Zanidatamab Earns FDA Priority Review in HER2+ Biliary Tract Cancer

Supporting findings for the BLA came from cohort 1 of the phase 2b HERIZON-BTC-01 trial (NCT05152147), in which investigators evaluated zanidatamab for patients who received prior treatment for unresectable, locally advanced, or metastatic HER2-positive BTC.

The FDA has granted priority review to a biologics license application (BLA) for zanidatamab as a treatment for HER2-positive, previously treated, unresectable, locally advanced, or metastatic biliary tract cancer (BTC), according to a press release from the developers, Jazz Pharmaceuticals, Inc.¹

The regulatory agency has set a Prescription Drug User Fee Act date of November 29, 2024, for its decision on approving zanidatamab for this patient population.

The investigational HER2-targeting bispecific antibody zanidatamab is designed to facilitate biparatopic binding in the HER2 receptor, yielding dual HER2 signal blockade, ejection of the HER2 protein from the cell surface, and immune-mediated cytotoxicity that can augment antitumor activity.

Supporting findings for the BLA came from cohort 1 of the phase 2b HERIZON-BTC-01 trial (NCT05152147), in which investigators evaluated zanidatamab for patients who received prior treatment for unresectable, locally advanced, or metastatic HER2-positive BTC. Previous data from cohort 1 of the trial, which included patients who were in situ hybridization positive with immunohistochemistry (IHC) scores of 2+ or 3+, were published in the Lancet Oncology.²

At the time of the analysis, treatment with zanidatamab produced a confirmed objective response rate (ORR) of 41.3% (95% CI, 30.4%-52.8%) per independent central review and investigator assessment. Additionally, the median time to first response was 1.8 months (95% CI, 1.7-2.0) per independent central review and 1.8 months (95% CI, 1.8-2.0) per investigator assessment, and the median duration of response (DOR) was 12.9 months (95% CI, 6.0-not estimable [NE]) and 11.1 months (95% CI, 5.6-14.1), respectively.

The median progression-free survival (PFS) was 5.5 months (95% CI, 3.7-7.2) according to an independent central review and 5.4 months (95% CI, 3.6-7.2) based on investigator assessment. Investigators plan to present additional long-term follow-up results as well as data related to overall survival (OS) at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting.

Data highlighted grade 3 treatment-related adverse effects (TRAEs) in 18% of patients in cohort 1. Specifically, these toxicities included diarrhea (5%), ejection fraction decreases (3%), and anemia (2%).

“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,” Rob Iannone, MD, MSCE, executive vice president and global head of research and development at Jazz Pharmaceuticals, said in the press release.¹ “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.”

In the international, multi-center, single-arm HERIZON-BTC-01 trial, patients were assigned to receive zanidatamab at 20 mg/kg on days 1 and 15 of each 28-day cycle.

The trial’s primary end point was confirmed ORR per independent central review in cohort 1. Secondary end points included DOR, disease control rate, and OS.

Patients 18 years and older with pathologically confirmed, previously treated, unresectable, locally advanced or metastatic, HER2-amplified gallbladder cancer, intrahepatic cholangiocarcinoma, or extrahepatic cholangiocarcinomawere able to enroll on the trial. Additional eligibility criteria included having 1 or more measurable lesions per RECIST v1.1 guidelines, adequate cardiac function, and an ECOG performance status of 0 or 1.

Investigators are also assessing the safety and efficacy of zanidatamab plus standard-of-care therapy vs standard therapy alone in patients with first-line advanced or metastatic HER2-positive BTC as part of the open-label phase 3 HERIZON-BTC-302 trial (NCT06282575). The trial is currently open for enrollment and intended to confirm the clinical utility of zanidatamab for those with BTC.

References

1. Zanidatamab granted priority review for HER2-positive metastatic biliary tract cancer. News release. Jazz Pharmaceuticals, Inc. May 29, 2024. Accessed May 30, 2024. https://tinyurl.com/3eshw7n2
2. Harding JJ, Fan J, Oh DY, 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