{"entity":{"id":"met-amplification-readout","kind":"biomarker","name":"MET amplification (gene copy number)","aka":["MET amplification","MET amp","MET copy number gain","MET/CEP7 ratio","high-level MET amplification","MET GCN >= 10"],"tldr":"MET amplification means extra copies of the MET gene, either as a primary driver in a few lung cancers or as the escape route after EGFR inhibitors. No label yet selects on it; trials define it by FISH ratio or copy number.","summary":"MET amplification is scored by FISH as MET/CEP7 ratio (high-level at 5 or more in the Camidge classification, or 2 or more with mean copies of 10 or more) or by sequencing as gene copy number (GCN 10 or more is the common trial threshold). It occurs de novo in 1 to 4 percent of NSCLC and arises in 5 to 20 percent of EGFR-mutant cancers progressing on osimertinib, the setting of the MARIPOSA-2 and the SAVANNAH trial of osimertinib plus savolitinib (NCT03778229). No approval names MET amplification as the selection criterion; amivantamab is approved on EGFR status rather than MET, and capmatinib's label covers exon 14 skipping only.","asOf":"2026-09-23","links":[{"label":"SAVANNAH (NCT03778229)","url":"https://clinicaltrials.gov/study/NCT03778229"}],"tags":["biomarker","met","no-approval"],"related":["met-ex14","met-overexpression","egfr-t790m"],"cancers":["nsclc","gastric"],"sections":[],"technologies":[],"targets":[],"drugs":["capmatinib","tepotinib","amivantamab","telisotuzumab-vedotin"],"companies":[],"institutions":[],"pathways":[],"terms":["met-amplification","gene-amplification","fish"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-engelman-met-amplification-gefitinib-resistance-science-2007","paper-yu-acquired-resistance-rebiopsy-egfr-ccr-2013","paper-awad-met-exon-14-mutations-lung-jco-2016"],"journals":[],"dependsOn":[],"notes":["Lung cancer: 2 to 3% at diagnosis (cBioPortal) and commoner as acquired resistance, in 4 of 18 specimens resistant to a first-generation EGFR inhibitor (Engelman 2007) and 4 of 75 in the larger rebiopsy series (Yu 2013). There is no agreed copy-number threshold, which is the practical problem: low-level gain accompanies the aneuploidy of a third of lung tumours, and the ratio to chromosome 7 rather than the absolute copy number is what separates focal amplification from polysomy. When it is the resistance mechanism, the EGFR inhibitor should be continued and a MET inhibitor added rather than substituted."],"target":"met","measurement":"copy-number","scoringRule":{"text":"MET/CEP7 ratio by FISH (high-level 5 or more) or MET gene copy number by sequencing (trial thresholds of 6 or 10 copies); no label defines a threshold.","quote":"MET amplification (bypass resistance)","source":"https://clinicaltrials.gov/study/NCT03778229","sourceLabel":"SAVANNAH trial (NCT03778229): MET overexpression and/or amplification defined by IHC 90 percent 3+ or FISH 10 or more copies"},"thresholds":[],"definedBy":{"label":"SAVANNAH: osimertinib plus savolitinib in MET-amplified or overexpressed EGFR-mutant NSCLC after osimertinib (ClinicalTrials.gov NCT03778229)","url":"https://clinicaltrials.gov/study/NCT03778229"},"tests":["foundationone-cdx","foundationone-liquid-cdx","guardant360-cdx","tempus-xt","caris-mi-profile"],"assays":[],"companionDiagnostics":[],"forPatient":"MET amplification on your report does not yet open an approved treatment on its own. If your lung cancer is EGFR-mutant and grew on osimertinib, it is the reason trials combine a MET inhibitor with the EGFR drug, and your team may discuss those trials or amivantamab, which is approved on EGFR status."},"route":"/biomarkers/met-amplification-readout/","neighbours":{"biomarker":[{"id":"met-overexpression","kind":"biomarker","name":"c-Met protein overexpression (IHC 3+ in >= 50% of tumour cells)","route":"/biomarkers/met-overexpression/"},{"id":"egfr-t790m","kind":"biomarker","name":"EGFR T790M","route":"/biomarkers/egfr-t790m/"},{"id":"met-ex14","kind":"biomarker","name":"MET exon 14 skipping mutation","route":"/biomarkers/met-ex14/"}],"cancer":[{"id":"gastric","kind":"cancer","name":"Gastric & gastro-oesophageal junction cancer","route":"/cancers/gastric/"},{"id":"nsclc","kind":"cancer","name":"Non-small-cell lung cancer","route":"/cancers/nsclc/"}],"drug":[{"id":"amivantamab","kind":"drug","name":"Amivantamab","route":"/drugs/amivantamab/"},{"id":"capmatinib","kind":"drug","name":"Capmatinib","route":"/drugs/capmatinib/"},{"id":"telisotuzumab-vedotin","kind":"drug","name":"Telisotuzumab vedotin","route":"/drugs/telisotuzumab-vedotin/"},{"id":"tepotinib","kind":"drug","name":"Tepotinib","route":"/drugs/tepotinib/"}],"term":[{"id":"fish","kind":"term","name":"FISH / ISH (in situ hybridisation)","route":"/terms/fish/"},{"id":"gene-amplification","kind":"term","name":"Gene amplification and copy-number change","route":"/terms/gene-amplification/"},{"id":"met-amplification","kind":"term","name":"MET amplification (bypass resistance)","route":"/terms/met-amplification/"}],"paper":[{"id":"paper-yu-acquired-resistance-rebiopsy-egfr-ccr-2013","kind":"paper","name":"Analysis of tumor specimens at the time of acquired resistance to EGFR-TKI therapy in 155 patients with EGFR-mutant lung cancers","route":"/key-papers/paper-yu-acquired-resistance-rebiopsy-egfr-ccr-2013/"},{"id":"paper-sequist-genotypic-histological-evolution-egfr-resistance-sci-transl-med-2011","kind":"paper","name":"Genotypic and histological evolution of lung cancers acquiring resistance to EGFR inhibitors","route":"/key-papers/paper-sequist-genotypic-histological-evolution-egfr-resistance-sci-transl-med-2011/"},{"id":"paper-engelman-met-amplification-gefitinib-resistance-science-2007","kind":"paper","name":"MET amplification leads to gefitinib resistance in lung cancer by activating ERBB3 signaling","route":"/key-papers/paper-engelman-met-amplification-gefitinib-resistance-science-2007/"},{"id":"paper-awad-met-exon-14-mutations-lung-jco-2016","kind":"paper","name":"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","route":"/key-papers/paper-awad-met-exon-14-mutations-lung-jco-2016/"}],"target":[{"id":"met","kind":"target","name":"MET","route":"/targets/met/"}]}}