Jazz Pharmaceuticals' Ziihera (zanidatamab-hrii) has been included as a category 2A treatment option in the National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines in Oncology for biliary tract cancers (BTC). This update follows the FDA's accelerated approval of Ziihera in November 2024 for adults with previously treated, unresectable or metastatic HER2-positive (IHC 3+) BTC, marking a significant advancement in the treatment landscape for this challenging disease. Ziihera is now commercially available in the United States.
Clinical Basis for Approval
The FDA's accelerated approval was based on data from the Phase 2b HERIZON-BTC-01 trial. The trial demonstrated a 52% objective response rate (ORR) and a median duration of response (DOR) of 14.9 months as determined by independent central review (ICR) in patients with HER2-positive BTC. These results, presented at the American Society of Clinical Oncology (ASCO) Annual Meeting 2023 and published in The Lancet Oncology, highlight the clinical benefit of zanidatamab in this patient population.
Rob Iannone, MD, MSCE, EVP, global head of research and development, and chief medical officer of Jazz Pharmaceuticals, stated, "The addition of Ziihera to the NCCN Guidelines in Oncology reaffirms the importance of this advancement in treating BTC and supports our commitment to ensuring that HER2-positive BTC patients, through their health care professionals, can access this important new therapeutic option. Ziihera is the first and only dual HER2-targeted bispecific antibody and chemotherapy-free treatment for patients living with BTC – a disease with a poor prognosis and limited treatment options."
HERIZON-BTC-01 Trial Details
The HERIZON-BTC-01 trial was an open-label, global Phase 2b study that enrolled 87 patients with HER2-amplified, locally advanced unresectable or metastatic BTC. The trial evaluated zanidatamab (20 mg/kg IV every 2 weeks) in patients who had received prior gemcitabine-containing therapy. Patients with prior HER2-targeted therapy use were excluded from the trial. The primary endpoint was ORR by independent central review (ICR) in Cohort 1, with secondary endpoints including other efficacy and safety outcomes.
Ongoing Confirmatory Trial
Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial. The Phase 3 HERIZON-BTC-302 trial (NCT06282575) is currently underway, evaluating zanidatamab in combination with standard-of-care therapy versus standard-of-care therapy alone in the first-line setting for patients with HER2-positive BTC.
Safety Profile
The safety profile of Ziihera was demonstrated in 80 patients in the HERIZON-BTC-01 trial. Serious adverse reactions occurred in 53% of patients who received Ziihera. The most common adverse reactions (≥ 20%) were diarrhea, infusion-related reaction, abdominal pain, and fatigue. A Boxed Warning for embryo-fetal toxicity advises patients of the risk and need for effective contraception.
Biliary Tract Cancer Landscape
Biliary tract cancers, including gallbladder cancer and intrahepatic and extrahepatic cholangiocarcinoma, account for less than 1% of all adult cancers globally and are often associated with a poor prognosis. Approximately 12,000 people are diagnosed with HER2+ BTC annually across the U.S., Europe, and Japan.
