{"entity":{"id":"herizon-btc-01","kind":"trial","name":"HERIZON-BTC-01","aka":[],"tldr":"The trial behind the first HER2 drug approved for bile duct and gallbladder cancer: zanidatamab shrank tumours in 41 percent of 80 people with HER2-positive disease that had progressed on chemotherapy, and more than half of those enrolled had gallbladder cancer. It led to approvals in the United States, the European Union and the UK, where NICE recommended it in May 2026.","summary":"HERIZON-BTC-01 (NCT04466891) is a global, multicentre, single-arm phase 2b at 32 sites in nine countries, including three London hospitals (University College London Hospitals, the Royal Free and Imperial). Between September 2020 and March 2022 it enrolled 87 patients with HER2-amplified biliary tract cancer confirmed by central in-situ hybridisation after progression on gemcitabine-based therapy: 80 in cohort 1 (HER2 IHC 2+ or 3+) and 7 in cohort 2 (IHC 0 or 1+). By the FDA label, 53 percent had gallbladder cancer, 27 percent intrahepatic and 19 percent extrahepatic cholangiocarcinoma, making it the trial with the largest gallbladder share of any approval study in the field. Confirmed objective response by independent central review in cohort 1, the primary endpoint, was 41.3 percent (33 of 80; 95 percent confidence interval 30.4 to 52.8) at a median follow-up of 12.4 months; 18 percent had grade 3 treatment-related adverse events (diarrhoea 5 percent, reduced ejection fraction 3 percent), with no grade 4 events or treatment-related deaths. Final results appeared in JAMA Oncology in 2026 and a post-hoc analysis reported survival by HER2 expression. The FDA granted accelerated approval in November 2024 for previously treated HER2-positive (IHC 3+) biliary tract cancer, the European Commission conditional approval on 27 June 2025, the MHRA approval on 19 February 2026, and NICE TA1153 (7 May 2026) recommends it for HER2-positive (IHC 3+) unresectable or metastatic biliary tract cancer after at least one line of systemic treatment, with FOLFOX or active symptom control as the comparators the committee considered. The randomised first-line HERIZON-BTC-302 trial is the confirmatory study.","status":"positive","asOf":"2026-09-24","links":[{"label":"ClinicalTrials.gov NCT04466891","url":"https://clinicaltrials.gov/study/NCT04466891"},{"label":"Harding et al., Lancet Oncology 2023: HERIZON-BTC-01","url":"https://doi.org/10.1016/S1470-2045(23)00242-5"},{"label":"Final results from HERIZON-BTC-01, JAMA Oncology 2026","url":"https://doi.org/10.1001/jamaoncol.2025.4736"},{"label":"Ziihera label (openFDA)","url":"https://api.fda.gov/drug/label.json?search=openfda.brand_name:%22ZIIHERA%22"},{"label":"NICE TA1153: zanidatamab for HER2-positive advanced biliary tract cancer (7 May 2026)","url":"https://www.nice.org.uk/guidance/ta1153"}],"tags":[],"related":["herizon-btc-302"],"cancers":["gallbladder","cholangiocarcinoma","intrahepatic-cholangiocarcinoma","extrahepatic-cholangiocarcinoma","biliary-tract-cancer"],"sections":[],"technologies":["bispecific-antibody"],"targets":["her2"],"drugs":["zanidatamab"],"companies":["jazz","zymeworks","beone"],"institutions":["uclh"],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-harding-lancet-oncol","paper-angerilli-her2-gallbladder-extrahepatic-concordance-hum-pathol-2026"],"journals":[],"dependsOn":[],"notes":["Key figures: 87 enrolled at 32 sites in nine countries (80 in cohort 1, HER2 IHC 2+ or 3+); confirmed response by independent central review 41.3 percent (33 of 80; 30.4 to 52.8) at a median follow-up of 12.4 months; grade 3 treatment-related adverse events 18 percent (diarrhoea 5, reduced ejection fraction 3), no grade 4 or treatment-related deaths. Approvals: FDA accelerated November 2024 (IHC 3+), European Commission conditional 27 June 2025, MHRA 19 February 2026, NICE TA1153 7 May 2026 (HER2 IHC 3+, after at least one line, commercial arrangement; FOLFOX or active symptom control as comparators).","UK sites (3, registry): University College London Hospitals, Royal Free London, Imperial College Healthcare (all London).","Tumour type split from the Ziihera label: gallbladder cancer 53%, intrahepatic cholangiocarcinoma 27%, extrahepatic cholangiocarcinoma 19%."],"nct":"NCT04466891","phase":"2","setting":"HER2-amplified unresectable, locally advanced or metastatic biliary tract cancer after gemcitabine-based therapy: zanidatamab 20 mg/kg every 2 weeks, single arm; cohort 1 IHC 2+ or 3+ (n=80), cohort 2 IHC 0 or 1+ (n=7)","sponsor":"Jazz Pharmaceuticals (Zymeworks, BeOne)","result":"Confirmed ORR by independent central review 41.3% (33/80, 95% CI 30.4 to 52.8) in HER2 IHC 2+/3+ cohort; grade 3 treatment-related adverse events 18%; 53% of patients had gallbladder cancer.","yearReported":2023,"enrolled":87,"enrolledBasis":"registry","outcomes":[{"endpoint":"Grade 3 treatment-related adverse events","unit":"%","arms":[{"name":"Zanidatamab","n":87,"value":18}],"source":"https://doi.org/10.1016/S1470-2045(23)00242-5"}]},"route":"/trials/herizon-btc-01/","neighbours":{"trial":[{"id":"herizon-btc-302","kind":"trial","name":"HERIZON-BTC-302","route":"/trials/herizon-btc-302/"}],"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":"extrahepatic-cholangiocarcinoma","kind":"cancer","name":"Extrahepatic cholangiocarcinoma (perihilar and distal)","route":"/cancers/extrahepatic-cholangiocarcinoma/"},{"id":"gallbladder","kind":"cancer","name":"Gallbladder cancer","route":"/cancers/gallbladder/"},{"id":"intrahepatic-cholangiocarcinoma","kind":"cancer","name":"Intrahepatic cholangiocarcinoma","route":"/cancers/intrahepatic-cholangiocarcinoma/"}],"technology":[{"id":"bispecific-antibody","kind":"technology","name":"Bispecific antibodies","route":"/technologies/bispecific-antibody/"}],"target":[{"id":"her2","kind":"target","name":"HER2","route":"/targets/her2/"}],"drug":[{"id":"zanidatamab","kind":"drug","name":"Zanidatamab","route":"/drugs/zanidatamab/"}],"company":[{"id":"beone","kind":"company","name":"BeOne Medicines (formerly BeiGene)","route":"/companies/beone/"},{"id":"jazz","kind":"company","name":"Jazz Pharmaceuticals","route":"/companies/jazz/"},{"id":"zymeworks","kind":"company","name":"Zymeworks","route":"/companies/zymeworks/"}],"institution":[{"id":"uclh","kind":"institution","name":"University College London Hospitals / UCL Cancer Institute","route":"/institutions/uclh/"}],"paper":[{"id":"paper-angerilli-her2-gallbladder-extrahepatic-concordance-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-gallbladder-extrahepatic-concordance-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/"}],"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/"}],"idea":[{"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/"}],"term":[{"id":"gallbladder-cancer-in-biliary-trials","kind":"term","name":"Gallbladder cancer in biliary tract cancer trials (eligibility and subgroups)","route":"/terms/gallbladder-cancer-in-biliary-trials/"}]}}