mNSCLC may have an actionable mutation.2-10*
  • METex14 occurs in approximately 3%11
  • Oncogenic drivers are often mutually exclusive and define specific molecular subtypes of NSCLC12,13
Actionable mutations in mNSCLC

The complex biological structure of METex14 requires a test that is specifically designed for its detection14,15

Various point mutations leading to skipping of exon 14 of MET

MET normally participates in signaling pathways involved in embryonic development, wound healing, and tissue regeneration.18

  • Exon 14 skipping results in a MET protein that lacks a critical regulatory domain, leading to decreased MET degradation and prolonged activation of downstream signaling pathways, which are associated with oncogenic transformation and metastasis17,19

  • A broad range of molecular alterations may lead to METex1417

 

MET, mesenchymal-epithelial transition; METex14, MET exon 14 skipping; mNSCLC, metastatic non-small cell lung cancer; mRNA, messenger RNA.
*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.


When to Test

Test for METex14 upon diagnosis when a patient presents with mNSCLC1,14

  • Accurate detection of mutations leading to METex14 in mNSCLC could facilitate timely intervention20

How to Test

Comprehensive genomic profiling is a reliable way to identify actionable mutations in mNSCLC with 1 sample21,22

  • Single-gene testing for multiple biomarkers sequentially can result in longer turnaround times and increase the risk of tissue exhaustion, potentially necessitating a rebiopsy23,24
  • Single-gene testing may also fail to identify clinically relevant genomic alterations, narrowing the treatment options for patients24,25

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

Foundation Medicine logo

Tissue-based FoundationOne®CDx analyzes DNA isolated from FFPE tumor tissue specimens26

FoundationOne®CDx specimen kit

Blood-based FoundationOne®Liquid CDx analyzes DNA extracted from plasma27

FoundationOne®Liquid CDx specimen kit
  • Foundation Medicine results have a typical turnaround time of ≤10 days from receipt of specimen28

  • FoundationOne®CDx and FoundationOne®Liquid CDx are covered by Original Medicare and Medicare Advantage for qualifying beneficiaries29

  • Foundation Medicine offers in-home blood draw with mobile phlebotomy through its partner, ExamOne®, to support broader access to FoundationOne®Liquid CDx at no additional cost30

 

Reflex to tissue biopsy for negative findings on blood-based test results, if feasible1

Only patients with METex14 are eligible for biomarker-driven therapy with TABRECTA1

 

 

CDx, companion diagnostic; FFPE, formalin-fixed paraffin-embedded.

 

