Mobocertinib (TAK-788): A Targeted Inhibitor of<i>EGFR</i>Exon 20 Insertion Mutants in Non–Small Cell Lung Cancer
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- Francois Gonzalvez
- 1ARIAD Pharmaceuticals, Inc., Cambridge, Massachusetts, a wholly owned subsidiary of Takeda Pharmaceutical Company Limited.
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- Sylvie Vincent
- 2Millennium Pharmaceuticals, Inc., Cambridge, Massachusetts, a wholly owned subsidiary of Takeda Pharmaceutical Company Limited.
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- Theresa E. Baker
- 1ARIAD Pharmaceuticals, Inc., Cambridge, Massachusetts, a wholly owned subsidiary of Takeda Pharmaceutical Company Limited.
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- Alexandra E. Gould
- 2Millennium Pharmaceuticals, Inc., Cambridge, Massachusetts, a wholly owned subsidiary of Takeda Pharmaceutical Company Limited.
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- Shuai Li
- 3Laura and Isaac Perlmutter Cancer Center, New York University School of Medicine, NYU Langone Health, New York, New York.
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- Scott D. Wardwell
- 1ARIAD Pharmaceuticals, Inc., Cambridge, Massachusetts, a wholly owned subsidiary of Takeda Pharmaceutical Company Limited.
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- Sara Nadworny
- 1ARIAD Pharmaceuticals, Inc., Cambridge, Massachusetts, a wholly owned subsidiary of Takeda Pharmaceutical Company Limited.
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- Yaoyu Ning
- 1ARIAD Pharmaceuticals, Inc., Cambridge, Massachusetts, a wholly owned subsidiary of Takeda Pharmaceutical Company Limited.
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- Sen Zhang
- 1ARIAD Pharmaceuticals, Inc., Cambridge, Massachusetts, a wholly owned subsidiary of Takeda Pharmaceutical Company Limited.
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- Wei-Sheng Huang
- 1ARIAD Pharmaceuticals, Inc., Cambridge, Massachusetts, a wholly owned subsidiary of Takeda Pharmaceutical Company Limited.
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- Yongbo Hu
- 2Millennium Pharmaceuticals, Inc., Cambridge, Massachusetts, a wholly owned subsidiary of Takeda Pharmaceutical Company Limited.
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- Feng Li
- 1ARIAD Pharmaceuticals, Inc., Cambridge, Massachusetts, a wholly owned subsidiary of Takeda Pharmaceutical Company Limited.
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- Matthew T. Greenfield
- 1ARIAD Pharmaceuticals, Inc., Cambridge, Massachusetts, a wholly owned subsidiary of Takeda Pharmaceutical Company Limited.
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- Stephan G. Zech
- 1ARIAD Pharmaceuticals, Inc., Cambridge, Massachusetts, a wholly owned subsidiary of Takeda Pharmaceutical Company Limited.
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- Biplab Das
- 1ARIAD Pharmaceuticals, Inc., Cambridge, Massachusetts, a wholly owned subsidiary of Takeda Pharmaceutical Company Limited.
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- Narayana I. Narasimhan
- 1ARIAD Pharmaceuticals, Inc., Cambridge, Massachusetts, a wholly owned subsidiary of Takeda Pharmaceutical Company Limited.
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- Tim Clackson
- 1ARIAD Pharmaceuticals, Inc., Cambridge, Massachusetts, a wholly owned subsidiary of Takeda Pharmaceutical Company Limited.
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- David Dalgarno
- 1ARIAD Pharmaceuticals, Inc., Cambridge, Massachusetts, a wholly owned subsidiary of Takeda Pharmaceutical Company Limited.
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- William C. Shakespeare
- 1ARIAD Pharmaceuticals, Inc., Cambridge, Massachusetts, a wholly owned subsidiary of Takeda Pharmaceutical Company Limited.
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- Michael Fitzgerald
- 2Millennium Pharmaceuticals, Inc., Cambridge, Massachusetts, a wholly owned subsidiary of Takeda Pharmaceutical Company Limited.
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- Johara Chouitar
- 2Millennium Pharmaceuticals, Inc., Cambridge, Massachusetts, a wholly owned subsidiary of Takeda Pharmaceutical Company Limited.
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- Robert J. Griffin
- 2Millennium Pharmaceuticals, Inc., Cambridge, Massachusetts, a wholly owned subsidiary of Takeda Pharmaceutical Company Limited.
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- Shengwu Liu
- 4Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts.
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- Kwok-kin Wong
- 3Laura and Isaac Perlmutter Cancer Center, New York University School of Medicine, NYU Langone Health, New York, New York.
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- Xiaotian Zhu
- 1ARIAD Pharmaceuticals, Inc., Cambridge, Massachusetts, a wholly owned subsidiary of Takeda Pharmaceutical Company Limited.
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- Victor M. Rivera
- 1ARIAD Pharmaceuticals, Inc., Cambridge, Massachusetts, a wholly owned subsidiary of Takeda Pharmaceutical Company Limited.
Description
<jats:title>Abstract</jats:title><jats:sec><jats:title /><jats:p>Most EGFR exon 20 insertion (EGFRex20ins) driver mutations in non–small cell lung cancer (NSCLC) are insensitive to approved EGFR tyrosine kinase inhibitors (TKI). To address the limitations of existing therapies targeting EGFR-mutated NSCLC, mobocertinib (TAK-788), a novel irreversible EGFR TKI, was specifically designed to potently inhibit oncogenic variants containing activating EGFRex20ins mutations with selectivity over wild-type EGFR. The in vitro and in vivo activity of mobocertinib was evaluated in engineered and patient-derived models harboring diverse EGFRex20ins mutations. Mobocertinib inhibited viability of various EGFRex20ins-driven cell lines more potently than approved EGFR TKIs and demonstrated in vivo antitumor efficacy in patient-derived xenografts and murine orthotopic models. These findings support the ongoing clinical development of mobocertinib for the treatment of EGFRex20ins-mutated NSCLC.</jats:p></jats:sec><jats:sec><jats:title>Significance:</jats:title><jats:p>No oral EGFR-targeted therapies are approved for EGFR exon 20 insertion (EGFRex20ins) mutation-driven NSCLC. Mobocertinib is a novel small-molecule EGFR inhibitor specifically designed to target EGFRex20ins mutants. Preclinical data reported here support the clinical development of mobocertinib in patients with NSCLC with EGFR exon 20 insertion mutations.</jats:p><jats:p>See related commentary by Pacheco, p. 1617.</jats:p><jats:p>This article is highlighted in the In This Issue feature, p. 1601</jats:p></jats:sec>
Journal
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- Cancer Discovery
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Cancer Discovery 11 (7), 1672-1687, 2021-02-25
American Association for Cancer Research (AACR)
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Details 詳細情報について
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- CRID
- 1360294646905053056
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- ISSN
- 21598290
- 21598274
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- Data Source
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- Crossref