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Th1683 details
Primary information
ID16146
Therapeutic IDTh1683
Protein NameAmivantamab
Sequence>Th1683_Amivantamab QVQLVQSGAEVAKPGTSVKLSCKASGYTFTDYWMQWVKQRPGQGLEWIGTIYPGDGDTGYAQKFQGKATLTADKSSKTVYMHLSSLASEDSAVYYCARGDYYGSNSLDYWGQGTSVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK
Molecular Weight148000
Chemical FormulaNA
Isoelectric PointNA
HydrophobicityNA
Melting pointNA
Half-lifeThe terminal half life of amivantamab-vmjw is 11.3 ± 4.53 days.[L34193]
DescriptionAmivantamab, 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/DiseaseAmivantamab 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]
PharmacodynamicsAmivantamab 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 ActionMesenchymal-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]
ToxicityData regarding overdoses of amivantamab are not readily available.[L34193] Patients experiencing an overdose should be treated with symptomatic and supportive measures.
MetabolismAntibodies are expected to be metabolized to oligopeptides and amino acids.[A40006]
AbsorptionNA
The mean volume of distribution of amivantamab-vmjw is 5.13 ±1.78 L.[L34193]
ClearanceThe mean clearance of amivantamab-vmjw is 360 ± 144 mL/day.[L34193]
CategoriesAmino Acids, Peptides, and Proteins
Patents NumberNA
Date of IssueNA
Date of ExpiryNA
Drug InteractionNA
TargetEpidermal growth factor receptor,Hepatocyte growth factor receptor,Low affinity immunoglobulin gamma Fc region receptor III-A
Brand NameRybrevant
CompanyJanssen Biotech, Inc.
Brand DescriptionJanssen Biotech, Inc.
Prescribed ForIntravenous
Chemical Name350 mg/1
FormulationNone.
Physical Appearance rash, infusion related reactions, Infection of the skin surrounding the fingernails or toenails, musculoskeletal pain, shortness of breath, nausea, fatigue, fluid retention (edema), inflammation of the mouth and lips, cough, constipation, vomiting, decreased white blood cells, decreased albumin, decreased phosphate, decreased potassium, increased alkaline phosphatase, increased glucose, increased gamma-glutamyl transferase, and decreased sodium.
Route of AdministrationRybrevant is a prescription medicine used to treat adults with non-small cell lung cancer (NSCLC) that: has spread to other parts of the body (metastatic) or cannot be removed by surgery, and has a certain abnormal epidermal growth factor receptor “EGFR” gene(s) and whose disease has worsened while...
Recommended DosageRYBREVANT is indicated 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 [see DOSAGE AND ADMINISTRATION], whose disease has progressed on or after platinum-based chemotherapy.
ContraindicationNA
Side EffectsThese are not all of the possible side effects of RYBREVANT.
Useful Link 1Link
Useful Link 2Link
RemarksNA


Primary information
ID16147
Therapeutic IDTh1683
Protein NameAmivantamab
Sequence>Th1683_Amivantamab QVQLVQSGAEVAKPGTSVKLSCKASGYTFTDYWMQWVKQRPGQGLEWIGTIYPGDGDTGYAQKFQGKATLTADKSSKTVYMHLSSLASEDSAVYYCARGDYYGSNSLDYWGQGTSVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK
Molecular Weight148000
Chemical FormulaNA
Isoelectric PointNA
HydrophobicityNA
Melting pointNA
Half-lifeThe terminal half life of amivantamab-vmjw is 11.3 ± 4.53 days.[L34193]
DescriptionAmivantamab, 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/DiseaseAmivantamab 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]
PharmacodynamicsAmivantamab 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 ActionMesenchymal-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]
ToxicityData regarding overdoses of amivantamab are not readily available.[L34193] Patients experiencing an overdose should be treated with symptomatic and supportive measures.
MetabolismAntibodies are expected to be metabolized to oligopeptides and amino acids.[A40006]
AbsorptionNA
The mean volume of distribution of amivantamab-vmjw is 5.13 ±1.78 L.[L34193]
ClearanceThe mean clearance of amivantamab-vmjw is 360 ± 144 mL/day.[L34193]
CategoriesAntibodies
Patents NumberNA
Date of IssueNA
Date of ExpiryNA
Drug InteractionNA
TargetEpidermal growth factor receptor,Hepatocyte growth factor receptor,Low affinity immunoglobulin gamma Fc region receptor III-A
Brand NameNA
CompanyNA
Brand DescriptionNA
Prescribed ForNA
Chemical NameNA
FormulationNA
Physical Appearance NA
Route of AdministrationNA
Recommended DosageNA
ContraindicationNA
Side EffectsNA
Useful Link 1Link
Useful Link 2NA
RemarksNA


