{"entity":{"id":"zanidatamab","kind":"drug","name":"Zanidatamab","aka":[],"tldr":"Zanidatamab (Ziihera) is an antibody that grabs HER2 at two different spots, approved for HER2+ bile duct cancer.","summary":"Accelerated approval November 2024 for HER2+ biliary tract cancer (HERIZON-BTC-01). HERIZON-GEA-01 phase 3 in first-line HER2+ gastro-oesophageal cancer with chemotherapy ± tislelizumab was positive (2025). Jazz (ex-Asia) and BeOne. Biparatopic binding drives receptor clustering and internalisation, the basis of the ADC zanidatamab zovodotin.","status":"approved","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/Zanidatamab","links":[{"label":"FDA label (DailyMed)","url":"https://dailymed.nlm.nih.gov/dailymed/search.cfm?query=Zanidatamab"}],"tags":[],"related":["her2-ihc-3-plus"],"cancers":["cholangiocarcinoma","gastric","gallbladder","biliary-tract-cancer"],"sections":[],"technologies":["bispecific-antibody"],"targets":["her2"],"drugs":[],"companies":["jazz","zymeworks","beone"],"institutions":[],"pathways":[],"terms":["her2-testing-in-biliary-cancer"],"trials":["nct06435429","nct07102381","nct06695845"],"people":[],"bottlenecks":[],"keyPapers":["paper-harding-lancet-oncol","paper-angerilli-her2-ihc-cish-biliary-hum-pathol-2026"],"journals":[],"dependsOn":[],"notes":["Gallbladder cancer was the largest anatomical subgroup in HERIZON-BTC-01, which required ERBB2 amplification by central ISH and reported a 41.3% confirmed response rate in the 80 IHC 2+ or 3+ patients (Harding 2023); the FDA label restricts use to IHC 3+ on the Ventana PATHWAY 4B5 assay."],"brand":"Ziihera","modality":"Biparatopic bispecific antibody (HER2)","mechanism":"Binds ECD2 and ECD4 of HER2 simultaneously; clustering, internalisation, ADCC.","approvals":[{"region":"US","year":2024,"indication":"HER2+ (IHC 3+) unresectable/metastatic biliary tract cancer, previously treated","note":"Ziihera label (openFDA); 53% of HERIZON-BTC-01 patients had gallbladder cancer: https://api.fda.gov/drug/label.json?search=openfda.brand_name:%22ZIIHERA%22"},{"region":"EU","year":2025,"indication":"HER2+ biliary tract after ≥1 line; 27 Jun 2025 (conditional)","note":"Conditional marketing authorisation"},{"region":"UK","year":2026,"indication":"HER2-positive (IHC 3+) unresectable locally advanced or metastatic biliary tract cancer after at least one line of systemic treatment; MHRA 19 February 2026, NICE TA1153 published 7 May 2026 with a commercial arrangement","note":"https://www.nice.org.uk/guidance/ta1153"}],"mechanismSteps":["Two arms bind two different HER2 epitopes (ECD2 and ECD4) on one or neighbouring receptors","HER2 receptors cluster and are internalised and degraded","HER2 signalling and dimerisation with HER3 stop","Fc engages immune effectors (ADCC, phagocytosis)","HER2-dependent tumour cells die"],"dosing":{"route":"IV infusion","schedule":"20 mg/kg every 2 weeks","modifications":"Hold for LVEF decline or grade 3 diarrhoea","monitoring":"LVEF at baseline and every 3 months; infusion reactions; diarrhoea","source":"https://www.fda.gov/drugs/resources-information-approved-drugs/oncology-cancer-hematologic-malignancies-approval-notifications"},"toxicity":[{"event":"Diarrhoea"},{"event":"Infusion-related reactions"},{"event":"Abdominal pain"},{"event":"Fatigue"},{"event":"Nausea"},{"event":"Left ventricular dysfunction"}],"access":[{"country":"US","reimbursement":"Medicare Part B (physician-administered); commercial plans per formulary","source":"https://www.cms.gov/medicare/payment/part-b-drugs/asp-pricing-files","asOf":"2026-09-06"}],"regulatoryEvents":[{"date":"2023-01","type":"designation","region":"US","note":"Breakthrough Therapy designation, HER2+ biliary tract cancer","source":"https://www.fda.gov/drugs/resources-information-approved-drugs/oncology-cancer-hematologic-malignancies-approval-notifications"},{"date":"2024-11-20","type":"accelerated-approval","region":"US","note":"Accelerated approval, previously treated HER2+ (IHC3+) biliary tract cancer (HERIZON-BTC-01) The confirmatory requirement was