Pivotal Study of Zanidatamab for HER2-Expressing Biliary Tract Cancer Now Fully Enrolled


The phase 2 HERIZON-BTC-01 of zanidatamab in patients with HER2-amplified biliary tract cancer has met its patient enrollment goal.

The final patient with a previously treated advanced or metastatic HER2-amplified biliary tract cancer (BTC) has been enrolled in the global HERIZON-BTC-01 pivotal clinical trial, which is assessing treatment single-agent zanidatamab (ZW25), according to a press release by Zymeworks, Inc.1

HERIZON-BTC-01 is a global, multicenter, open-label, single-arm study (NCT04466891) that includes patients with gallbladder cancer and cholangiocarcinoma, 2 rare adult cancers. To assess the anti-tumor activity of zanidatamab in the HER2-amplified BTC population, the study’s primary end point is confirmed objective response rate (ORR) by independent central review (ICR).1,2

The secondary study end points include duration of response, the proportion of patients with a DOR at ≥ 16 weeks, disease control rate, progression-free survival, overall survival, and safety. The study will also explore the maximum serum concentration, through concentration of zanidatamab, and the incidence of anti-drug antibodies.

Eligible patients are those aged 18 years of age or older with histologically or cytologically-confirmed BTC that is locally advanced or metastatic and ineligible for curative resection, transplantation, or ablative therapies. Patients are also required to have received at least 1 prior gemcitabine-containing systemic chemotherapy regimen, be positive for HER amplification, have an ECOG performance status of 1 or lowers, adequate organ function, and adequate cardiac function.2

The study excludes patients who have received systemic anti-cancer therapy within 3 weeks of the first dose of zanidatamab in the study and those who have had prior treatment with HER2-targeted therapies. In terms of disease characteristics, patients cannot enroll in the study if they have untreated central nervous system metastases, known leptomeningeal disease, concurrent uncontrolled or active hepatobiliary disorders, or prior or concurrent malignancy, active hepatitis. Other conditions warranting exclusion from the study include infection with human immunodeficiency virus, history of myocardial infarction or unstable angina within 6 months of enrollment in the study, acute or chronic uncontrolled pancreatitis or Child-Pugh class C liver disease, or QTc Fridericia (QTcF) > 470 ms.

Now that HERIZON-BTC-01 has met its target enrollment, 68 locations across the United States, Canada, Chile, China, France, Italy, Spain, and the United Kingdom will soon commence dosing of zanidatamab in patients with HER2-expressing BTC.

“Completing enrollment in our first pivotal trial is a tremendous accomplishment for Zymeworks. I’m extremely proud of our team and our collaborators at BeiGene for their hard work in reaching this milestone ahead of expectations,” said Neil Josephson, MD, chief medical officer. “Currently there are limited options for patients with advanced HER2-amplified biliary tract cancer who experience disease progression after front-line therapy. Zanidatamab has the potential to meet the urgent global clinical need for a safe and effective therapy for patients with this difficult to treat cancer.”


1. Zymeworks reports last patient enrolled in pivotal study of zanidatamab in treatment Of HER2-expressing late-line biliary tract cancer. News release. Zymeworks, Inc. April 28, 2022. Accessed April 29, 2022.

2. A study of ZW25 (Zanidatamab) in subjects with advanced or metastatic her2-amplified biliary tract cancers (HERIZON-BTC-01). Clinicaltrials.gov. Updated April 21, 2022. Accessed April 29, 2022.

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