Zanidatamab BLA Receives FDA Priority Review for HER2+ Biliary Tract Cancer

• Zanidatamab (ZW25) is being considered for FDA approval as a treatment for HER2-positive biliary tract cancer (BTC).
• Data from a clinical trial (HERIZON-BTC-01; NCT04466891) showed promising results for zanidatamab.
• Zanidatamab could be the first HER2-targeted treatment specifically approved for this cancer in the US.

The FDA has accepted and granted priority review of the biologics license application for zanidatamab for the treatment of patients with previously treated, HER2-positive, unresectable, locally advanced or metastatic BTC.¹

Data from the phase 2b HERIZON-BTC-01 trial support this regulatory decision as cohort 1 of the study, which consisted of patients with HER2-positive BTC (n = 80), showed a confirmed objective response rate (ORR) of 41.3% (95% CI, 30.4%-52.8%) by independent review committee (IRC) assessment. This included a complete response (CR) rate of 1.3% and a partial response (PR) rate of 40%. Further, 27.5% of patients had stable disease (SD), 30% achieved progressive disease (PD), and 1.3% were not evaluable for response.²

A Prescription Drug User Fee Act (PDUFA) target action date of November 29, 2024, has been set.¹

"The priority review designation for zanidatamab underscores the critical need for new treatment options for patients with locally advanced or metastatic HER2-positive BTC, a devastating disease with a poor prognosis,” said Rob Iannone, MD, MSCE, executive vice president, global head of research and development of Jazz Pharmaceuticals, in a press release. "Upon approval, zanidatamab will 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 BTC community."

Long-term follow-up data from the phase 2b HERIZON-BTC-01 trial are expected to be presented at the upcoming American Society of Clinical Oncology Annual Meeting 2024.

Zanidatamab is an investigational HER2-targeted bispecific antibody. The agent works to simultaneously bind 2 nonoverlapping epitopes of the HER2 receptor, which results in multiple mechanisms of action, including dual HER2 signal blockade, removal of HER2 protein from the cell surface, and immune-mediated cytotoxicity leading to encouraging antitumor activity in patients.

Previously, the FDA granted a breakthrough therapy designation for zanidatamab in those with previously treated HER2 gene-amplified BTC, and 2 fast track designations were also given to zanidatamab, including as a single agent for refractory BTC and in combination with standard-of-care (SOC) chemotherapy for the first-line treatment of patients with gastroesophageal adenocarcinoma. Zanidatamab was also granted an orphan drug designation from FDA for the treatment of BTC and gastroesophageal adenocarcinoma. An orphan drug designation was granted to the agent from the European Medicines Agency for the patients of BTC and gastric cancer, and the Center for Drug Evaluation in China also granted zanidatamab a breakthrough therapy designation.

Zanidatamab is being evaluated in multiple trials for the treatment of a variety of solid tumors that express HER2. Another study, the HERIZON-BTC-302, global, open-label, randomized, phase 3 trial (NCT06282575), is also assessing the safety and efficacy of zanidatamab given with SOC therapy vs SOC therapy alone for the treatment of first-line advanced or metastatic HER2-positive BTC. The trial is ongoing, enrolling patients, and anticipated to serve as the confirmatory trial for zanidatamab in BTC.

REFERENCES:

1. Zanidatamab granted priority review for HER2-positive metastatic biliary tract cancer. News release. Jazz Pharmaceuticals plc. May 29, 2024. Accessed May 29, 2024. https://tinyurl.com/mr4c2d6n

2. Harding JJ, Fan J, Oh D, et al. Zanidatamab for HER2-amplified, unresectable, locally advanced or metastatic biliary tract cancer (HERIZON-BTC-01): a multicentre, single-arm, phase 2b study. Lancet Oncol. 2023;24(7):772-782. doi: 10.1016/S1470-2045(23)00242-5