FDA Grants Priority Review to Zanidatamab for HER2+ Metastatic Biliary Tract Cancer


Zanidatamab has received priority review from the FDA for the treatment of patients with HER2-positive metastatic biliary tract cancer.

Rob Iannone, MD, MSCE

Rob Iannone, MD, MSCE

The FDA has granted priority review to a biologics license application (BLA) seeking the approval of the HER2-targeted bispecific antibody zanidatamab (ZW25) for the treatment of patients with previously treated, unresectable, HER2-positive, locally advanced or metastatic biliary tract cancer.1

The FDA’s target action date under the Prescription Drug User Fee Act is November 29, 2024.

Zanidatamab engages in biparatopic binding with 2 nonoverlapping epitopes of the HER2 receptor, resulting in mechanisms of action including removal of the HER2 protein from the cell surface, HER2 signal blockade, and immune-mediated cytotoxicity.

“The priority review designation for zanidatamab underscores the critical need for new treatment options for patients with locally advanced or metastatic HER2-positive biliary tract cancer, a devastating disease with a poor prognosis,” Rob Iannone, MD, MSCE, executive vice president and global head of research and development at Jazz Pharmaceuticals, said in a news release. “Upon approval, zanidatamab [would] be the first HER2-targeted treatment specifically indicated for these patients, and we look forward to the opportunity to deliver this new treatment option to the biliary tract cancer community.”

The BLA submission was based on findings from cohort 1 of the phase 2b HERIZON-BTC-01 trial (NCT04466891), which evaluated zanidatamab in patients with previously treated, unresectable, locally advanced or metastatic, HER2-positive biliary tract cancer, defined by a positive in situ hybridization result and an immunohistochemistry score of 2+ or 3+. Data presented at the 2023 ASCO Annual Meeting and published in Lancet Oncology demonstrated that HERIZON-BTC-01 met its primary end point with a confirmed overall response rate by blinded independent central review of 41.3% (95% CI, 30.4%-52.8%), and the respective complete response, partial response, stable disease, and progressive disease rates were 1.3%, 40%, 27.5%, and 30%. The disease control rate was 68.8% (95% CI, 57.4%-78.7%).2

At a median follow-up of 12.4 months (range, 7-24), the Kaplan Meier estimated duration of response (DOR) was 12.9 months (range, 1.5 to 16.9+). Additionally, the median progression-free survival was 5.5 months (95% CI, 3.7-7.2; range, 0.3-18.5). Among the 33 patients with confirmed responses at a data cutoff of October 10, 2022, 49% had ongoing responses, and 81.8% had a DOR of at least 16 weeks. Furthermore, the median time to first confirmed response was 1.8 months (range, 1.6-5.5).

Regarding safety, zanidatamab was associated with a tolerable and manageable safety profile. The most common adverse effects (AEs) included diarrhea and infusion-related reactions, which were mostly low grade, reversible, and manageable through supportive care measures. A total of 2.3% of patients had AEs leading to treatment discontinuation. No grade 4 AEs or deaths were determined to be treatment related.

Long-term findings from the trial, including overall survival and updated DOR, will be presented at the 2024 ASCO Annual Meeting.1

The confirmatory phase 3 HERIZON-BTC-302 trial (NCT06282575) is now open for enrollment. This randomized, open-label, global trial will investigate the efficacy and safety of zanidatamab plus standard-of-care (SOC) therapy consisting of cisplatin and gemcitabine with or without the addition of physician’s choice of PD-1/PD-L1 inhibition with durvalumab (Imfinzi) or pembrolizumab (Keytruda) vs SOC chemotherapy with or without a PD-1/PD-L1 inhibitor in the frontline setting in patients with advanced or metastatic HER2-positive biliary tract cancer.1,3

Previously, in 2020, the FDA granted breakthrough therapy designation to zanidatamab for the treatment of patients with previously treated, HER2 gene–amplified biliary tract cancers.4 Zanidatamab monotherapy also previously received FDA fast track designation for patients with refractory biliary tract cancer.1


  1. Zanidatamab granted priority review for HER2-positive metastatic biliary tract cancer. News release. Jazz Pharmaceuticals. May 29, 2024. Accessed May 29, 2024.
  2. Jazz Pharmaceuticals and Zymeworks present positive pivotal phase 2b trial data at ASCO 2023 evaluating zanidatamab in HER2-amplified biliary tract cancers. News release. Jazz Pharmaceuticals. June 2, 2023. Accessed May 29, 2024.
  3. Efficacy and safety of zanidatamab with standard-of-care therapy against standard-of-care therapy for advanced HER2-positive biliary tract cancer. Updated April 8, 2024. Accessed May 29, 2024.
  4. Zymeworks receives FDA breakthrough therapy designation for HER2-targeted bispecific antibody zanidatamab in patients with biliary tract cancer. News release. Zymeworks. November 20, 2020. Accessed May 29, 2024.
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