First-Line Zongertinib in Advanced HER2 -Mutant Non–Small-Cell Lung Cancer

作者：John V. Heymach, Noboru Yamamoto, Nicolas Girard, G Ruiter, Egbert F. Smit, David Planchard, Ernest Nadal, Yi-Long Wu, Jon Zugazagoitia, Hai-Yan Tu, Christina S. Baik, Kiyotaka Yoh, Ross A. Soo, Y W Zhao, Joshua K. Sabari, Martin Wermke, Matthias Scheffler, Myung-Ju Ahn, Kristie Fernamberg, L. Schroeter, Behbood Sadrolhefazi, Claus Thamer, Sabina Eigenbrod-Giese, Sanjay Popat · 发表于：New England Journal of Medicine · 年份：2026 · DOI：10.1056/nejmoa2516969 · 被引用次数：13 · 研究领域：Lung Cancer Treatments and Mutations、Lung Cancer Research Studies、HER2/EGFR in Cancer Research

BackgroundUntil recently, no first-line targeted treatment options were available for patients with human epidermal growth factor receptor 2 (HER2)–mutant non–small-cell lung cancer (NSCLC). Zongertinib is an oral, irreversible tyrosine kinase inhibitor that selectively inhibits HER2 while sparing wild-type epidermal growth factor receptor (EGFR), thereby minimizing associated toxic effects. MethodsWe conducted a phase 1a–1b, multicohort trial to assess zongertinib in patients with advanced or metastatic nonsquamous HER2-mutant NSCLC. Here, we evaluated zongertinib at a dose of 120 mg once daily in patients who had not previously received treatment (cohort 2). The primary end point was objective response as assessed by blinded independent central review. Secondary end points included duration of response and progression-free survival. In addition, zongertinib was evaluated in patients with active brain metastases (exploratory cohort 4). Research Summary First-Line Zongertinib in Advanced HER2-Mutant Non–Small-Cell Lung Cancer ResultsIn cohort 2, a total of 74 previously untreated patients received zongertinib at a dose of 120 mg. As of August 21, 2025, the percentage of patients with a confirmed objective response was 76% (95% confidence interval [CI], 65 to 84); the median duration of response was 15.2 months (95% CI, 9.8 to not evaluable), and the median progression-free survival was 14.4 months (95% CI, 11.1 to not evaluable). Adverse events of any grade occurred in 73 pat...