Jazz Pharmaceuticals announced that the U.S. Food and Drug Administration (FDA) has granted accelerated approval to Ziihera® (zanidatamab-hrii) for the treatment of adults with previously treated, unresectable or metastatic HER2-positive (IHC 3+) biliary tract cancer (BTC). This approval marks a significant advancement in the treatment landscape for BTC, a disease with historically poor prognosis and limited therapeutic options. Ziihera is the first and only dual HER2-targeted bispecific antibody approved for this indication in the U.S., offering a new chemotherapy-free option for these patients.
The FDA's decision was based on data from the HERIZON-BTC-01 trial, a Phase 2b study that evaluated zanidatamab as a single agent in patients with HER2-positive BTC who had previously received gemcitabine-containing therapy. The trial demonstrated a 52% objective response rate (ORR) with a 95% confidence interval (CI) of 39-65%, and a Kaplan Meier (KM) estimated median duration of response (DOR) of 14.9 months with a 95% CI of 7.4 months to not estimable, as determined by independent central review (ICR) according to RECIST v1.1.
Clinical Efficacy and Safety
The HERIZON-BTC-01 trial enrolled 62 patients with HER2-positive BTC. Patients had to have HER2 status confirmed with tissue samples by a central lab. The study's primary endpoint was confirmed ORR by ICR. Key secondary endpoints included duration of response and safety outcomes.
According to Dr. James Harding, associate attending, Gastrointestinal Oncology and Early Drug Development Services, at Memorial Sloan Kettering Cancer Center, "Zanidatamab has demonstrated antitumor activity and is now a new option for patients with HER2-positive biliary tract cancer. I look forward to continued and successful drug development for patients with biliary tract cancer."
In terms of safety, serious adverse reactions occurred in 53% of patients who received Ziihera in the HERIZON-BTC-01 trial. The most common adverse reactions (≥ 20%) were diarrhea, infusion-related reaction, abdominal pain, and fatigue. A fatal adverse reaction of hepatic failure occurred in one patient. The prescribing information for Ziihera includes a Boxed Warning for embryo-fetal toxicity, advising patients of the risk and need for effective contraception.
Ongoing Confirmatory Trial
Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial. The confirmatory, global, randomized Phase 3 trial HERIZON-BTC-302 (NCT06282575) is currently underway. This trial is 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.
About Zanidatamab
Ziihera (zanidatamab-hrii) is a bispecific HER2-directed antibody that binds to two distinct extracellular domains of HER2, leading to receptor internalization and reduced tumor cell surface expression. It also induces complement-dependent cytotoxicity (CDC), antibody-dependent cellular cytotoxicity (ADCC), and antibody-dependent cellular phagocytosis (ADCP), resulting in tumor growth inhibition and cell death.
Zanidatamab is also being investigated in Phase 3 trials for gastroesophageal adenocarcinomas (GEAs) and metastatic breast cancer (mBC).