still open 1.8 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 adults with previously treated, unresectable or metastatic HER2-positive (IHC 3+) biliary tract cancer (BTC), as detected by an FDA-approved test"},{"date":"2025-12","type":"filing","region":"US","note":"First-line HER2+ gastro-oesophageal adenocarcinoma (HERIZON-GEA-01) submission","source":"https://www.fda.gov/drugs/resources-information-approved-drugs/oncology-cancer-hematologic-malignancies-approval-notifications"},{"date":"2026-08-25","type":"approval","region":"US","note":"First-line HER2-positive gastric, gastro-oesophageal junction or oesophageal adenocarcinoma with tislelizumab and fluoropyrimidine-platinum chemotherapy","source":"https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-zanidatamab-hrii-and-tislelizumab-jsgr-her2-positive-gastric-gastroesophageal-junction"}]},"route":"/drugs/zanidatamab/","neighbours":{"biomarker":[{"id":"her2-ihc-3-plus","kind":"biomarker","name":"HER2 IHC 3+ (HER2-positive by immunohistochemistry)","route":"/biomarkers/her2-ihc-3-plus/"}],"cancer":[{"id":"biliary-tract-cancer","kind":"cancer","name":"Biliary tract cancer (all types)","route":"/cancers/biliary-tract-cancer/"},{"id":"cholangiocarcinoma","kind":"cancer","name":"Biliary tract cancer (cholangiocarcinoma)","route":"/cancers/cholangiocarcinoma/"},{"id":"her2-positive-early-breast-cancer","kind":"cancer","name":"Early HER2-positive breast cancer","route":"/cancers/her2-positive-early-breast-cancer/"},{"id":"extrahepatic-cholangiocarcinoma","kind":"cancer","name":"Extrahepatic cholangiocarcinoma (perihilar and distal)","route":"/cancers/extrahepatic-cholangiocarcinoma/"},{"id":"gallbladder-adenocarcinoma","kind":"cancer","name":"Gallbladder adenocarcinoma","route":"/cancers/gallbladder-adenocarcinoma/"},{"id":"gallbladder","kind":"cancer","name":"Gallbladder cancer","route":"/cancers/gallbladder/"},{"id":"gastric","kind":"cancer","name":"Gastric & gastro-oesophageal junction cancer","route":"/cancers/gastric/"},{"id":"her2-amplified-colorectal","kind":"cancer","name":"HER2-amplified colorectal cancer","route":"/cancers/her2-amplified-colorectal/"},{"id":"breast-her2-positive","kind":"cancer","name":"HER2-positive breast cancer","route":"/cancers/breast-her2-positive/"},{"id":"her2-positive-breast-brain-metastases","kind":"cancer","name":"HER2-positive breast cancer with brain metastases","route":"/cancers/her2-positive-breast-brain-metastases/"},{"id":"gastric-her2-positive","kind":"cancer","name":"HER2-positive gastric cancer","route":"/cancers/gastric-her2-positive/"},{"id":"intrahepatic-cholangiocarcinoma","kind":"cancer","name":"Intrahepatic cholangiocarcinoma","route":"/cancers/intrahepatic-cholangiocarcinoma/"},{"id":"esophageal","kind":"cancer","name":"Oesophageal cancer","route":"/cancers/esophageal/"}],"technology":[{"id":"bispecific-antibody","kind":"technology","name":"Bispecific antibodies","route":"/technologies/bispecific-antibody/"}],"target":[{"id":"her2","kind":"target","name":"HER2","route":"/targets/her2/"}],"company":[{"id":"beone","kind":"company","name":"BeOne Medicines (formerly BeiGene)","route":"/companies/beone/"},{"id":"jazz","kind":"company","name":"Jazz Pharmaceuticals","route":"/companies/jazz/"},{"id":"zai-lab","kind":"company","name":"Zai Lab","route":"/companies/zai-lab/"},{"id":"zymeworks","kind":"company","name":"Zymeworks","route":"/companies/zymeworks/"}],"term":[{"id":"epitope","kind":"term","name":"Epitope","route":"/terms/epitope/"},{"id":"genomic-testing-biliary-uk","kind":"term","name":"HER2 and genomic testing for biliary cancer on the NHS","route":"/terms/genomic-testing-biliary-uk/"},{"id":"her2-testing-in-biliary-cancer","kind":"term","name":"HER2 testing in biliary tract cancer (IHC, ISH and NGS)","route":"/terms/her2-testing-in-biliary-cancer/"}],"trial":[{"id":"nct07102381","kind":"trial","name":"A Phase 2 Neoadjuvant Study of Zanidatamab in Combination With Chemotherapy in Participants With HER2-positive Breast Cancer","route":"/trials/nct07102381/"},{"id":"nct06695845","kind":"trial","name":"A