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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.
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.
Numbers are from the trial as recorded here; see the source links in the table below. This is orientation, not medical advice: ask your team how closely the trial population matches you.
A direct check of the HERIZON-BTC-01 testing algorithm in routine pathology: IHC 3+ can stand alone, 2+ needs ISH, and the low-level amplification in weakly stained tumours is the group where HER2 drugs are least likely to help.
One cancer page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.
Shares University College London Hospitals / UCL Cancer Institute, Extrahepatic cholangiocarcinoma (perihilar and distal), Intrahepatic cholangiocarcinoma, Gallbladder cancer in biliary tract cancer trials (eligibility and subgroups).
Shares Extrahepatic cholangiocarcinoma (perihilar and distal), Intrahepatic cholangiocarcinoma, Gallbladder cancer in biliary tract cancer trials (eligibility and subgroups), Bispecific antibodies.
Shares Extrahepatic cholangiocarcinoma (perihilar and distal), Intrahepatic cholangiocarcinoma, Gallbladder cancer in biliary tract cancer trials (eligibility and subgroups), Biliary tract cancer (all types).
Shares Extrahepatic cholangiocarcinoma (perihilar and distal), Intrahepatic cholangiocarcinoma, Gallbladder cancer in biliary tract cancer trials (eligibility and subgroups), Biliary tract cancer (all types).
Shares Zanidatamab, Extrahepatic cholangiocarcinoma (perihilar and distal), Intrahepatic cholangiocarcinoma, Gallbladder cancer in biliary tract cancer trials (eligibility and subgroups).
Shares Extrahepatic cholangiocarcinoma (perihilar and distal), Intrahepatic cholangiocarcinoma, Gallbladder cancer in biliary tract cancer trials (eligibility and subgroups), Biliary tract cancer (all types).
Shares Extrahepatic cholangiocarcinoma (perihilar and distal), Intrahepatic cholangiocarcinoma, Gallbladder cancer in biliary tract cancer trials (eligibility and subgroups), Biliary tract cancer (all types).
Shares Extrahepatic cholangiocarcinoma (perihilar and distal), Intrahepatic cholangiocarcinoma, Gallbladder cancer in biliary tract cancer trials (eligibility and subgroups), Biliary tract cancer (all types).