HER2-Selective Tyrosine Kinase Inhibitor, Zongertinib (BI 1810631), in Patients With Advanced/Metastatic Solid Tumors With HER2 Alterations: A Phase Ia Dose-Escalation Study

作者：John V. Heymach, Frans L. Opdam, Minal Barve, Hai‐Yan Tu, Yi‐Long Wu, David Berz, L Schröter, Yanick Botilde, Behbood Sadrolhefazi, Josep Serra, Kiyotaka Yoh, Noboru Yamamoto · 发表于：Journal of Clinical Oncology · 年份：2025 · DOI：10.1200/jco-24-01727 · 被引用次数：48 · 研究领域：Lung Cancer Treatments and Mutations、HER2/EGFR in Cancer Research、Lung Cancer Research Studies

PURPOSE: Human epidermal growth factor receptor 2 (HER2) alterations occur in many solid cancers, including non-small cell lung cancer (NSCLC). Beamion LUNG-1 (ClinicalTrials.gov identifier: NCT04886804) is assessing the safety/efficacy of zongertinib (BI 1810631), a novel HER2-selective tyrosine kinase inhibitor that spares epidermal growth factor receptor, in patients with HER2-altered solid tumors. MATERIALS AND METHODS: Beamion LUNG-1 is an ongoing multicenter, multicohort phase Ia/Ib trial. Phase Ia assessed zongertinib administered twice a day (15-150 mg) or once daily (60-360 mg) in pretreated patients with various tumors, including NSCLC. Primary end points were maximum tolerated dose (MTD) and dose-limiting toxicities (DLTs); tumor response was a secondary end point. RESULTS: As of May 23, 2024, 105 patients were treated. Two DLTs occurred during the MTD evaluation period; MTD was not reached (NR). The recommended doses for expansion were 120 mg once daily and 240 mg once daily. Treatment-related adverse events (TRAEs; any/grade ≥3) occurred in 82%/10% of patients. The most common TRAEs (any/grade ≥3) included diarrhea (50%/1%), rash (16%/2%), anemia (10%/0%), decreased appetite (10%/1%), and increased alanine transaminase (10%/4%). The confirmed investigator-assessed overall response rate (ORR) across all doses/tumors was 30% (95% CI, 23 to 40); median duration of response was 12.7 months (95% CI, 6.9 to NR). In 54 patients with NSCLC, confirmed ORR was 35% (95% CI,...