Zanidatamab Gains Accelerated Approval by FDA for Metastatic HER2+ BTC

Ziihera (zanidatamab), an intravenous injection for patients with previously treated, unresectable, or metastatic HER2-positive biliary tract cancer (BTC), has received accelerated approval by the U.S. Food and Drug Administration based on positive results from the HERIZON-BTC-01 trial.

Zanidatamab benefits patients by binding to HER2, resulting in a reduction of the receptor on the tumor cell surface. It induces cell growth in vitro and in vivo, as well as tumor growth inhibition.

The open-label, phase IIb HERIZON-BTC-01 trial evaluated the Jazz Pharmaceuticals therapy in 62 patients with HER2-positive BTC who had received prior gemcitabine-containing therapy. Patients were administered zanidatamab 20mg/kg intravenously every two weeks. The trial demonstrated a 52% objective response rate and a median duration of response of 14.9 months.

The most common adverse reactions (≥ 20% of patients) included diarrhea, infusion-related reaction, abdominal pain, and fatigue. Serious adverse reactions (> 2% of patients) included biliary obstruction (15%), biliary tract infection (8%), sepsis (8%), pneumonia (5%), diarrhea (3.8%), gastric obstruction (3.8%), and fatigue (2.5%). One patient experienced a fatal adverse reaction of hepatic failure, and permanent discontinuation occurred in 2.5% of patients due to an adverse reaction.

HERIZON-BTC-01 marks the largest phase IIb clinical trial to date for patients with previously treated HER2-positive disease. Zanidatamab has also received a Fast Track designation as a single agent for refractory BTC.

The phase III HERIZON-BTC-302 trial is currently ongoing to assess the efficacy of zanidatamab in combination with standard of care against standard of care alone in the first-line setting.