Zanidatamab Shows Promise in HER2-Expressing Biliary Tract Cancers


Positive topline data from the phase 2b HERIZON-BTC-01 trial indicate zanidatamab may improve outcomes for patients with HER2-amplified and expressing biliary tract cancers.

The bispecific antibody zanidatamab demonstrated promising responses in patients with previously treated HER2-amplified and expressing biliary tract cancers, according to topline data from the phase 2b HERIZON-BTC-01 trial (NCT04466891) recently published by Zymeworks.

These early data include a confirmed objective response rate (ORR) of 41.3% (95% CI, 30.4-52.8) as assessed by independent central review in patients who received the agent, as well as a median duration of response of 12.9 months (95% CI, 5.95-not reached [NR]).

Additionally, the observed safety profile aligned with findings from previous single-agent studies and no new safety signals were reported.

The study’s full results will be presented at an upcoming medical meeting in 2023.

“Through our work with the community [of patients with biliary tract cancers], we see first-hand the challenge these patients face in not only getting a diagnosis, but in the limited treatment options available,” Stacie Lindsey, founder and CEO of the Cholangiocarcinoma Foundation, said in the press release.. “Each investigative trial begins to close the gap on this high unmet medical need by helping to bring more treatment options to patients [with biliary tract cancers] and we’re looking forward to watching zanidatamab’s progression through the global regulatory review process.”

Zanidatamab simultaneously binds 2 non-overlapping epitopes of HER2 in a process known as biparatopic binding. As such, the agent has multiple mechanisms of action, including dual HER2 signal blockade, increased removal of HER2 protein from the cell surface, and potent effector function. The antibody has thereby shown encouraging antitumor activity.

The phase 2 HERIZON-BTC-01 trial is an open-label, multicenter, single-arm study assessing zanidatamab in patients with inoperable and advanced or metastatic biliary tract cancers, including intra- and extra-hepatic cholangiocarcinoma as well as gallbladder cancer. HER2 amplification, as determined by in situ hybridization in tumor tissue, was an inclusion criterion for all enrolled subjects, who were assigned to either cohort 1— tumor tissue showing HER2 immunohistochemistry (IHC) 2+ or 3+ staining—or cohort 2—tumor tissue showing HER2 IHC 0 or 1+ staining. The former was the primary efficacy cohort.

Patients must have received at least 1 prior systemic chemotherapy regimen containing gemcitabine to enroll on HERIZON-BTC-01; they also must have experienced disease progression following treatment or developed intolerance to their most recent prior therapy. They must also have an ECOG performance status of 0 or 1.

Exclusion criteria included treatment with any systemic anticancer therapy in the 3 weeks prior to the first dose of zanidatamab or treatment with radiotherapeutic in the 2 weeks prior. Patients also were not permitted to have any history of treatment with HER2-targeted agents, nor any untreated or symptomatic central nervous system (CNS) metastases. Radiation treatment for CNS metastases in the 4 weeks prior to the first was is also grounds for exclusion.

The ongoing phase 3 HERIZON-GEA-01 trial (NCT05152147) is also assessing zanidatamab with or without tislelizumab in patients with HER2-positive advanced or metastatic gastric and esophageal cancers.


Zymeworks announces positive topline data in the pivotal HERIZON-BTC-01 trial of zanidatamab. News Release. Zymeworks. December 19, 2022. Accessed December 19, 2022.

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