{"entity":{"id":"zongertinib","kind":"drug","name":"Zongertinib","aka":[],"tldr":"Zongertinib was the first oral HER2 inhibitor for lung cancer with HER2 mutations, approved in 2025 and moved to first line in 2026.","summary":"Zongertinib is an irreversible HER2-selective tyrosine kinase inhibitor that spares EGFR, which limits the rash and diarrhoea seen with pan-HER inhibitors; it is taken as 120 mg once daily. Beamion LUNG-1 showed a response rate of about 71% in previously treated HER2-mutant NSCLC, leading to accelerated approval in August 2025, and in Q1 2026 it was approved as first-line therapy for HER2-mutant non-squamous NSCLC, the first oral HER2 inhibitor for this setting. Boehringer Ingelheim developed it. Diarrhoea, rash, raised liver enzymes, nausea and fatigue are the main adverse events. It competes with trastuzumab deruxtecan and with sevabertinib (Bayer, approved late 2025), and the best sequence between a pill and an antibody-drug conjugate is unresolved. For a newcomer: the first pill for lung cancers driven by HER2 mutations.","status":"approved","asOf":"2026-09-04","links":[{"label":"FDA label (DailyMed)","url":"https://dailymed.nlm.nih.gov/dailymed/search.cfm?query=Zongertinib"}],"tags":[],"related":["her2-mutation"],"cancers":["nsclc","her2-mutant-nsclc"],"sections":[],"technologies":["kinase-inhibitors"],"targets":["her2"],"drugs":[],"companies":["boehringer-ingelheim"],"institutions":[],"pathways":[],"terms":[],"trials":["nct07195695","nct06324357","nct06581432","nct07486817","nct06151574"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"brand":"Hernexeos","modality":"Small-molecule kinase inhibitor (HER2)","mechanism":"Irreversible HER2-selective TKI sparing EGFR.","approvals":[{"region":"US","year":2025,"indication":"HER2-mutant NSCLC, previously treated (accelerated)"},{"region":"US","year":2026,"indication":"First-line HER2-mutant non-squamous NSCLC"}],"mechanismSteps":["Oral drug is absorbed and reaches the tumour","Binds the ATP pocket (or allosteric site) of mutant HER2 (exon 20 insertions and others)","Phosphorylation of downstream substrates stops","Irreversible, EGFR-sparing binding limits diarrhoea and rash","Oncogene-addicted cells arrest and undergo apoptosis"],"dosing":{"route":"Oral","schedule":"120 mg once daily","modifications":"Reduce for hepatotoxicity, diarrhoea","monitoring":"LFTs, LVEF, respiratory symptoms","source":"https://www.fda.gov/drugs/resources-information-approved-drugs/oncology-cancer-hematologic-malignancies-approval-notifications"},"toxicity":[{"event":"Diarrhoea"},{"event":"Rash"},{"event":"ALT/AST increased"},{"event":"Nausea"},{"event":"Fatigue"}],"access":[{"country":"US","reimbursement":"Medicare Part D (oral); commercial plans per formulary, often with prior authorisation","source":"https://www.cms.gov/medicare/payment/part-b-drugs/asp-pricing-files","asOf":"2026-09-06"}],"regulatoryEvents":[{"date":"2024-03","type":"designation","region":"US","note":"Breakthrough Therapy designation","source":"https://www.fda.gov/drugs/resources-information-approved-drugs/oncology-cancer-hematologic-malignancies-approval-notifications"},{"date":"2025-08-08","type":"accelerated-approval","region":"US","note":"Accelerated approval, previously treated HER2-mutant non-squamous NSCLC (Beamion LUNG-1) The confirmatory requirement was still open 1.1 years later, when the FDA's table was read.","source":"https://www.fda.gov/drugs/resources-information-approved-drugs/oncology-cancer-hematologic-malignancies-approval-notifications","indication":"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 