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| Primary information |
|---|
| ID | 16152 |
| Therapeutic ID | Th1683 |
| Protein Name | Amivantamab |
| Sequence | >Th1683_Amivantamab
QVQLVQSGAEVAKPGTSVKLSCKASGYTFTDYWMQWVKQRPGQGLEWIGTIYPGDGDTGYAQKFQGKATLTADKSSKTVYMHLSSLASEDSAVYYCARGDYYGSNSLDYWGQGTSVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK
|
| Molecular Weight | 148000 |
| Chemical Formula | NA |
| Isoelectric Point | NA |
| Hydrophobicity | NA |
| Melting point | NA |
| Half-life | The terminal half life of amivantamab-vmjw is 11.3 ± 4.53 days.[L34193] |
| Description | Amivantamab, also known as JNJ-61186372, is an anti-EGFR-MET bispecific antibody, derived from Chinese hamster ovary cells, approved for the treatment of adult patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) exon 20 insertion mutations, as detected by an FDA-approved test, whose disease has progressed on or after platinum-based chemotherapy.[A235103,L34193] Patients with NSCLC often develop resistance to drugs that target EGFR and MET individually, so amivantamab was developed to attack both targets, reducing the chance of resistance developing.[A235103,A235118] Amivantamab was found to be more effective than the EGFR inhibitor [erlotinib] or the MET inhibitor [crizotinib] _in vivo_.[A235103,A235123] Patients with NSCLC with exon 20 insertion mutations in EGFR do not respond to tyrosine kinase inhibitors, and were generally treated with platinum-based therapy.[A235133] Amivantamab was granted FDA approval on 21 May 2021.[L34193] |
| Indication/Disease | Amivantamab is indicated in the treatment of adult patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) exon 20 insertion mutations, whose disease has progressed on or after platinum-based chemotherapy.[L34193] |
| Pharmacodynamics | Amivantamab is an EGF and MET receptor targeted antibody indicated in the treatment of non-small cell lung cancer with an EGFR 20 exon insertion mutation.[L34193] It has a long duration of action, as activity can be detected up to 8 weeks after treatment.[A235103] Patients should be counselled regarding the risk of infusion-related reactions, interstitial lung disease and pneumonitis, skin reactions, ocular toxicity, and paronychia.[L34193] Patients should not take amivantamab if they are pregnant or breastfeeding.[L34193] |
| Mechanism of Action | Mesenchymal-epithelial transition factor (MET) is a receptor with tyrosine kinase activity expressed on epithelial cells that, upon signalling, dimerizes and activates downstream pathways that signal cell division.[A235103,A235128] The Epidermal Growth Factor Receptor (EGFR) is a transmembrane protein with tyrosine kinase activity that can further activate downstream pathways that signal cell division, survival, and angiogenesis.[A235103,A235128] Patients with NSCLC with exon 20 insertion mutations in EGFR do not respond to tyrosine kinase inhibitors, and are generally treated with platinum-based therapy.[A235133] Exon 20 insertion mutations in EGFR also lead to conformational changes that activate EGFR.[A235138] Amivantamab targets both EGFR and MET, preventing ligands from binding to the receptors, blocking signalling, marking the cancerous cells for antibody-dependant cellular cytotoxicity by natural killer cells, and allowing macrophages to perform trogocytosis.[L34193] Amivantamab's binding to the EGFR H epitope shares some of the same amino acids that [cetuximab] binds to.[A235103] Amivantamab's binding to the alpha chain of MET stabilizes the Sema domain loop 1 to 2 in a position 6 Angstroms away from the position it would be in under normal binding, preventing its interaction with the hepatocyte growth factor's (HGF) beta chain.[A235103] Another smaller conformational change in the MET Sema domain loop 1 to 3 also contributes to preventing the interaction of the MET Sema domain with HGF's beta chain.[A235103] HGF is no longer able to bind to MET, preventing downstream signalling.[A235103] Amivantamab's Fc portion contains 90% less fucose than normal antibodies, allowing for increased binding to the FcRIIIa region.[A235128] Binding of the Fc portion of Amivantamab signals the complement system and innate immune system to target the bound cells for complement-dependent cytotoxicity, antibody-dependent cell-mediated cytotoxicity, and antibody-dependent cellular phagocytosis.[A235128] Binding of amivantamab to the Fc receptor also leads to and increase in levels of IFN.[A235138] Amivantamab also significantly downregulates the expression of EGFR and MET on NSCLC cell surfaces, further reducing downstream signalling.[A235138,A235108] EGFR and MET on the cell surface are internalized, and possibly degrading by fusing endosomes with lysosomes.[A235138] Alternatively, EGFR and MET are the subjects of monocyte-dependent trogocytosis.[A235108] Trogocytosis allows monocytes to internalize and break down EGFR and MET from the NSCLC cells without cytotoxicity, downmodulating EGFR and MET receptors.[A235108] |
| Toxicity | Data regarding overdoses of amivantamab are not readily available.[L34193] Patients experiencing an overdose should be treated with symptomatic and supportive measures. |
| Metabolism | Antibodies are expected to be metabolized to oligopeptides and amino acids.[A40006] |
| Absorption | NA |
| The mean volume of distribution of amivantamab-vmjw is 5.13 ±1.78 L.[L34193] |
| Clearance | The mean clearance of amivantamab-vmjw is 360 ± 144 mL/day.[L34193] |
| Categories | Proteins |
| Patents Number | NA |
| Date of Issue | NA |
| Date of Expiry | NA |
| Drug Interaction | NA |
| Target | Epidermal growth factor receptor,Hepatocyte growth factor receptor,Low affinity immunoglobulin gamma Fc region receptor III-A |
| Brand Name | NA |
| Company | NA |
| Brand Description | NA |
| Prescribed For | NA |
| Chemical Name | NA |
| Formulation | NA |
| Physical Appearance | NA |
| Route of Administration | NA |
| Recommended Dosage | NA |
| Contraindication | NA |
| Side Effects | NA |
| Useful Link 1 | Link |
| Useful Link 2 | NA |
| Remarks | NA |