2. Academic Validation
  3. Sevabertinib, a Reversible HER2 Inhibitor with Activity in Lung Cancer

Sevabertinib, a Reversible HER2 Inhibitor with Activity in Lung Cancer

  • Cancer Discov. 2025 Oct 15. doi: 10.1158/2159-8290.CD-25-0605.
Franziska Siegel 1,  Stephan Siegel 2,  Kristýna Kotýnková 3,  Gizem Karsli Uzunbas 3,  Daniel Korr 4,  Haruna Tomono 3,  Sawyer Andersen 3,  Daniel Denney 3,  Markus Berger 5,  Volker K Schulze 2,  Timothy A Lewis 6,  Bethany Kaplan 3,  Sven Golfier 4,  Jérémie Mortier 5,  Roman C Hillig 4,  Ulf Boemer 7,  Kirstin Petersen 5,  Knut Eis 5,  Sybil Williams 8,  Dominik Rüttinger 5,  Andrew D Cherniack 3,  Herbert H Loong 9,  Koichi Goto 10,  Paolo Grassi 11,  Matthew Meyerson 12,  Heidi Greulich 3
Affiliations

Affiliations

  • 1 Bayer AG, Germany.
  • 2 Bayer (Germany), Berlin, Germany.
  • 3 Broad Institute, Cambridge, MA, United States.
  • 4 Nuvisan ICB GmbH, Berlin, Germany.
  • 5 Bayer AG, Berlin, Germany.
  • 6 Broad Institute, Cambridge, United States.
  • 7 Nuvisan (Germany), Germany.
  • 8 Bayer HealthCare Pharmaceuticals, Cambridge, Massachusetts, United States.
  • 9 Chinese University of Hong Kong, Hong Kong SAR, Hong Kong.
  • 10 National Cancer Center Hospital East, Kashiwa, Chiba, Japan.
  • 11 Bayer (Italy), Milan, Italy.
  • 12 Dana-Farber Cancer Institute, Boston, MA, United States.
PMID: 41090369 DOI: 10.1158/2159-8290.CD-25-0605
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.

Figures
Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-164718
    99.90%, EGFR-HER2 Inhibitor