FDA Grants Accelerated Approval to Zanidatamab for HER2-Positive Biliary Tract Cancer
Key Insights
The FDA has granted accelerated approval to Ziihera (zanidatamab-hrii (search)) for adults with previously treated, unresectable or metastatic HER2 (search)-positive biliary tract cancer (search).
Zanidatamab-hrii (search) is the first and only dual HER2 (search)-targeted bispecific antibody treatment approved for this specific indication, addressing a critical unmet need.
The approval was based on the Phase 2b HERIZON-BTC-01 trial, which demonstrated a 52% overall response rate and a median duration of response of 14.9 months.
Jazz Pharmaceuticals' Ziihera (zanidatamab-hrii (search)) has received accelerated approval from the U.S. Food and Drug Administration (FDA) for the treatment of adult patients with previously treated, unresectable, or metastatic HER2 (search)-positive (IHC 3+) biliary tract cancer (search) (BTC). This approval marks zanidatamab-hrii as the first and only dual HER2-targeted bispecific antibody available for this indication.
The approval was primarily based on the results of the Phase 2b HERIZON-BTC-01 trial. This trial demonstrated a 52% overall response rate (ORR) in patients treated with zanidatamab-hrii (search), with a median duration of response (DoR) of 14.9 months as determined by independent central review. These findings highlight the potential of zanidatamab-hrii to provide meaningful clinical benefit in a patient population with limited treatment options.
Clinical Efficacy and Safety
The HERIZON-BTC-01 trial enrolled 87 patients with HER2 (search)-positive BTC. The study's results, published in The Lancet Oncology, showed promising antitumor activity. The safety of zanidatamab-hrii (search) was evaluated across the HERIZON-BTC-01 and ZWI-ZW25-101 trials, which included 109 patients with BTC and 124 patients with other cancers. Common adverse reactions observed in the HERIZON-BTC-01 trial included diarrhea (50%), abdominal pain (29%), and fatigue (24%).
Dosage and Administration
The recommended dosage of zanidatamab-hrii (search) is 20 mg/kg, administered as an intravenous infusion every two weeks. Premedication with acetaminophen, an antihistamine, and a corticosteroid is recommended 30 to 60 minutes before each infusion to reduce the risk of infusion-related reactions. The drug is supplied as a powder that requires reconstitution and dilution with sterile water prior to administration.
Biliary Tract Cancer and HER2 Overexpression
Biliary tract cancer (search) affects the bile ducts within the gallbladder, liver, and small intestine. When the tumor cells overexpress the HER2 (search) protein, the cancer is classified as HER2-positive, leading to rapid tumor growth. The prognosis for metastatic BTC is poor, with a five-year survival rate of less than 5%.
Ongoing Research
A Phase 3 trial, HERIZON-BTC-302, is currently underway to evaluate the effectiveness of zanidatamab-hrii (search) in combination with standard-of-care therapy. Additionally, the efficacy of zanidatamab-hrii is being investigated in metastatic breast cancer (search) and gastroesophageal adenocarcinomas (search).