Zanidatamab in previously-treated HER2-positive (HER2+) biliary tract cancer (BTC): Overall survival (OS) and longer follow-up from the phase 2b HERIZON-BTC-01 study.

作者：Shubham Pant, Jia Fan, Do‐Youn Oh, Hye Jin Choi, Jin Won Kim, Heung-Moon Chang, Lequn Bao, Hui‐Chuan Sun, Teresa Macarulla, Feng Xie, Jean‐Philippe Metges, Ying Jieer, John Bridgewater, Mohamedtaki Abdulaziz Tejani, Emerson Yu-sheng Chen, Harpreet Wasan, Michel Ducreux, Ian Zhao, Phillip M. Garfin, James J. Harding · 发表于：Journal of Clinical Oncology · 年份：2024 · DOI：10.1200/jco.2024.42.16_suppl.4091 · 被引用次数：21 · 研究领域：Cholangiocarcinoma and Gallbladder Cancer Studies、Peptidase Inhibition and Analysis、Gastric Cancer Management and Outcomes

4091 Background: For patients with BTC that has progressed after first-line therapy, prognosis is poor with a median OS of 6-9 months with subsequent chemotherapy. Zanidatamab is a HER2-targeted bispecific antibody that binds to two non-overlapping HER2 domains and crosslinks neighboring HER2 proteins. In the primary analysis of the phase 2b HERIZON-BTC-01 trial, after a median follow-up of 12.4 months (data cutoff: October 10, 2022), zanidatamab showed encouraging antitumor activity (41% confirmed objective response rate [cORR]) with rapid and durable responses and a manageable safety profile in patients with previously treated HER2+ BTC. OS data were immature at that time. Here, we report updated analyses, including OS. Methods: HERIZON-BTC-01 (NCT04466891) is an ongoing phase 2b trial assessing zanidatamab (20 mg/kg IV Q2W) in patients with HER2/ERBB2 gene amplification and immunohistochemistry (IHC) 2+ or 3+ (Cohort 1; HER2+); or 0 or 1+ (Cohort 2) locally advanced, unresectable, or metastatic BTC (gallbladder cancer, intra/extrahepatic cholangiocarcinoma) who received prior gemcitabine-containing treatment. The primary endpoint was cORR. Select secondary endpoints included duration of response (DoR), OS, and frequency and severity of adverse events (AEs). Updated efficacy analyses include only Cohort 1; safety analyses include Cohorts 1 and 2. Results: As of the data cutoff (July 28, 2023), median (range) follow-up was 21.9 (16-34) months. In the 80 patients in Cohort 1 ...