FDA Approves Zanidatamab-hrii for HER2+ Biliary Tract Cancer

Currently, chemotherapy remains a common treatment for biliary tract cancers, which have a limited survival rate. | Image Credit: syahrir - stock.adobe.com

The FDA granted accelerated approval to zanidatamab-hrii (Ziihera) for the treatment of adults with previously treated, unresectable or metastatic HER2-positive biliary tract cancer.¹

Zanidatamab will be manufactured by Zymeworks Inc., a clinical-stage biotechnology company, along with Jazz Pharmaceuticals.² The approval was based on the results from the HERIZON-BTC-01 trial, which analyzed zanidatamab as a single agent in patients with previously treated HER2-positive biliary tract cancer.

Biliary tract cancers encompass an estimated 3% of all gastrointestinal cancers and have a limited survival rate.³ These types of cancers include intrahepatic cholangiocarcinoma, extrahepatic cholangiocarcinoma, gallbladder cancer, and ampullary carcinoma. While targeted therapies exist for biliary tract cancers, chemotherapy remains a highly common treatment for patients.

"Metastatic biliary tract cancer, BTC [biliary tract cancer], places a significant burden on patients, affecting their quality of life and their emotional and mental well-being, as well as that of their families," Stacie Lindsey, chief executive officer and founder of the Cholangiocarcinoma Foundation, said in a press release.¹

The study enrolled 87 patients with HER2-amplified, locally advanced unresectable or metastatic biliary tract cancer in 2 cohorts. Patients received 20 mg/kg zanidatamab intravenously every 2 weeks until disease progression or unacceptable toxicity, for an average of 5.6 months.

The first cohort included patients who were immunohistochemistry (IHC) 2+/3+ (n = 80) while the second cohort included patients who were IHC 0/1+ (n = 7). Tumors were reassessed every 8 weeks. Primary end points included the objective response rate by independent central review in cohort 1 while efficacy and safety outcomes were the secondary end points.

“Zanidatamab has demonstrated antitumor activity and is now a new option for patients with HER2-positive biliary tract cancer,” commented James Harding, MD, gastrointestinal oncologist and early drug development specialist at Memorial Sloan Kettering Cancer Center.¹

The accelerated approval of zanidatamab was granted based on the 52% objective response rate among patients, as well as the 14.9 months average duration of treatment. The phase 3 HERIZON-BTC-302 trial is ongoing and is looking to evaluate zanidatamab combined with standard-of-care therapy vs standard-of-care therapy alone in the first-line treatment setting.

Common adverse reactions among patients who received zanidatamab included diarrhea, infusion-related reaction, abdominal pain, and fatigue. Serious adverse reactions included biliary obstruction, biliary tract infection, sepsis, pneumonia, diarrhea, gastric obstruction, and fatigue. Only 1 patient had a fatal adverse reaction of hepatic failure and 2.5% of patients permanently discontinued due to adverse reactions.

Zanidatamab is currently being investigated for its potential in treating additional tumor types. Phase 3 trials are underway to explore its efficacy in gastroesophageal adenocarcinomas (GEAs) and metastatic breast cancer. The HERIZON-GEA-01 trial is evaluating zanidatamab combined with chemotherapy, with or without tislelizumab, as a first-line treatment for advanced/metastatic HER2-positive GEAs.

Additionally, the EmpowHER-303 trial is assessing the combination of zanidatamab and physician's choice of chemotherapy for patients with HER2-positive metastatic breast cancer who have progressed on or are intolerant to prior trastuzumab deruxtecan therapy.

References

1. Jazz Pharmaceuticals announces US FDA approval of Ziihera (zanidatamab-hrii) for the treatment of adults with previously treated, unresectable or metastatic HER2-positive (IHC 3+), biliary tract cancer (BTC). News release. PR Newswire; November 20, 2024. Accessed November 21, 2024. https://www.prnewswire.com/news-releases/jazz-pharmaceuticals-announces-us-fda-approval-of-ziihera-zanidatamab-hrii-for-the-treatment-of-adults-with-previously-treated-unresectable-or-metastatic-her2-positive-ihc-3-biliary-tract-cancer-btc-302312216.html

2. FDA grants US approval of Ziihera (zanidatamab-hrii) for the treatment of adults with previously treated, unresectable or metastatic HER2-positive (IHC 3+) biliary tract cancer (BTC). News release. Zymeworks; November 21, 2024, Accessed November 21, 2024. https://ir.zymeworks.com/news-releases/news-release-details/fda-grants-us-approval-ziiherar-zanidatamab-hrii-treatment

3. Ayasun R, Ozer M, Sahin I. The role of HER2 status in the biliary tract cancers. Cancers (Basel). 2023;15(9):2628. doi:10.3390/cancers15092628