FDA Grants Zanidatamab Breakthrough Status in HER2+ Biliary Tract Cancer


November 30, 2020 - The FDA has granted a breakthrough therapy designation to zanidatamab for the treatment of patients with HER2 gene–amplified biliary tract cancer who have received prior therapy.

The FDA has granted a breakthrough therapy designation to zanidatamab for the treatment of patients with HER2 gene–amplified biliary tract cancer (BTC) who have received prior therapy.

The designation is based on an ongoing phase 1 study (NCT02892123) of zanidatamab in patients with locally advanced, unresectable and/or metastatic HER2-expressing cancers, including BTC. Findings from the trial will be presented at the 2021 Gastrointestinal Cancers Symposium in January.

"This breakthrough therapy designation from the FDA, based on data generated in BTC patients treated in the initial phase 1 trial, is recognition of the potential of zanidatamab to provide a new approach to cancer treatment," said Diana Hausman, MD, chief medical officer at Zymeworks, the developer of zanidatamab. "This milestone supports our strategy for accelerated approval and will help make zanidatamab available for patients as quickly as possible."

BTC comprises approximately 3% of all adult cancers and are linked with a poor prognosis. On an international scale, 210,000 people are diagnosed with BTC annually. Additionally, at least 65% of BTCs, when diagnosed, cannot be surgically resected and those that are typically have a high recurrence rate. Current systemic options are limited for those who progress on first-line chemotherapy. 

Zanidatamab is a bispecific antibody designed with biparatopic binding, which results in dual HER2 signal blockade, increased binding, removal of HER2 protein from the cell surface, and potent effector function, which can lead to encouraging activity in patients.

The FDA has previously granted 2 fast track designations to zanidatamab; one designation is for use as a single agent in patients with refractory BTC, while the second is for frontline use in combination with standard chemotherapy in patients with gastroesophageal adenocarcinoma.

In the 3-part, phase 1 study, investigators are evaluating the maximum-tolerated dose of zanidatamab, as well as the safety, tolerability, and efficacy of the agent alone and in combination with select chemotherapy options, such as paclitaxel, capecitabine (Xeloda), or vinorelbine. Zanidatamab is either administered intravenously once weekly, once every 2 weeks, or once every 3 weeks.

Earlier in 2020, the company previously initiated an international phase 2b registration-enabling study (NCT04466891) of single-agent zanidatamab in approximately 100 patients with previously treated HER2gene-amplified BTC, including intrahepatic cholangiocarcinoma, extrahepatic cholangiocarcinoma, and gallbladder cancer. The primary end point of the trial is objective response rate, while secondary end points include duration of response and safety.

To be eligible for enrollment, patients must have received at least 1 prior regimen of systemic therapy for advanced disease, have HER2-amplified disease, be at least 18 years old, have an ECOG performance status of 0 or 1, and adequate organ and cardiac function.

Those who previously received anticancer therapy within 3 weeks of their first zanidatamab dose, had prior treatment with HER2-targeted agents, have untreated and/or symptomatic central nervous system metastases, known leptomeningeal disease, concurrent uncontrolled or active hepatobiliary disorders, have a prior or concurrent invasive malignancy, active hepatitis, HIV-1 or HIV-2 infection, and acute or chronic uncontrolled pancreatitis or Child-Pugh Class C liver disease cannot be enrolled on the study.

The study, which is currently accruing patients, is designed to serve as the basis for an accelerated approval of zanidatamab in this setting. The submission of a biologics license application could occur as early as 2022, Zymeworks added.

"BTC is a rare and aggressive cancer," said James Priour, senior vice president, commercial, at Zymeworks. "Receiving this designation from the FDA is testament to the potential of zanidatamab to be the first HER2-targeting therapy approved for metastatic BTC patients."

Zymeworks is developing zanidatamab in multiple international studies as a targeted therapeutic for patients with solid tumors that express HER2, including but not limited to cancers of the breast, lung, ovaries, and colon.


Zymeworks Receives FDA Breakthrough Therapy Designation for HER2-Targeted Bispecific Antibody Zanidatamab in Patients with Biliary Tract Cancer. News release. Zymeworks Inc. November 30, 2020. Accessed November 30, 2020. https://yhoo.it/2Vizh51

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