Primary information
ID16148
Therapeutic IDTh1683
Protein NameAmivantamab
Sequence>Th1683_Amivantamab QVQLVQSGAEVAKPGTSVKLSCKASGYTFTDYWMQWVKQRPGQGLEWIGTIYPGDGDTGYAQKFQGKATLTADKSSKTVYMHLSSLASEDSAVYYCARGDYYGSNSLDYWGQGTSVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK
Molecular Weight148000
Chemical FormulaNA
Isoelectric PointNA
HydrophobicityNA
Melting pointNA
Half-lifeThe terminal half life of amivantamab-vmjw is 11.3 ± 4.53 days.[L34193]
DescriptionAmivantamab, 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/DiseaseAmivantamab 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]
PharmacodynamicsAmivantamab 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 ActionMesenchymal-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]
ToxicityData regarding overdoses of amivantamab are not readily available.[L34193] Patients experiencing an overdose should be treated with symptomatic and supportive measures.
MetabolismAntibodies are expected to be metabolized to oligopeptides and amino acids.[A40006]
AbsorptionNA
The mean volume of distribution of amivantamab-vmjw is 5.13 ±1.78 L.[L34193]
ClearanceThe mean clearance of amivantamab-vmjw is 360 ± 144 mL/day.[L34193]
CategoriesBlood Proteins
Patents NumberNA
Date of IssueNA
Date of ExpiryNA
Drug InteractionNA
TargetEpidermal growth factor receptor,Hepatocyte growth factor receptor,Low affinity immunoglobulin gamma Fc region receptor III-A
Brand NameNA
CompanyNA
Brand DescriptionNA
Prescribed ForNA
Chemical NameNA
FormulationNA
Physical Appearance NA
Route of AdministrationNA
Recommended DosageNA
ContraindicationNA
Side EffectsNA
Useful Link 1Link
Useful Link 2NA
RemarksNA


Primary information
ID16149
Therapeutic IDTh1683
Protein NameAmivantamab
Sequence>Th1683_Amivantamab QVQLVQSGAEVAKPGTSVKLSCKASGYTFTDYWMQWVKQRPGQGLEWIGTIYPGDGDTGYAQKFQGKATLTADKSSKTVYMHLSSLASEDSAVYYCARGDYYGSNSLDYWGQGTSVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK
Molecular Weight148000
Chemical FormulaNA
Isoelectric PointNA
HydrophobicityNA
Melting pointNA
Half-lifeThe terminal half life of amivantamab-vmjw is 11.3 ± 4.53 days.[L34193]
DescriptionAmivantamab, 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/DiseaseAmivantamab 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]
PharmacodynamicsAmivantamab 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 ActionMesenchymal-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]
ToxicityData regarding overdoses of amivantamab are not readily available.[L34193] Patients experiencing an overdose should be treated with symptomatic and supportive measures.
MetabolismAntibodies are expected to be metabolized to oligopeptides and amino acids.[A40006]
AbsorptionNA
The mean volume of distribution of amivantamab-vmjw is 5.13 ±1.78 L.[L34193]
ClearanceThe mean clearance of amivantamab-vmjw is 360 ± 144 mL/day.[L34193]
CategoriesGlobulins
Patents NumberNA
Date of IssueNA
Date of ExpiryNA
Drug InteractionNA
TargetEpidermal growth factor receptor,Hepatocyte growth factor receptor,Low affinity immunoglobulin gamma Fc region receptor III-A
Brand NameNA
CompanyNA
Brand DescriptionNA
Prescribed ForNA
Chemical NameNA
FormulationNA
Physical Appearance NA
Route of AdministrationNA
Recommended DosageNA
ContraindicationNA
Side EffectsNA
Useful Link 1Link
Useful Link 2NA
RemarksNA


Primary information
ID16150
Therapeutic IDTh1683
Protein NameAmivantamab
Sequence>Th1683_Amivantamab QVQLVQSGAEVAKPGTSVKLSCKASGYTFTDYWMQWVKQRPGQGLEWIGTIYPGDGDTGYAQKFQGKATLTADKSSKTVYMHLSSLASEDSAVYYCARGDYYGSNSLDYWGQGTSVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK
Molecular Weight148000
Chemical FormulaNA
Isoelectric PointNA
HydrophobicityNA
Melting pointNA
Half-lifeThe terminal half life of amivantamab-vmjw is 11.3 ± 4.53 days.[L34193]
DescriptionAmivantamab, 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/DiseaseAmivantamab 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]
PharmacodynamicsAmivantamab 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 ActionMesenchymal-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]
ToxicityData regarding overdoses of amivantamab are not readily available.[L34193] Patients experiencing an overdose should be treated with symptomatic and supportive measures.
MetabolismAntibodies are expected to be metabolized to oligopeptides and amino acids.[A40006]
AbsorptionNA
The mean volume of distribution of amivantamab-vmjw is 5.13 ±1.78 L.[L34193]
ClearanceThe mean clearance of amivantamab-vmjw is 360 ± 144 mL/day.[L34193]
CategoriesImmunoglobulins
Patents NumberNA
Date of IssueNA
Date of ExpiryNA
Drug InteractionNA
TargetEpidermal growth factor receptor,Hepatocyte growth factor receptor,Low affinity immunoglobulin gamma Fc region receptor III-A
Brand NameNA
CompanyNA
Brand DescriptionNA
Prescribed ForNA
Chemical NameNA
FormulationNA
Physical Appearance NA
Route of AdministrationNA
Recommended DosageNA
ContraindicationNA
Side EffectsNA
Useful Link 1Link
Useful Link 2NA
RemarksNA


