{"entity":{"id":"egfr-exon-20-insertion","kind":"biomarker","name":"EGFR exon 20 insertion","aka":["EGFR ex20ins","exon 20 insertion","EGFR exon 20 insertion mutation","EGFR ex20ins NSCLC"],"tldr":"Exon 20 insertions add amino acids after the C-helix of EGFR and make the kinase resistant to the usual EGFR tablets. They account for about a tenth of EGFR mutations and have their own drugs: amivantamab with chemotherapy and sunvozertinib.","summary":"In-frame insertions or duplications in exon 20 (A767_V769dup, D770_N771insSVD and others) are structurally distinct from the classical mutations and do not respond to first- or third-generation TKIs at tolerated doses. Amivantamab is labelled with carboplatin and pemetrexed for first-line NSCLC with EGFR exon 20 insertion mutations (PAPILLON) and alone after platinum chemotherapy; sunvozertinib (Zegfrovy, 2025) is labelled after platinum chemotherapy with the Oncomine Dx Express Test as companion; mobocertinib was withdrawn in 2023. Guardant360 CDx and the Oncomine Dx Target Test carry exon 20 insertion claims for amivantamab. PCR hotspot kits miss many exon 20 insertions, so sequencing is preferred.","asOf":"2026-09-23","links":[{"label":"Rybrevant prescribing information (DailyMed)","url":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=1466c070-9f97-4fa4-a955-6a6b59981fb8"}],"tags":["biomarker","egfr"],"related":["egfr-exon-19-deletion","her2-mutation"],"cancers":["nsclc"],"sections":[],"technologies":[],"targets":[],"drugs":["amivantamab","sunvozertinib","mobocertinib","zipalertinib","guardant360-cdx","oncomine-dx-target-test"],"companies":[],"institutions":[],"pathways":[],"terms":["egfr-exon20-insertion","egfr-mutation-subtypes","ngs"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"target":"egfr","measurement":"sequencing-variant","scoringRule":{"text":"An in-frame insertion or duplication within exon 20 of EGFR (excluding T790M) detected by next-generation sequencing of tumour tissue or plasma.","quote":"Exon 20 insertion mutations","source":"https://www.fda.gov/medical-devices/in-vitro-diagnostics/list-cleared-or-approved-companion-diagnostic-devices-in-vitro-and-imaging-tools","sourceLabel":"FDA: List of FDA-Authorized Companion Diagnostic Devices"},"thresholds":[{"value":"EGFR exon 20 insertion","drugId":"amivantamab","cancerId":"nsclc","regulator":"FDA","source":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=1466c070-9f97-4fa4-a955-6a6b59981fb8","status":"current","note":"Rybrevant indications 1.2 and 1.3: with carboplatin and pemetrexed for first-line, and as a single agent after platinum chemotherapy, in NSCLC with EGFR exon 20 insertion mutations as detected by an FDA-approved test."}],"tests":["foundationone-cdx","guardant360-cdx","tempus-xt","trusight-oncology-comprehensive"],"assays":["oncomine-dx","guardant360-cdx"],"companionDiagnostics":[{"device":"Guardant360 CDx","maker":"Guardant Health","companyId":"guardant-health","drugs":["amivantamab"],"indication":"Non-Small Cell Lung Cancer (NSCLC) - Plasma","pma":"P200010/S001 (05/21/2021)","source":"https://www.fda.gov/medical-devices/in-vitro-diagnostics/list-cleared-or-approved-companion-diagnostic-devices-in-vitro-and-imaging-tools"},{"device":"Oncomine Dx Target Test","maker":"Life Technologies (Thermo Fisher Scientific)","companyId":"thermo-fisher","drugs":["amivantamab"],"indication":"Non-Small Cell Lung Cancer (NSCLC) - Tissue","pma":"P160045/S027 (12/01/2021)","source":"https://www.fda.gov/medical-devices/in-vitro-diagnostics/list-cleared-or-approved-companion-diagnostic-devices-in-vitro-and-imaging-tools"},{"device":"Oncomine Dx Express Test","maker":"Life Technologies (Thermo Fisher Scientific)","companyId":"thermo-fisher","drugs":["sunvozertinib"],"indication":"Non-Small Cell Lung Cancer (NSCLC) - Tissue","pma":"P240040 (07/02/2025)","source":"https://www.fda.gov/medical-devices/in-vitro-diagnostics/list-cleared-or-approved-companion-diagnostic-devices-in-vitro-and-imaging-tools"}],"forPatient":"An exon 20 insertion is an EGFR mutation that the common EGFR tablets do not treat well. The on-label first treatment is amivantamab with chemotherapy; after chemotherapy, amivantamab alone or sunvozertinib. Make sure the mutation was found by sequencing, because older hotspot tests can miss it."},"route":"/biomarkers/egfr-exon-20-insertion/","neighbours":{"biomarker":[{"id":"egfr-exon-19-deletion","kind":"biomarker","name":"EGFR exon 19 deletion","route":"/biomarkers/egfr-exon-19-deletion/"},{"id":"her2-mutation","kind":"biomarker","name":"HER2 (ERBB2) activating mutation","route":"/biomarkers/her2-mutation/"}],"cancer":[{"id":"nsclc","kind":"cancer","name":"Non-small-cell lung cancer","route":"/cancers/nsclc/"}],"drug":[{"id":"amivantamab","kind":"drug","name":"Amivantamab","route":"/drugs/amivantamab/"},{"id":"guardant360-cdx","kind":"drug","name":"Guardant360 CDx","route":"/drugs/guardant360-cdx/"},{"id":"mobocertinib","kind":"drug","name":"Mobocertinib","route":"/drugs/mobocertinib/"},{"id":"oncomine-dx-target-test","kind":"drug","name":"Oncomine Dx Target Test","route":"/drugs/oncomine-dx-target-test/"},{"id":"sunvozertinib","kind":"drug","name":"Sunvozertinib","route":"/drugs/sunvozertinib/"},{"id":"zipalertinib","kind":"drug","name":"Zipalertinib","route":"/drugs/zipalertinib/"}],"term":[{"id":"egfr-exon20-insertion","kind":"term","name":"EGFR exon 20 insertion","route":"/terms/egfr-exon20-insertion/"},{"id":"egfr-mutation-subtypes","kind":"term","name":"EGFR mutation subtypes (exon 19 deletion, L858R, exon 20 insertion, T790M)","route":"/terms/egfr-mutation-subtypes/"},{"id":"ngs","kind":"term","name":"Next-generation sequencing (NGS)","route":"/terms/ngs/"}],"target":[{"id":"egfr","kind":"target","name":"EGFR","route":"/targets/egfr/"}]}}