Jazz Pharmaceuticals has announced the completion of its rolling submission of a Biologics License Application (BLA) to the U.S. Food and Drug Administration (FDA) for zanidatamab. The company is seeking accelerated approval for the HER2-targeted bispecific antibody as a treatment for previously-treated, unresectable, locally advanced, or metastatic HER2-positive biliary tract cancer (BTC). If approved, zanidatamab would be the first HER2-targeted treatment specifically approved for BTC in the U.S.
The BLA submission is based on data from the Phase 2b HERIZON-BTC-01 trial, which evaluated zanidatamab in patients with previously treated HER2-positive BTC. The trial's primary endpoint was confirmed objective response rate (cORR) by independent central review (ICR) in Cohort 1. Data from the 80 patients enrolled in Cohort 1, as of October 10, 2022, demonstrated a cORR of 41.3% [95% confidence interval (CI): 30.4, 52.8] with a Kaplan Meier (KM) estimated median duration of response (DOR) of 12.9 months [95% CI: 6.0-not estimable] by ICR. In comparison, historical response rates for second-line standard-of-care chemotherapy in patients with BTC are reported to be 5 to 15%.
The KM estimated median progression-free survival (PFS) was 5.5 months [95% CI: 3.7, 7.2] with a range of 0.3 to 18.5 months. Zanidatamab exhibited a manageable safety profile, with only 2.3% of patients experiencing adverse events (AEs) leading to treatment discontinuation. The most common AEs were diarrhea and infusion-related reactions, which were predominately low-grade, reversible, and manageable with routine supportive care.
Ongoing Phase 3 Trial
The HERIZON-BTC-302 Phase 3 trial (NCT06282575) has recently been initiated to further evaluate zanidatamab in first-line advanced or metastatic HER2-positive BTC. This global, open-label, randomized trial will assess the efficacy and safety of zanidatamab in combination with standard-of-care therapy against standard-of-care therapy alone. The primary objective is to compare the efficacy of zanidatamab and chemotherapy (cisplatin plus gemcitabine) with or without the addition of a programmed death protein 1/ligand 1 (PD-1/L-1) inhibitor versus chemotherapy with or without a PD-1/L1 inhibitor in patients. HERIZON-BTC-302 is proposed as the confirmatory trial for zanidatamab in BTC.
About Zanidatamab
Zanidatamab is an investigational bispecific antibody that can simultaneously bind two non-overlapping epitopes of HER2, known as biparatopic binding. This unique design and increased binding 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. Zanidatamab is being developed in multiple clinical trials as a targeted treatment option for patients with solid tumors that express HER2. Zanidatamab is being developed by Jazz and BeiGene, Ltd. (BeiGene) under license agreements from Zymeworks, which first developed the molecule.
Biliary Tract Cancer (BTC) Overview
Biliary tract cancer (BTC), including gallbladder cancer and intrahepatic and extrahepatic cholangiocarcinoma, accounts for less than 1% of all adult cancers and is often associated with a poor prognosis. The human epidermal growth factor receptor 2 (HER2) is a well-validated target for antitumor therapy in other cancers. Across the U.S., Europe, and Japan, approximately 12,000 people are diagnosed with BTC annually, and most patients (> 65%) are diagnosed with tumors that cannot be removed surgically.
