Beamion BCGC-1: phase Ib/II trial of zongertinib for advanced HER2-positive breast or gastroesophageal cancers
Year: 2025
Type: article
Study design: Study Protocol
Abstract: BACKGROUND: Overexpression and/or amplification of human epidermal growth factor receptor 2 (HER2) is a recognized oncogenic driver in metastatic breast cancer (mBC) and metastatic gastric, gastroesophageal junction, or esophageal adenocarcinomas (mGEAC). Although HER2-directed monoclonal antibodies, antibody - drug conjugates (ADCs), and tyrosine kinase inhibitors (TKIs) have revolutionized the treatment of HER2-positive tumors, additional combination regimens and/or novel agents are needed to expand sequential therapy options and improve patient outcomes - particularly following treatment with trastuzumab deruxtecan (T-DXd). Zongertinib is a novel, irreversible, HER2-selective TKI that spares EGFR. STUDY DESIGN: Here, we detail the rationale and design of Beamion BCGC-1 (NCT06324357), an international Phase Ib/II open-label trial in which patients with previously treated HER2-positive mBC or mGEAC will receive zongertinib alone or in combination. Phase Ib (dose escalation) will determine the maximum tolerated dose of zongertinib plus trastuzumab emtansine (T-DM1), T-DXd, or trastuzumab ± capecitabine, in patients with HER2-positive mBC, and plus T-DXd in patients with HER2-positive mGEAC. Phase II (dose optimization) will assess two doses of zongertinib in combination regimens, or as monotherapy, in patients with mBC or mGEAC. The trial is actively recruiting in six countries globally. CLINICAL TRIAL REGISTRATION: www.clinicaltrials.gov identifier is NCT06324357.
Source: Future Oncology
Authors: Sara Hurvitz, Matteo Simonelli, Ramón Yarza, David Berz, Shigehisa Kitano, Gianluca Del Conte, Daniel Acosta Eyzaguirre, Bernard Gaston Doger de Speville Uribe, Daniela Maier, Damijan Erzen, Sila Aykut Yazgili, Giuseppe Curigliano, Ting Deng, Min Yan, Qingyuan Zhang, Xian Wang, Izuma Nakayama, Kohei Shitara
Institutions: University of Washington, Fred Hutch Cancer Center, Humanitas University, IRCCS Humanitas Research Hospital, Japanese Foundation For Cancer Research, IRCCS Ospedale San Raffaele, Istituto di Ricovero e Cura a Carattere Scientifico San Raffaele, Vall d'Hebron Hospital Universitari, Vall d'Hebron Institute of Oncology, Boehringer Ingelheim (Germany), University of Milan, European Institute of Oncology, Tianjin Medical University Cancer Institute and Hospital, Tianjin Medical University, Zhengzhou University, Henan Cancer Hospital, Harbin Medical University, Third Affiliated Hospital of Harbin Medical University, Sir Run Run Shaw Hospital, Zhejiang University, National Cancer Center Hospital East
Language: English
Topic: HER2/EGFR in Cancer Research
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Funders: Amgen, Bristol-Myers Squibb, Eli Lilly and Company, Pfizer, AstraZeneca, Bayer, GlaxoSmithKline, Novartis, Sanofi, Gilead Sciences, Celgene, BioMarin Pharmaceutical, Merck KGaA, Taiho Pharmaceutical, Jazz Pharmaceuticals, Radius Health, Mirati Therapeutics, BeiGene, Incyte, Puma Biotechnology, MacroGenics, G1 Therapeutics, Seagen, Rakuten Medical, Eisai, Astellas Pharma, Servier, Ono Pharmaceutical, Sun Pharma, Menarini Group, Ipsen, Genentech, EMD Serono, Chugai Pharmaceutical, Eli Lilly Japan, Loxo Oncology, ImmunoMedics, Daiichi Sankyo Europe
OpenAlex ID: W4415324595