References: 1. Tabrecta [prescribing information]. East Hanover, NJ: Novartis Pharmaceuticals Corp; 2022. 2. Shea M, Costa DB, Rangachari D. Management of advanced non-small cell lung cancers with known mutations or rearrangements: latest evidence and treatment approaches. Ther Adv Respir Dis. 2016;10(2):113-129. 3. Awad MM, Oxnard GR, Jackman DM, et al. MET exon 14 mutations in non-small-cell lung cancer are associated with advanced age and stage-dependent MET genomic amplification and c-Met overexpression. J Clin Oncol. 2016;34(7):721-730. 4. Nadal E, Chen G, Prensner J, et al. KRAS-G12C mutation is associated with poor outcome in surgically resected lung adenocarcinoma. J Thorac Oncol. 2014;9(10):1513-1522. 5. Scheffler M, Ihle MA, Hein R, et al. K-ras mutation subtypes in NSCLC and associated co-occuring mutations in other oncogenic pathways. J Thorac Oncol. 2019;14(4):606-616. 6. Oxnard GR, Lo PC, Nishino M, et al. Natural history and molecular characteristics of lung cancers harboring EGFR exon 20 insertions. J Thorac Oncol. 2013;8(2):179-184. 7. Arcila ME, Nafa K, Chaft JE, et al. EGFR exon 20 insertion mutations in lung adenocarcinomas: prevalence, molecular heterogeneity, and clinicopathologic characteristics. Mol Cancer Ther. 2013;12(2):220-229. 8. Brustugun OT, Khattak AM, Trømborg AK, et al. BRAF-mutations in non-small cell lung cancer. Lung Cancer. 2014;84(1):36-38. 9. Vaishnavi A, Capelletti M, Le AT, et al. Oncogenic and drug-sensitive NTRK1 rearrangements in lung cancer. Nat Med. 2013;19(11):1469-1472. 10. D’Angelo SP, Pietanza MC, Johnson ML, et al. Incidence of EGFR exon 19 deletions and L858R in tumor specimens from men and cigarette smokers with lung adenocarcinomas. J Clin Oncol. 2011;29(15):2066-2070. 11. Vuong HG, Ho ATN, Altibi AMA, Nakazawa T, Katoh R, Kondo T. Clinicopathological implications of MET exon 14 mutations in non-small cell lung cancer – a systematic review and meta-analysis. Lung Cancer. 2018;123:76-82. 12. Li T, Kung H-J, Mack PC, Gandara DR. Genotyping and genomic profiling of non–small-cell lung cancer: implications for current and future therapies. J Clin Oncol. 2013;31(8):1039-1049. 13. Hirsch FR, Suda K, Wiens J, Bunn PA. New and emerging targeted treatments in advanced non-small-cell lung cancer. Lancet. 2016;388(10048):1012-1024. 14. Lindeman NI, Cagle PT, Aisner DL, et al. Updated Molecular Testing Guideline for the Selection of Lung Cancer Patients for Treatment With Targeted Tyrosine Kinase Inhibitors: Guideline From the College of American Pathologists, the International Association for the Study of Lung Cancer, and the Association for Molecular Pathology. J Mol Diagn. 2018;20(2):129-159. 15. Frampton 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. 16. Pruis MA, Geurts-Giele WRR, von der Thüsen JH, et al. Highly accurate DNA-based detection and treatment results of MET exon 14 skipping mutations in lung cancer. Lung Cancer. 2020;140:46-54. 17. Drilon A. MET exon 14 alterations in lung cancer: exon skipping extends half-life. Clin Cancer Res. 2016;22(12):2832-2834. 18. Smyth EC, Sclafani F, Cunningham D. Emerging molecular targets in oncology: clinical potential of MET/hepatocyte growth-factor inhibitors. Onco Targets Ther. 2014;7:1001-1014. 19. Zhang Y, Xia M, Jin K, et al. Function of the c-Met receptor tyrosine kinase in carcinogenesis and associated therapeutic opportunities. Mol Cancer. 2018;17(1):45. 20. Kim EK, Kim KA, Lee CY, et al. Molecular diagnostic assays and clinicopathologic implications of MET exon 14 skipping mutation in non–small-cell lung cancer. Clin Lung Cancer. 2019;20(1):e123-e132. doi:10.1016/j.cllc.2018.10.004. 21. Hinrichs JW, van Blokland WT, Moons MJ, et al. Comparison of next-generation sequencing and mutation-specific platforms in clinical practice. Am J Clin Pathol. 2015;143(4):573-578. 22. Yu TM, Morrison C, Gold EJ, Tradonsky A, Layton AJ. Multiple biomarker testing tissue consumption and completion rates with single-gene tests and investigational use of Oncomine Dx Target Test for advanced non-small-cell lung cancer: A single-center analysis. Clin Lung Cancer. 2019;20(1):20-29.e1. 23. Pennell NA, Mutebi A, Zhou Z-Y. Economic impact of next-generation sequencing versus single-gene testing to detect genomic alterations in metastatic non–small-cell lung cancer using a decision analytic model. JCO Precis Oncol. 2019. doi:10.1200/PO.18.00356. 24. Drilon A, Wang L, Arcila ME, et al. Broad, hybrid capture–based next-generation sequencing identifies actionable genomic alterations in lung adenocarcinomas otherwise negative for such alterations by other genomic testing approaches. Clin Cancer Res. 2015;21(16):3631-3639. 25. Ali SM, Hensing T, Schrock AB, et al. Comprehensive genomic profiling identifies a subset of crizotinib-responsive ALK-rearranged non-small cell lung cancer not detected by fluorescence in situ hybridization. Oncologist. 2016;21(6):762-770. 26. Foundation Medicine, Inc. FoundationOne®CDx Technical Information. Cambridge, MA: Foundation Medicine, Inc. 27. Foundation Medicine, Inc. FoundationOne®Liquid CDx Technical Information. Cambridge, MA: Foundation Medicine, Inc. 28. Foundation Medicine, Inc. What is FoundationOne CDx? https://www.foundationmedicine.com/test/foundationone-cdx. Accessed June 29, 2021. 29. Foundation Medicine, Inc. Billing and financial assistance. https://www.foundationmedicine.com/resource/billing-and-financial-assistance. Accessed June 29, 2021. 30. Foundation Medicine, Inc. Foundation Medicine mobile phlebotomy. https://assets.ctfassets.net/w98cd481qyp0/4jVqxTjDfcHxzGmzwyKZCb/ec459c0296895b15101ac1a21e066f94/Mobile_Phlebotomy_Overview_HCP.pdf. Accessed June 29, 2021.

