ArticleThe Journal of biological chemistry
Discovery of amivantamab (JNJ-61186372), a bispecific antibody targeting EGFR and MET.
Article in The Journal of biological chemistry. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 107 papers, 2 of them syntheses that pooled it.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
107 citing papers in PubMed, 2 syntheses or guidelines pooled it, 157 citations in OpenAlex.
- Dual-target immunotherapies in NSCLC: a systematic review and meta-analysis of randomized clinical trials.Frontiers in immunology · 2025Pooled it
- Therapeutic exploration of uncommon EGFR exon 20 insertion mutations in advanced non-small cell lung cancer: breaking through brambles and thorns.Journal of cancer research and clinical oncology · 2022Pooled it
- Poziotinib for EGFR exon 20-insertion NSCLC: Clinical efficacy of the phase 2 ZENITH trial and differential impact of EGFR exon 20 insertion location on sensitivity.Nature communications · 2025Trial
- Deciphering resistance mechanisms in cancer: final report of MATCH-R study with a focus on molecular drivers and PDX development.Molecular cancer · 2024Trial
- Review
- Functional Characteristics Derived from the Structural Design of Bispecific Antibodies.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Tyrosine Kinase Inhibitors, Antibody-Drug Conjugates, and Bispecific Antibodies in Oncogene-Driven Non-Small-Cell Lung Cancer: Evolving Roles in Treatment Sequencing and Resistance Management.International journal of molecular sciences · 2026Review
- Therapeutic Targeting of VEGFR-2, PD-L1, and EGFR-MET Pathways in Non-Small Cell Lung Cancer: Clinical Progress with Ramucirumab, Atezolizumab, and Amivantamab.Journal of clinical medicine · 2026Review
- A MET-Targeted Variable New Antigen Receptor (VNAR) Theranostic for Non-Small Cell Lung Cancer.bioRxiv : the preprint server for biology · 2026Article
- Emerging Role of Bispecific Antibodies in Precision Medicine, Cancer and Modern Therapeutics.Current oncology reports · 2026Review
- B7-H3-mediated cis-inhibition of EGFR by a tumor-selective bispecific antibody enhances anti-tumor efficacy and minimizes toxicities.Nature communications · 2026Article
- DNA-programmed bispecific peptide assemblies for delivering cytotoxic payload to cells expressing EGFR and MET receptors.RSC chemical biology · 2026Article
- Review
- A New Paradigm of Bispecific Antibodies in Clinical Management of Gastrointestinal Cancers.Oncology research · 2026Review
- MET Enhances Amivantamab Binding to EGFR and Antibody-Dependent Cellular Toxicity.Cancer science · 2026Article
- Papulopustular eruptions associated with EGFR-pathway-related targeted therapies: clinical spectrum, evidence boundaries, folliculocentric inflammation, and management considerations.Frontiers in oncology · 2026Review
- Global research progress in antibody-drug conjugates for solid tumors: Bibliometrics and visualized analysis.Human vaccines & immunotherapeutics · 2025Review
- Precision navigation through the labyrinth: overcoming EGFR resistance in non-Small cell lung cancer.Annals of medicine · 2025Review
- Technological advancements in antibody-based therapeutics for treatment of diseases.Journal of biomedical science · 2025Review
- Building a dynamic model for EGFR-family dimerization using quantitative, live-cell fluorescence methods.Biophysical journal · 2025Review
47 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
A bispecific antibody (BsAb) targeting the epidermal growth factor receptor (EGFR) and mesenchymal-epithelial transition factor (MET) pathways represents a novel approach to overcome resistance to targeted therapies in patients with non-small cell lung cancer. In this study, we sequentially screened a panel of BsAbs in a combinatorial approach to select the optimal bispecific molecule. The BsAbs were derived from different EGFR and MET parental monoclonal antibodies. Initially, molecules were screened for EGFR and MET binding on tumor cell lines and lack of agonistic activity toward MET. Hits were identified and further screened based on their potential to induce untoward cell proliferation and cross-phosphorylation of EGFR by MET via receptor colocalization in the absence of ligand. After the final step, we selected the EGFR and MET arms for the lead BsAb and added low fucose Fc engineering to generate amivantamab (JNJ-61186372). The crystal structure of the anti-MET Fab of amivantamab bound to MET was solved, and the interaction between the two molecules in atomic details was elucidated. Amivantamab antagonized the hepatocyte growth factor (HGF)-induced signaling by binding to MET Sema domain and thereby blocking HGF β-chain-Sema engagement. The amivantamab EGFR epitope was mapped to EGFR domain III and residues K443, K465, I467, and S468. Furthermore, amivantamab showed superior antitumor activity over small molecule EGFR and MET inhibitors in the HCC827-HGF in vivo model. Based on its unique mode of action, amivantamab may provide benefit to patients with malignancies associated with aberrant EGFR and MET signaling.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.