FDA Grants Breakthrough Designation to Zanidatamab for HER2-Amplified Biliary Tract Cancer


The FDA granted a Breakthrough Therapy designation to zanidatamab as treatment of patients with previously treated HER2-amplified biliary tract cancer.

The FDA has granted a Breakthrough Therapy designation to zanidatamab (formerly ZW25) as treatment of patients with previously treated HER2-amplified biliary tract cancer, announced Zymeworks Inc. in a press release.

This designation is supported by an ongoing phase 2b clinical trial (NCT04466891) of this agent as treatment of patients with locally advanced and/or metastatic HER2-expressing tumors, which include biliary tract cancer, as well as data from a prior study.

“This Breakthrough Therapy designation from the FDA, based on data generated in [patients with] biliary tract cancer 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, in a statement. “This milestone supports our strategy for accelerated approval and will help make zanidatamab available for patients as quickly as possible.”

The company initiated the global registration-enabling study of zanidatamab monotherapy earlier this year for the treatment of patients with HER2-amplified biliary tract cancer. The trial is currently enrolling patients and is designed to support accelerated approval based on the primary end point of overall response rate (ORR). Secondary end points include duration of response, disease control rate, progression-free survival, overall survival, and safety.

The study may also enable submission of a Biologics License Application for zanidatamab as early as 2022. Updated clinical data on single-agent zanidatamab as treatment of patients with biliary tract cancer has been accepted for presentation at the upcoming American Society of Clinical Oncology (ASCO) Virtual Gastrointestinal Cancers Symposium in January 2021.

Patients with a confirmed diagnosis of biliary tract cancer who have locally advanced or metastatic disease, at least 1 prior line of systemic therapy for advanced disease, and who have experienced progression or intolerance after their most recent therapy are eligible to enroll to this open-label, single-arm phase 2b study. To enroll, patients must test positive for HER2 amplification on an in situ hybridization assay, have an ECOG performance status of ≤1, adequate organ function, and adequate cardiac function.

Patients are ineligible to enroll to the clinical trial if they had prior systemic anti-cancer therapy within 3 weeks of the first dose on study or radiotherapy within 2 weeks. They also are ineligible if they have received prior treatment with HER2-targeted therapies, have untreated central nervous system metastases, known leptomeningeal disease, or concurrent uncontrolled or active hepatobiliary disorders.

Zanidatamab is a bispecific antibody that simultaneously binds 2 non-overlapping HER2 epitopes , which is known as biparatopic binding. The agent is under evaluation in multiple phase 1, 2, and registration-enabling trials globally as treatment of patients with solid tumors expressing HER2.

The FDA has previously granted 2 Fast Track designations to the agent, including 1 for refractory biliary tract cancer and 1 in combination with standard chemotherapy for the frontline treatment of gastroesophageal adenocarcinoma. The agent also received Orphan Drug designations for the treatment of biliary tract cancer, gastric cancer, and ovarian cancer from the FDA, as well as from the European Medicines Agency for gastric cancer.

“Biliary tract cancer is a rare and aggressive cancer,” stated 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 biliary tract cancer patients.”

Tumors that overexpress HER2 tend to grow more quickly, as well as spread to other parts of the body. Around 5% to 19% of patients with biliary tract cancer express HER2, which suggests these patients may potentially benefit from a HER2-targeted therapy. At this time, no HER2-targeted therapies are approved for the treatment of biliary tract cancer.


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://bwnews.pr/2Jur8HK

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