 

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Indication

TABRECTA® (capmatinib) tablets is indicated for the treatment of adult patients with metastatic non-small cell lung cancer (NSCLC) whose tumors have a mutation that leads to mesenchymal-epithelial transition (MET) exon 14 skipping as detected by an FDA-approved test.

 

This indication is approved under accelerated approval based on overall response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.


Important Safety Information

Interstitial Lung Disease (ILD)/Pneumonitis. ILD/pneumonitis, which can be fatal, occurred in patients treated with TABRECTA. ILD/pneumonitis occurred in 4.5% of patients treated with TABRECTA in the GEOMETRY mono-1 study, with 1.8% of patients experiencing grade 3 ILD/pneumonitis and 1 patient experiencing death (0.3%). Eight patients (2.4%) discontinued TABRECTA due to ILD/pneumonitis.

 

Monitor for new or worsening pulmonary symptoms indicative of ILD/pneumonitis (eg, dyspnea, cough, fever). Immediately withhold TABRECTA in patients with suspected ILD/pneumonitis and permanently discontinue if no other potential causes of ILD/pneumonitis are identified.

 

Hepatotoxicity. Hepatotoxicity occurred in patients treated with TABRECTA. Increased alanine aminotransferase (ALT)/aspartate aminotransferase (AST) occurred in 13% of patients treated with TABRECTA in GEOMETRY mono-1. Grade 3 or 4 increased ALT/AST occurred in 6% of patients. Three patients (0.9%) discontinued TABRECTA due to increased ALT/AST.

 

Monitor liver function tests (including ALT, AST, and total bilirubin) prior to the start of TABRECTA, every 2 weeks during the first 3 months of treatment, then once a month or as clinically indicated, with more frequent testing in patients who develop increased transaminases or bilirubin. Based on the severity of the adverse reaction, withhold, reduce dose, or permanently discontinue TABRECTA.

 

Risk of Photosensitivity. Based on findings from animal studies, there is a potential risk of photosensitivity reactions with TABRECTA. In GEOMETRY mono-1, it was recommended that patients use precautionary measures against ultraviolet exposure, such as use of sunscreen or protective clothing, during treatment with TABRECTA. Advise patients to limit direct ultraviolet exposure during treatment with TABRECTA.

 

Embryo-Fetal Toxicity. Based on findings from animal studies and its mechanism of action, TABRECTA can cause fetal harm when administered to a pregnant woman. Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with TABRECTA and for 1 week after the last dose. Advise males with female partners of reproductive potential to use effective contraception during treatment with TABRECTA and for 1 week after the last dose.

 

Most Common Adverse Reactions. The most common adverse reactions (≥20%) were peripheral edema (52%), nausea (44%), fatigue (32%), vomiting (28%), dyspnea (24%), and decreased appetite (21%). The most common grade 3 adverse reactions (≥2%) were peripheral edema (9%), fatigue (8%), dyspnea (7%), nausea (2.7%), vomiting (2.4%), and noncardiac chest pain (2.1%). Grade 4 dyspnea was reported in 0.6% of patients.  

 

Clinically Relevant Adverse Reactions. Clinically relevant adverse reactions observed in <10% of patients were pruritus (allergic and generalized), ILD/pneumonitis, cellulitis, acute kidney injury (including renal failure), urticaria, and acute pancreatitis.

 

Laboratory Abnormalities. Select laboratory abnormalities (≥20%) worsening from baseline in patients who received TABRECTA were decreased albumin (68%), increased creatinine (62%), decreased lymphocytes (44%), increased ALT (37%), increased alkaline phosphatase (32%), increased amylase (31%), increased gamma-glutamyltransferase (29%), increased lipase (26%), increased AST (25%), decreased hemoglobin (24%), decreased leukocytes (23%), decreased sodium (23%), decreased phosphate (23%), increased potassium (23%), and decreased glucose (21%).

 

Please see full Prescribing Information for TABRECTA.