HER2-Targeted Therapy Shows Promising Results in Rare Bile Duct Cancers

• HER2-positive metastatic biliary tract cancer (BTC) is a rare and aggressive cancer with limited treatment options
• Final results from the HERIZON-BTC-01 clinical trial, the largest study of a HER2-targeted drug in BTC, show zanidatamab has clinically meaningful responses
• The targeted therapy demonstrated durable responses, longer survival and tumor shrinkage in some BTC patients
• Zanidatamab was granted accelerated FDA approval for treating HER2-positive BTC in Nov. 2024, based on these trial results

Newswise — Zanidatamab, a bispecific HER2-targeted antibody, delivered clinically meaningful and durable responses for patients with HER2-positive biliary tract cancer (BTC), according to final results from the HERIZON-BTC-01 clinical trial led by researchers at The University of Texas MD Anderson Cancer Center.

In this clinical trial, zanidatamab demonstrated an objective response rate of 41.3% and a median duration of response of 15.5 months, while patients whose tumors showed strongest levels of HER2 overexpression experienced even greater benefit – a 51.6% response rate and a median duration of response of 18.1 months.

Results from this trial, led by Shubham Pant, M.D., professor of Gastrointestinal Medical Oncology and Investigational Cancer Therapeutics, were published in JAMA Oncology. Initial trial results were first reported in The Lancet Oncology in June 2023. 

“The observed objective response rate, prolonged duration of response, and consistent activity in IHC3+ tumors underscores HER2 as a valid therapeutic target in biliary tract cancer and support the emerging role of zanidatamab in the treatment paradigm,” Pant said.

What is the significance of the HERIZON-BTC-01 trial results?

Unresectable or metastatic biliary tract cancer (BTC) is a rare, aggressive cancer and has very limited treatment options once standard therapies stop working. These findings represent the largest HER2-targeted clinical database in BTC and provide the longest follow-up reported to date.

In a cohort of 80 patients, those who responded to zanidatamab reported meaningful improvements in their symptoms, particularly in pain levels. Many experienced either reductions or stabilization of pain compared with their baseline, indicating the treatment not only controlled tumor growth but also helped alleviate disease-related discomfort. In addition, patients who remained on the study long enough to complete follow-up assessments showed higher rates of overall symptom control.

What are the implications of this trial for patients with biliary tract cancers?

Zanidatamab is a bispecific antibody that binds to two distinct sites on the HER2 receptor, enabling it to more effectively inhibit cancer cell growth and promote immune-mediated elimination of tumor cells compared with traditional HER2-targeted therapies.

These trial results directly supported the Food and Drug Administration (FDA) accelerated approval of zanidatamab for adults with previously treated, unresectable or metastatic IHC3+ biliary tract cancer. The durability and safety profile suggest zanidatamab has strong therapeutic potential for this difficult-to-treat cancer.

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This trial was supported by was supported by BeOne Medicines, Jazz Pharmaceuticals, and Zymeworks. A full list of collaborating authors and their disclosures can be found with the paper in JAMA Oncology.