Amivantamab, an Epidermal Growth Factor Receptor (EGFR) and Mesenchymal-epithelial Transition Factor (MET) Bispecific Antibody, Designed to Enable Multiple Mechanisms of Action and Broad Clinical Applications
- PMID: 36481319
- DOI: 10.1016/j.cllc.2022.11.004
Amivantamab, an Epidermal Growth Factor Receptor (EGFR) and Mesenchymal-epithelial Transition Factor (MET) Bispecific Antibody, Designed to Enable Multiple Mechanisms of Action and Broad Clinical Applications
Abstract
Substantial therapeutic advancements have been made in identifying and treating activating mutations in advanced non-small cell lung cancer (NSCLC); however, resistance to epidermal growth factor receptor (EGFR) and mesenchymal-epithelial transition factor (MET) inhibitors remains common with current targeted therapies. Amivantamab, a fully human bispecific antibody targeting EGFR and MET, is approved in the United States and other countries for the treatment of patients with advanced NSCLC with EGFR exon 20 insertion mutations, for whom disease has progressed on or after platinum-based chemotherapy. Preliminary efficacy and safety have also been demonstrated in patients with common EGFR- or MET-mutated NSCLC. Amivantamab employs 3 distinct potential mechanisms of action (MOAs) including ligand blocking, receptor degradation, and immune cell-directing activity, such as antibody-dependent cellular cytotoxicity and trogocytosis. Notably, efficacy with amivantamab does not require all 3 MOAs to occur simultaneously, broadening applicability by using diverse antitumor mechanisms. This review focuses on the molecular characteristics of amivantamab and its unique MOAs leading to in vitro and in vivo efficacy and safety in preclinical and clinical studies.
Keywords: Exon 20 insertions; Immune cell-directing activity; Ligand blocking; Resistance pathways; Targeted therapy.
Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.
Conflict of interest statement
Disclosures Allison Simi,mruthi Vijayaraghavan, and Sheri Moores are employees of Janssen Pharmaceuticals. Grants or contracts: Alexander Spira: LAM Therapeutics, Roche, AstraZeneca, Boehringer Ingelheim, Astellas Pharma, MedImmune, Novartis, Newlink Genetics, Incyte, AbbVie, Ignyta, Trovagene, Takeda, Macrogenics, CytomX Therapeutics, Astex Pharmaceuticals, Bristol Myers Squibb, Loxo, Arch Therapeutics, Gritstone, Plexxikon, Amgen, Daiichi Sankyo, ADCT, Janssen Oncology, Mirati Therapeutics, Rubius, Synthekine, Mersana, Blueprint Medicines. Byoung Chul Cho: Novartis, Bayer, AstraZeneca, MOGAM Institute, Dong-A ST, Champions Oncology, Janssen, Yuhan, Ono, Dizal Pharma, MSD, AbbVie, Medpacto, GI Innovation, Eli Lilly, Blueprint Medicines, Interpark Bio Convergence Corporation. Joshua Sabari: Janssen, Loxo/Eli Lilly, Mirati, Regeneron. Royalties or licenses: Byoung Chul Cho: Champions Oncology. Consulting fees: Alexander Spira: Incyte, Amgen, Novartis, Mirati Therapeutics, Gritstone Oncology, Jazz Pharmaceuticals, Takeda, Janssen Research & Development, Mersana, Gritstone Bio, Daiichi Sankyo/AstraZeneca, Array BioPharma, AstraZeneca/MedImmune, Merck, Bristol Myers Squibb, Blueprint Medicines. Byoung Chul Cho: Novartis, AstraZeneca, Boehringer Ingelheim, Roche, Bristol Myers Squibb, Ono, Yuhan, Pfizer, Eli Lilly, Janssen, Takeda, MSD, Medpacto, Blueprint Medicines. Joshua Sabari: AstraZeneca, Mirati, Navire. Payment or honoraria: Alexander Spira: CytomX Therapeutics, AstraZeneca/MedImmune, Merck, Takeda, Amgen, Janssen Oncology, Novartis, Bristol Myers Squibb, Bayer. Patents planned, issued, or pending: Smruthi Vijayaraghavan, Sheri Moores. Participation on a Data Safety Monitoring Board or Advisory Board: Byoung Chul Cho: KANAPH Therapeutic, Inc., Bridgebio Therapeutics, Cyrus Therapeutics, Guardant Health, Joseah BIO. Joshua Sabari: AstraZeneca, Genentech, Janssen, Pfizer, Pharma Mar, Regeneron, Sanofi Genzyme, Takeda. Leadership or fiduciary role: Byoung Chul Cho: Gencurix, Inc., Interpark Bio Convergence Corp. Stock or stock options: Alexander Spira: Eli Lilly. Byoung Chul Cho: TheraCanVac, Inc., Gencruix, Inc., Bridgebio Therapeutics, KANAPH Therapeutic, Inc., Cyrus Therapeutics, Interpark Bio Convergence Corp. Smruthi Vijayaraghavan: Johnson & Johnson. Sheri Moores: Johnson & Johnson. Other financial or non-financial interests: Byoung Chul Cho: DAAN Biotherapeutics.
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