FDA granted accelerated approval of Ziihera (zanidatamab-hrii) for injection to treat  unresectable or metastatic HER2-positive (IHC 3+) biliary tract cancer

Ziihera was approved under accelerated approval based on a 52% objective response rate (ORR) and a median duration of response (DOR) of 14.9 months as determined by independent central review (ICR). Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial. The Phase III  HERIZON-BTC-302 confirmatory trial is ongoing to evaluate 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. 

BTC is a devastating disease with a poor prognosis and five-year survival rates under five percent in the metastatic setting. Patients with unresectable or metastatic HER2-positive BTC have had a high unmet need with limited treatment options and few approved therapies," said Rob Iannone, M.D., M.S.C.E., executive vice president, global head of research and development, and chief medical officer of Jazz Pharmaceuticals. "The approval of Ziihera, which previously received Breakthrough Therapy Designation from the FDA for this indication, is an important advance and offers the first and only dual HER2-targeted bispecific antibody and chemotherapy-free treatment for patients living with BTC. We look forward to advancing research of zanidatamab in BTC and other HER2-expressing solid tumors, with the goal of improving outcomes for more people diagnosed with these difficult-to-treat HER2-positive cancers."

The FDA approval of Ziihera is based on compelling data from the HERIZON-BTC-01 trial, which included the evaluation of zanidatamab as a single agent in previously treated HER2-positive (as determined by Roche Diagnostic's PATHWAY anti-HER-2/neu (4B5) Rabbit Monoclonal Primary Antibody companion diagnostic).BTC and is the largest Phase IIb clinical trial to date specifically for this patient population. The trial achieved its primary endpoint of confirmed objective response rate (cORR) by independent central review (ICR) and results were presented at the American Society of Clinical Oncology (ASCO) Annual Meeting 2023, published in The Lancet Oncology, and included in the 2023 Best of ASCO program. Longer follow-up data showing improvement upon previously reported DOR were reported at the ASCO Annual Meeting 2024.

Citation: Volume 24, Issue 7p772-782 July 2023 "Zanidatamab for HER2-amplified, unresectable, locally advanced or metastatic biliary tract cancer (HERIZON-BTC-01): a multicentre, single-arm, phase IIb study"- James J Harding, MD^,∙ Jia Fan, MD ∙, Do-Youn Oh, MD, ∙ Hye Jin Choi, MD, ∙ Jin Won Kim, MD, ∙ Heung-Moon Chang, MD∙ et al. The Lancet Oncology.