FDA Approves Zanidatamab (Ziihera) for HER2-Positive Biliary Tract Cancer
核心洞察
The FDA has granted accelerated approval to zanidatamab-hrii (Ziihera) for adults with previously treated, unresectable or metastatic HER2 (搜索)-positive biliary tract cancer (搜索).
The approval was based on the HERIZON-BTC-01 trial, which demonstrated a 52% objective response rate and a 14.9-month average duration of treatment with zanidatamab.
Zanidatamab, developed by Zymeworks Inc. and Jazz Pharmaceuticals, offers a new targeted therapy option for biliary tract cancers, where chemotherapy is currently a common treatment.
The FDA has granted accelerated approval to zanidatamab-hrii (Ziihera) for the treatment of adult patients with previously treated, unresectable or metastatic HER2 (搜索)-positive biliary tract cancer (搜索) (BTC). This approval marks a significant advancement in the treatment landscape for these aggressive cancers, which often have limited survival rates and rely heavily on chemotherapy. The decision was based on data from the HERIZON-BTC-01 trial, highlighting the drug's potential to address a critical unmet need.
HERIZON-BTC-01 Trial Results
The HERIZON-BTC-01 trial evaluated zanidatamab as a single agent in patients with HER2 (搜索)-positive BTC who had previously undergone treatment. The study enrolled 87 patients with HER2-amplified, locally advanced unresectable or metastatic BTC. Patients received 20 mg/kg of zanidatamab intravenously every two weeks until disease progression or unacceptable toxicity, with an average treatment duration of 5.6 months.
The primary endpoint was the objective response rate (ORR) as assessed by independent central review in the cohort of patients with immunohistochemistry (IHC) 2+/3+ HER2 (搜索) expression (n = 80). Results showed a 52% ORR, with an average duration of treatment of 14.9 months. These findings underscore the clinical benefit of zanidatamab in this patient population, as stated by James Harding, MD, a gastrointestinal oncologist at Memorial Sloan Kettering Cancer Center.
Safety and Tolerability
Common adverse reactions observed in patients treated with zanidatamab included diarrhea, infusion-related reactions, abdominal pain, and fatigue. Serious adverse reactions included biliary obstruction, biliary tract infection, sepsis, pneumonia, diarrhea, gastric obstruction, and fatigue. One patient experienced a fatal adverse reaction of hepatic failure, and 2.5% of patients discontinued treatment due to adverse reactions.
Biliary Tract Cancer Context
Biliary tract cancers, encompassing intrahepatic cholangiocarcinoma, extrahepatic cholangiocarcinoma, gallbladder cancer, and ampullary carcinoma, account for approximately 3% of all gastrointestinal cancers. These cancers pose a significant burden on patients, affecting their quality of life and overall well-being. Stacie Lindsey, CEO of the Cholangiocarcinoma Foundation, emphasized the importance of new treatment options to address these challenges.
Ongoing and Future Research
Zanidatamab is currently under investigation for other tumor types beyond biliary tract cancer (搜索). The phase 3 HERIZON-BTC-302 trial (NCT06282575) is underway to evaluate zanidatamab combined with standard-of-care therapy versus standard-of-care therapy alone in the first-line treatment setting. Additionally, trials such as HERIZON-GEA-01 are exploring zanidatamab in gastroesophageal adenocarcinomas (搜索), and EmpowHER-303 is assessing its efficacy in HER2 (搜索)-positive metastatic breast cancer (搜索).
Development and Manufacturing
Zanidatamab is being developed and manufactured by Zymeworks Inc. in collaboration with Jazz Pharmaceuticals. This partnership aims to expand the availability of this targeted therapy to patients in need.