{"entity":{"id":"her2-mutation","kind":"biomarker","name":"HER2 (ERBB2) activating mutation","aka":["HER2 mutation","ERBB2 mutation","HER2-mutant NSCLC","ERBB2 exon 20 insertion","HER2 tyrosine kinase domain mutation","HER2 YVMA insertion","HER2 TKD mutation"],"tldr":"A HER2 mutation is a change in the gene's kinase domain, most often an exon 20 insertion, found in about 2 to 3 percent of lung adenocarcinomas. It is a different thing from HER2 amplification or overexpression, and it selects trastuzumab deruxtecan and, since 2025, zongertinib in lung cancer.","summary":"Activating ERBB2 mutations cluster in the tyrosine kinase domain (exons 18 to 21), the commonest being the exon 20 insertion A775_G776insYVMA; they are detected by sequencing of tumour tissue or plasma. Trastuzumab deruxtecan's label covers unresectable or metastatic NSCLC whose tumours have activating HER2 (ERBB2) mutations in tumour or plasma specimens after prior systemic therapy (DESTINY-Lung02). Zongertinib (Hernexeos), approved in 2025, is labelled for non-squamous NSCLC with HER2 (ERBB2) tyrosine kinase domain activating mutations detected by an FDA-authorised test, testing plasma first and tissue if plasma is negative. The FDA list carries the Oncomine Dx Target Test and Guardant360 CDx for both drugs.","asOf":"2026-09-23","links":[{"label":"ENHERTU prescribing information (DailyMed)","url":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=7e67e73e-ddf4-4e4d-8b50-09d7514910b6"},{"label":"HERNEXEOS prescribing information (DailyMed)","url":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=d3fabf12-354e-4e5c-b5de-20fdb579b783"}],"tags":["biomarker","her2"],"related":["her2-ihc-3-plus","her2-ish-amplified","egfr-exon-20-insertion"],"cancers":["nsclc"],"sections":[],"technologies":[],"targets":[],"drugs":["trastuzumab-deruxtecan","zongertinib","oncomine-dx-target-test","guardant360-cdx"],"companies":[],"institutions":[],"pathways":[],"terms":["ngs","egfr-exon20-insertion"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"target":"her2","measurement":"sequencing-variant","scoringRule":{"text":"Presence of an activating ERBB2 mutation (single nucleotide variants in exons 18 to 21 of the tyrosine kinase domain or exon 20 insertions) by sequencing of tumour tissue or plasma; a negative plasma result should be followed by tissue testing.","quote":"ERBB2/HER2 activating mutations (SNVs in exons 18-21 within the tyrosine kinase domain and exon 20 insertions)","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":"Activating HER2 (ERBB2) mutation, tumour or plasma","drugId":"trastuzumab-deruxtecan","cancerId":"nsclc","regulator":"FDA","source":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=7e67e73e-ddf4-4e4d-8b50-09d7514910b6","quote":"Select patients for the treatment of unresectable or metastatic HER2-mutant NSCLC with ENHERTU based on the presence of activating HER2 (ERBB2) mutations in tumor or plasma specimens","status":"current"},{"value":"HER2 (ERBB2) tyrosine kinase domain activating mutation","drugId":"zongertinib","cancerId":"nsclc","regulator":"FDA","source":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=d3fabf12-354e-4e5c-b5de-20fdb579b783","quote":"HERNEXEOS is indicated for the treatment of adult patients with unresectable or metastatic non-squamous non-small cell lung cancer (NSCLC) whose tumors have HER2 (ERBB2) tyrosine kinase domain activating mutations, as detected by an FDA-authorized test","status":"current"}],"tests":["foundationone-cdx","guardant360-cdx","tempus-xt","trusight-oncology-comprehensive"],"assays":["oncomine-dx","guardant360-cdx"],"companionDiagnostics":[{"device":"Oncomine Dx Target Test","maker":"Life Technologies (Thermo Fisher Scientific)","companyId":"thermo-fisher","drugs":["trastuzumab-deruxtecan"],"indication":"Non-Small Cell Lung Cancer (NSCLC) - Tissue","pma":"P160045/S035 (08/11/2022)","source":"https://www.fda.gov/medical-devices/in-vitro-diagnostics/list-cleared-or-approved-companion-diagnostic-devices-in-vitro-and-imaging-tools"},{"device":"Guardant360 CDx","maker":"Guardant Health","companyId":"guardant-health","drugs":["trastuzumab-deruxtecan"],"indication":"Non-Small Cell Lung Cancer (NSCLC) - Plasma","pma":"P200010/S008 (08/11/2022)","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":["zongertinib"],"indication":"Non-Small Cell Lung cancer (NSCLC) - Tissue","pma":"P160045/S049 (08/08/2025)","source":"https://www.fda.gov/medical-devices/in-vitro-diagnostics/list-cleared-or-approved-companion-diagnostic-devices-in-vitro-and-imaging-tools"},{"device":"Guardant360 CDx","maker":"Guardant Health","companyId":"guardant-health","drugs":["zongertinib"],"indication":"Non-small cell lung cancer (NSCLC) - Plasma","pma":"P200010/S027 (06/10/2026)","source":"https://www.fda.gov/medical-devices/in-vitro-diagnostics/list-cleared-or-approved-companion-diagnostic-devices-in-vitro-and-imaging-tools"}],"forPatient":"A HER2 mutation in lung cancer is found by a gene sequencing test, not by the HER2 stain used in breast cancer. If your report shows one, zongertinib is an on-label first treatment and trastuzumab deruxtecan is on label after prior treatment. If only a blood test was done and it was negative, the label asks for the tumour tissue to be tested too."},"route":"/biomarkers/her2-mutation/","neighbours":{"biomarker":[{"id":"egfr-exon-20-insertion","kind":"biomarker","name":"EGFR exon 20 insertion","route":"/biomarkers/egfr-exon-20-insertion/"},{"id":"her2-ihc-3-plus","kind":"biomarker","name":"HER2 IHC 3+ (HER2-positive by immunohistochemistry)","route":"/biomarkers/her2-ihc-3-plus/"},{"id":"her2-ish-amplified","kind":"biomarker","name":"HER2 ISH amplified (ERBB2 gene amplification)","route":"/biomarkers/her2-ish-amplified/"}],"cancer":[{"id":"nsclc","kind":"cancer","name":"Non-small-cell lung cancer","route":"/cancers/nsclc/"}],"drug":[{"id":"guardant360-cdx","kind":"drug","name":"Guardant360 CDx","route":"/drugs/guardant360-cdx/"},{"id":"oncomine-dx-target-test","kind":"drug","name":"Oncomine Dx Target Test","route":"/drugs/oncomine-dx-target-test/"},{"id":"trastuzumab-deruxtecan","kind":"drug","name":"Trastuzumab deruxtecan","route":"/drugs/trastuzumab-deruxtecan/"},{"id":"zongertinib","kind":"drug","name":"Zongertinib","route":"/drugs/zongertinib/"}],"term":[{"id":"egfr-exon20-insertion","kind":"term","name":"EGFR exon 20 insertion","route":"/terms/egfr-exon20-insertion/"},{"id":"ngs","kind":"term","name":"Next-generation sequencing (NGS)","route":"/terms/ngs/"}],"target":[{"id":"her2","kind":"target","name":"HER2","route":"/targets/her2/"}]}}