The FDA has granted accelerated approval to zanidatamab-hrii (Ziihera, Jazz Pharmaceuticals) for the treatment of adult patients with previously treated, unresectable, or metastatic HER2-positive biliary tract cancer. This approval marks a significant advancement for patients with this aggressive cancer who have limited treatment options after first-line therapy.
The approval was based on the results of the phase 2B HERIZON-BCT-01 trial, which evaluated zanidatamab monotherapy in patients with HER2-amplified, locally advanced unresectable or metastatic biliary tract cancer. The study included 87 participants, with a median age of 64 years, and showed promising efficacy in a heavily pre-treated population.
Efficacy and Safety Data
The HERIZON-BCT-01 trial demonstrated an objective response rate (ORR) of 52% (95% CI, 39-65) among 62 patients with IHC3+ HER2 status, as assessed by independent central review. The estimated median duration of response was 14.9 months (95% CI, 7.4 to not estimable). All patients had received gemcitabine-containing therapy, and the median number of prior lines of therapy was one (interquartile range, 1-2).
According to James J. Harding, MD, associate attending physician at Memorial Sloan Kettering Cancer Center, "Zanidatamab has demonstrated antitumor activity and is now a new option for patients with HER2-positive biliary tract cancer. I look forward to continued and successful drug development for patients with biliary tract cancer."
Safety analyses showed that 96.6% of patients experienced any treatment-emergent adverse event, and 72.4% experienced treatment-related adverse events. The most common adverse events were diarrhea (36.8%), infusion-related reaction (33.3%), ejection fraction decrease (10.3%), and nausea (9.2%). Grade 3/grade 4 treatment-related adverse events occurred in 20.7% of patients, with diarrhea (4.6%) and ejection fraction decrease (3.4%) being the most frequent.
Biliary Tract Cancer and HER2 Overexpression
Biliary tract cancer is a heterogeneous group of malignancies, including gallbladder cancer, extrahepatic cholangiocarcinoma, and intrahepatic cholangiocarcinoma. The prognosis for patients with advanced disease is poor, with a five-year survival rate of less than 5% for those with metastatic disease.
HER2 overexpression or gene amplification rates vary among the different types of biliary tract cancer: 4% to 5% for intrahepatic cholangiocarcinoma, 17% to 19% for extrahepatic cholangiocarcinoma, and 19% to 31% for gallbladder cancer.
Ongoing Research
Continued approval of zanidatamab may be contingent on verification of the therapy's benefit in a confirmatory trial. A randomized phase 3 trial (HERIZON-BTC-302) is currently underway to evaluate zanidatamab in combination with standard therapy as a first-line treatment for HER2-positive biliary tract cancer. This trial aims to further establish the role of zanidatamab in improving outcomes for patients with this challenging disease.