Phase 2 Study of Zanidatamab in Patients With HER2-expressing Tumors","route":"/trials/nct06695845/"},{"id":"nct06435429","kind":"trial","name":"A Study Comparing the Efficacy and Safety of Zanidatamab to Trastuzumab, Each in Combination With Physician's Choice Chemotherapy, for the Treatment o","route":"/trials/nct06435429/"},{"id":"nct07631871","kind":"trial","name":"An Exploratory Study of Zanidatamab in HER2-positive Advanced Tumor After at Least One Line of Standard Therapy","route":"/trials/nct07631871/"},{"id":"nct07192068","kind":"trial","name":"Clinical Trial Evaluating the Activity of Zanidatamab for the Treatment of Patients With Solid Tumors With an Alteration of the HER2 Gene.","route":"/trials/nct07192068/"},{"id":"herizon-btc-01","kind":"trial","name":"HERIZON-BTC-01","route":"/trials/herizon-btc-01/"},{"id":"herizon-btc-302","kind":"trial","name":"HERIZON-BTC-302","route":"/trials/herizon-btc-302/"},{"id":"herizon-gea-01","kind":"trial","name":"HERIZON-GEA-01","route":"/trials/herizon-gea-01/"},{"id":"nct07745296","kind":"trial","name":"Investigating Precision Medicine in the Adjuvant Setting in Biliary Tract Cancer","route":"/trials/nct07745296/"},{"id":"nct07243938","kind":"trial","name":"Phase II Basket Trial: Zanidatamab Plus Tislelizumab in HER2-Positive GI Tumors (UNION-HER2-BASKET)","route":"/trials/nct07243938/"},{"id":"nct05868226","kind":"trial","name":"PRE-ISPY Phase I/II Oncology Platform Program","route":"/trials/nct05868226/"},{"id":"safir-abc10","kind":"trial","name":"SAFIR-ABC10","route":"/trials/safir-abc10/"},{"id":"nct07405476","kind":"trial","name":"Zanidatamab Before Surgery for the Treatment of HER2 Positive Colon and Rectal Cancer in Patients Planned for Curative Intent Treatment","route":"/trials/nct07405476/"}],"paper":[{"id":"paper-mondaca-erbb2-gallbladder-us-chile-jco-go-2024","kind":"paper","name":"Clinical and genomic characterization of ERBB2-altered gallbladder cancer: exploring differences between an American and a Chilean cohort","route":"/key-papers/paper-mondaca-erbb2-gallbladder-us-chile-jco-go-2024/"},{"id":"paper-angerilli-her2-ihc-cish-biliary-hum-pathol-2026","kind":"paper","name":"HER2 status in extrahepatic cholangiocarcinoma and gallbladder carcinoma: concordance between immunohistochemistry and chromogenic in situ hybridization in 140 cases","route":"/key-papers/paper-angerilli-her2-ihc-cish-biliary-hum-pathol-2026/"},{"id":"paper-harding-lancet-oncol","kind":"paper","name":"Zanidatamab for HER2-amplified, unresectable, locally advanced or metastatic biliary tract cancer (HERIZON-BTC-01): a multicentre, single-arm, phase 2b study","route":"/key-papers/paper-harding-lancet-oncol/"}],"pairing":[{"id":"her2-gastric-sequence","kind":"pairing","name":"HER2 sequence in gastric cancer: zanidatamab/trastuzumab + chemo ± PD-1 → T-DXd","route":"/pairings/her2-gastric-sequence/"}],"idea":[{"id":"idea-biomarker-quadruplet-gastric","kind":"idea","name":"Biomarker-directed first-line quadruplets in gastric cancer","route":"/ideas/idea-biomarker-quadruplet-gastric/"},{"id":"idea-gbc-reflex-her2-testing-advanced-biliary","kind":"idea","name":"Reflex HER2 testing of every advanced gallbladder and extrahepatic biliary cancer","route":"/ideas/idea-gbc-reflex-her2-testing-advanced-biliary/"}],"roadmap":[{"id":"gallbladder-cancer-roadmap","kind":"roadmap","name":"Gallbladder cancer roadmap: from a chance finding at gallstone surgery to a disease with its own trials","route":"/roadmaps/gallbladder-cancer-roadmap/"}],"person":[{"id":"lee-jeeyun","kind":"person","name":"Jeeyun Lee","route":"/people/lee-jeeyun/"}],"pathway":[{"id":"gastric-cancer-signalling","kind":"pathway","name":"Gastric cancer (KEGG map)","route":"/pathways/gastric-cancer-signalling/"},{"id":"rtk-activation","kind":"pathway","name":"Receptor tyrosine kinase activation","route":"/pathways/rtk-activation/"}],"drug":[{"id":"zanidatamab-zovodotin","kind":"drug","name":"Zanidatamab zovodotin","route":"/drugs/zanidatamab-zovodotin/"}]}}