Sevabertinib, a Reversible HER2 Inhibitor with Activity in Lung Cancer.

IF 33.3 1区医学 Q1 ONCOLOGY

Cancer discovery Pub Date : 2025-10-15 DOI:10.1158/2159-8290.cd-25-0605

Franziska Siegel,Stephan Siegel,Kristýna Kotýnková,Gizem Karsli Uzunbas,Daniel Korr,Haruna Tomono,Sawyer Andersen,Daniel Denney,Markus Berger,Volker K Schulze,Timothy A Lewis,Bethany Kaplan,Sven Golfier,Jérémie Mortier,Roman C Hillig,Ulf Boemer,Kirstin Petersen,Knut Eis,Sybil Williams,Dominik Rüttinger,Andrew D Cherniack,Herbert H Loong,Koichi Goto,Paolo Grassi,Matthew Meyerson,Heidi Greulich

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引用次数: 0

Abstract

Exon 20 insertions of HER2, encoded by ERBB2, and other activating HER2 mutations occur in 2-4% of lung adenocarcinomas, but there are only limited therapeutic options available for these patients. Sevabertinib (BAY 2927088) is a potent and reversible dual EGFR-HER2 inhibitor that is selective with respect to wild-type EGFR. Here, we report the preclinical activity of sevabertinib in lung cancer models harboring alterations of HER2, including exon 20 insertions, point mutations, and amplification of wild-type ERBB2. We furthermore demonstrate the activity of sevabertinib in a cancer cell line dependent on a fusion of NRG1, a ligand for the HER2 family member and heterodimerization partner, HER3. Finally, we report patient responses to sevabertinib from a Phase 1/2 clinical trial, indicating potential benefit for patients with HER2-mutant lung cancer.

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西伐替尼，一种对肺癌有活性的可逆HER2抑制剂。

由ERBB2编码的HER2外显子20插入和其他激活HER2突变发生在2-4%的肺腺癌中，但这些患者只有有限的治疗选择。Sevabertinib （BAY 2927088）是一种有效且可逆的双EGFR- her2抑制剂，对野生型EGFR具有选择性。在这里，我们报告了西伐替尼在肺癌模型中具有HER2改变的临床前活性，包括外显子20插入、点突变和野生型ERBB2扩增。我们进一步证明了西伐替尼在依赖于NRG1融合的癌细胞系中的活性，NRG1是HER2家族成员和异源二聚化伴侣HER3的配体。最后，我们报告了一项1/2期临床试验中患者对西伐替尼的反应，表明对her2突变肺癌患者的潜在益处。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Cancer discovery ONCOLOGY-

CiteScore

22.90

自引率

1.40%

发文量

838

审稿时长

6-12 weeks

期刊介绍： Cancer Discovery publishes high-impact, peer-reviewed articles detailing significant advances in both research and clinical trials. Serving as a premier cancer information resource, the journal also features Review Articles, Perspectives, Commentaries, News stories, and Research Watch summaries to keep readers abreast of the latest findings in the field. Covering a wide range of topics, from laboratory research to clinical trials and epidemiologic studies, Cancer Discovery spans the entire spectrum of cancer research and medicine.