approved test, and who have received prior systemic therapy"},{"date":"2026-Q1","type":"approval","region":"US","note":"First-line HER2-mutant non-squamous NSCLC","source":"https://www.fda.gov/drugs/resources-information-approved-drugs/oncology-cancer-hematologic-malignancies-approval-notifications"},{"date":"2026-02-26","type":"accelerated-approval","region":"US","note":"Accelerated approval on a surrogate endpoint; the confirmatory requirement was still open 0.6 years later, when the FDA's table was read.","source":"https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-zongertinib-unresectable-or-metastatic-non-squamous-non-small-cell","indication":"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"}]},"route":"/drugs/zongertinib/","neighbours":{"biomarker":[{"id":"her2-mutation","kind":"biomarker","name":"HER2 (ERBB2) activating mutation","route":"/biomarkers/her2-mutation/"}],"cancer":[{"id":"her2-mutant-nsclc","kind":"cancer","name":"HER2-mutant non-small-cell lung cancer","route":"/cancers/her2-mutant-nsclc/"},{"id":"lung-cancer","kind":"cancer","name":"Lung cancer (all types)","route":"/cancers/lung-cancer/"},{"id":"nsclc","kind":"cancer","name":"Non-small-cell lung cancer","route":"/cancers/nsclc/"}],"technology":[{"id":"kinase-inhibitors","kind":"technology","name":"Small-molecule kinase inhibitors","route":"/technologies/kinase-inhibitors/"}],"target":[{"id":"her2","kind":"target","name":"HER2","route":"/targets/her2/"}],"company":[{"id":"boehringer-ingelheim","kind":"company","name":"Boehringer Ingelheim","route":"/companies/boehringer-ingelheim/"}],"trial":[{"id":"nct07486817","kind":"trial","name":"Beamion 44: A Study to Test How Well Zongertinib is Tolerated by People With Advanced Non-small Cell Lung Cancer With HER2 Mutations When Given in Combination With Chemotherapy With or Without Pembrolizumab","route":"/trials/nct07486817/"},{"id":"nct06324357","kind":"trial","name":"Beamion BCGC-1: A Study to Find a Suitable Dose of Zongertinib Used Alone and in Combination With Other Treatments to Test Whether it Helps People Wit","route":"/trials/nct06324357/"},{"id":"beamion-lung-1","kind":"trial","name":"Beamion LUNG-1","route":"/trials/beamion-lung-1/"},{"id":"nct06151574","kind":"trial","name":"Beamion LUNG-2: A Study to Test Whether Zongertinib (BI 1810631) Helps People With Advanced Non-small Cell Lung Cancer With HER2 Mutations Compared With Standard Treatment","route":"/trials/nct06151574/"},{"id":"nct07195695","kind":"trial","name":"Beamion LUNG-3: Adjuvant Zongertinib vs Standard Treatment in People With Completely Resected Stage II-IIIB NSCLC Harboring Activating HER2 TKD Mutati","route":"/trials/nct07195695/"},{"id":"nct06581432","kind":"trial","name":"Beamion PANTUMOR-1: A Study to Test Whether Zongertinib Helps People With Advanced Cancers With HER2 Alterations","route":"/trials/nct06581432/"}],"drug":[{"id":"sevabertinib","kind":"drug","name":"Sevabertinib","route":"/drugs/sevabertinib/"}],"paper":[{"id":"paper-beamion-lung-1-zongertinib-nejm-2025","kind":"paper","name":"Beamion LUNG-1: zongertinib in previously treated HER2-mutant non-small-cell lung cancer","route":"/key-papers/paper-beamion-lung-1-zongertinib-nejm-2025/"}],"pathway":[{"id":"nsclc-signalling","kind":"pathway","name":"Non-small cell lung cancer (KEGG map)","route":"/pathways/nsclc-signalling/"},{"id":"rtk-activation","kind":"pathway","name":"Receptor tyrosine kinase activation","route":"/pathways/rtk-activation/"}]}}