Multicenter phase II trial of trastuzumab deruxtecan for HER2-positive unresectable or recurrent biliary tract cancer: HERB trial

Trastuzumab deruxtecan (DS-8201) is an antibody-drug conjugate composed of a humanized monoclonal anti-HER2 antibody, a cleavable tetrapeptide-based linker and a potent topoisomerase I inhibitor. The drug's efficacy has been proven in HER2-positive breast and gastric cancers. The rate of HER2 positivity in biliary tract cancer (BTC) has been reported to be 5-20%, and case reports and clinical trials have suggested that HER2 inhibitors might be active in HER2-positive BTC. Here we describe the rationale and design of the phase II HERB trial that will evaluate the efficacy and safety of trastuzumab deruxtecan in patients with HER2-expressing unresectable or recurrent BTC. The primary end point will be the centrally assessed objective response rate in HER2-positive patients.Trastuzumab deruxtecan (DS-8201) is a new drug against HER2, a receptor on cell membranes that has sensitivity to targeted inhibitors. The drug’s efficacy has been proven in HER2-positive breast and gastric cancers. Some studies have suggested that HER2 inhibitors might be active in HER2-positive biliary tract cancers. This article describes the design of a new clinical trial. The HERB trial is designed to evaluate the efficacy and safety of trastuzumab deruxtecan in patients with HER2-expressing biliary tract cancers. Clinical trial registration: JMA-IIA00423.