FDA Approves Zanidatamab (Ziihera®) for HER2-Positive Biliary Tract Cancers
Key Insights
The FDA granted accelerated approval to zanidatamab (Ziihera®) for advanced biliary tract cancers (search) with high HER2 (search) expression that are unresponsive to chemotherapy.
Zanidatamab, a bispecific antibody, uniquely binds to HER2 (search), blocking growth signals, causing protein degradation, and triggering immune cell attacks on cancer cells.
Clinical trial HERIZON-BTC-01 showed a 41.3% objective response rate in patients treated with zanidatamab, with manageable side effects like diarrhea and weakened heart pumping ability.
The U.S. Food and Drug Administration (FDA) has granted accelerated approval to zanidatamab (Ziihera®) for the treatment of advanced or metastatic HER2 (search)-positive biliary tract cancers (search) (BTC) that have progressed following prior chemotherapy. This approval marks a significant advancement for patients with these rare and aggressive tumors affecting the bile ducts and gallbladder.
Mechanism of Action
Zanidatamab is a bispecific antibody that targets the HER2 (search) protein, which is overexpressed in a subset of biliary tract cancers (search), as well as in some breast, lung, and stomach cancers. Unlike other HER2-targeted therapies, zanidatamab binds to HER2 at two distinct sites. This dual binding mechanism not only blocks HER2 signaling, preventing tumor cell growth and survival, but also induces HER2 protein degradation and activates the immune system to attack cancer cells.
Clinical Trial Results
The approval was based on the results of the HERIZON-BTC-01, a global phase 2b clinical trial. The trial enrolled 87 patients with HER2 (search)-amplified BTC from the United States, Europe, and Asia. Key findings from the study, published in The Lancet Oncology, include:
- A confirmed objective response rate (ORR) of 41.3%, indicating that tumors shrank by a measurable amount in a significant proportion of patients.
- Treatment-related adverse events were observed in 18% of participants, including diarrhea and decreased heart function. No severe side effects or treatment-related deaths were reported.
Expert Commentary
"These cancers are rare, making up just 3% of all gastrointestinal cancers," said Dr. James J. Harding, a gastrointestinal medical oncologist and early drug development specialist at Memorial Sloan Kettering Cancer Center (MSK), who co-led the clinical trial. "But MSK is a major center for biliary tract cancer research and treatment. We are evaluating multiple novel treatment approaches, and a key focus of our work is on molecular testing of these tumors and finding ways to target them with precision medicine."
Patient Experience
Rob, a 42-year-old patient with stage 4 gallbladder cancer (search), participated in the clinical trial after his cancer progressed following chemotherapy. Treatment with zanidatamab led to tumor shrinkage, and he experienced fewer side effects compared to chemotherapy. Although his cancer eventually progressed, he was subsequently treated with trastuzumab deruxtecan, another HER2 (search)-targeted therapy, leading to further tumor regression. Rob's experience highlights the potential benefits of targeted therapies in patients with HER2-positive biliary tract cancers (search).
Implications for Treatment
The approval of zanidatamab provides a new treatment option for patients with HER2 (search)-positive biliary tract cancers (search) who have limited alternatives. This approval underscores the importance of HER2 testing in BTC to identify patients who may benefit from this targeted therapy.