Dr Harding on the FDA Approval of Zanidatamab for HER2+ Biliary Tract Cancer

“[This approval] offers a new treatment option for patients with [a] very difficult disease that has notable antitumor activity and…associated safety and tolerability.”

James J. Harding, MD, associate attending physician, Memorial Sloan Kettering Cancer Center, discusses the significance of the FDA approval of zanidatamab-hrii (Ziihera) for patients with pretreated, unresectable or metastatic HER2-positive biliary tract cancer.

On November 20, 2024, the FDA granted accelerated approval to zanidatamab for the treatment of adult patients with previously treated, unresectable or metastatic HER2-positive (immunohistochemistry 3+ by central assessment) biliary tract cancer. This regulatory decision was based on findings from the phase 2b HERIZON-BTC-01 trial (NCT04466891). In the trial, patients with HER2-amplified, locally advanced unresectable or metastatic biliary tract cancer (including gallbladder cancer or intra-/extra-hepatic cholangiocarcinoma) who had received prior gemcitabine-containing therapy were treated with intravenous zanidatamab at a dose of 20 mg/kg every 2 weeks (n = 62). These patients achieved an overall response rate of 52% (95% CI, 39%-65%). The estimated median duration of response in this population was 14.9 months (95% CI, 7.4-not estimable).

Among the 80 patients in the safety-evaluable population, the most common adverse effects (AEs) included diarrhea, infusion-related reaction, abdominal pain, and fatigue. Serious AEs occurred in 53% of the 80 safety-evaluable patients. The most common serious AEs included biliary obstruction (15%), sepsis (8%), biliary tract infection (8%), pneumonia (5%), gastric obstruction (3.8%), diarrhea (3.8%), and fatigue (2.5%).

The ongoing, confirmatory phase 3 HERIZON-BTC-302 trial (NCT06282575) is investigating zanidatamab plus standard-of-care (SOC) therapy compared with SOC therapy alone in the frontline setting in patients with HER2-positive biliary tract cancer.

This approval ushers in an era of advancement for the treatment of patients with HER2-positive biliary tract cancer and is the first accelerated approval of a HER2-targeted agent in this disease, Harding begins. Zanidatamab is a HER2-directed bispecific antibody that has demonstrated antitumor activity and a tolerable safety profile in patients with HER2-positive disease, which has historically been difficult to manage, he concludes.