Primary information
ID16151
Therapeutic IDTh1683
Protein NameAmivantamab
Sequence>Th1683_Amivantamab QVQLVQSGAEVAKPGTSVKLSCKASGYTFTDYWMQWVKQRPGQGLEWIGTIYPGDGDTGYAQKFQGKATLTADKSSKTVYMHLSSLASEDSAVYYCARGDYYGSNSLDYWGQGTSVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK
Molecular Weight148000
Chemical FormulaNA
Isoelectric PointNA
HydrophobicityNA
Melting pointNA
Half-lifeThe terminal half life of amivantamab-vmjw is 11.3 ± 4.53 days.[L34193]
DescriptionAmivantamab, 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/DiseaseAmivantamab 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]
PharmacodynamicsAmivantamab 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 ActionMesenchymal-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]
ToxicityData regarding overdoses of amivantamab are not readily available.[L34193] Patients experiencing an overdose should be treated with symptomatic and supportive measures.
MetabolismAntibodies are expected to be metabolized to oligopeptides and amino acids.[A40006]
AbsorptionNA
The mean volume of distribution of amivantamab-vmjw is 5.13 ±1.78 L.[L34193]
ClearanceThe mean clearance of amivantamab-vmjw is 360 ± 144 mL/day.[L34193]
CategoriesImmunoproteins
Patents NumberNA
Date of IssueNA
Date of ExpiryNA
Drug InteractionNA
TargetEpidermal growth factor receptor,Hepatocyte growth factor receptor,Low affinity immunoglobulin gamma Fc region receptor III-A
Brand NameNA
CompanyNA
Brand DescriptionNA
Prescribed ForNA
Chemical NameNA
FormulationNA
Physical Appearance NA
Route of AdministrationNA
Recommended DosageNA
ContraindicationNA
Side EffectsNA
Useful Link 1Link
Useful Link 2NA
RemarksNA


Primary information
ID16152
Therapeutic IDTh1683
Protein NameAmivantamab
Sequence>Th1683_Amivantamab QVQLVQSGAEVAKPGTSVKLSCKASGYTFTDYWMQWVKQRPGQGLEWIGTIYPGDGDTGYAQKFQGKATLTADKSSKTVYMHLSSLASEDSAVYYCARGDYYGSNSLDYWGQGTSVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK
Molecular Weight148000
Chemical FormulaNA
Isoelectric PointNA
HydrophobicityNA
Melting pointNA
Half-lifeThe terminal half life of amivantamab-vmjw is 11.3 ± 4.53 days.[L34193]
DescriptionAmivantamab, 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/DiseaseAmivantamab 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]
PharmacodynamicsAmivantamab 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 ActionMesenchymal-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]
ToxicityData regarding overdoses of amivantamab are not readily available.[L34193] Patients experiencing an overdose should be treated with symptomatic and supportive measures.
MetabolismAntibodies are expected to be metabolized to oligopeptides and amino acids.[A40006]
AbsorptionNA
The mean volume of distribution of amivantamab-vmjw is 5.13 ±1.78 L.[L34193]
ClearanceThe mean clearance of amivantamab-vmjw is 360 ± 144 mL/day.[L34193]
CategoriesProteins
Patents NumberNA
Date of IssueNA
Date of ExpiryNA
Drug InteractionNA
TargetEpidermal growth factor receptor,Hepatocyte growth factor receptor,Low affinity immunoglobulin gamma Fc region receptor III-A
Brand NameNA
CompanyNA
Brand DescriptionNA
Prescribed ForNA
Chemical NameNA
FormulationNA
Physical Appearance NA
Route of AdministrationNA
Recommended DosageNA
ContraindicationNA
Side EffectsNA
Useful Link 1Link
Useful Link 2NA
RemarksNA


Primary information
ID16153
Therapeutic IDTh1683
Protein NameAmivantamab
Sequence>Th1683_Amivantamab QVQLVQSGAEVAKPGTSVKLSCKASGYTFTDYWMQWVKQRPGQGLEWIGTIYPGDGDTGYAQKFQGKATLTADKSSKTVYMHLSSLASEDSAVYYCARGDYYGSNSLDYWGQGTSVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK
Molecular Weight148000
Chemical FormulaNA
Isoelectric PointNA
HydrophobicityNA
Melting pointNA
Half-lifeThe terminal half life of amivantamab-vmjw is 11.3 ± 4.53 days.[L34193]
DescriptionAmivantamab, 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/DiseaseAmivantamab 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]
PharmacodynamicsAmivantamab 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 ActionMesenchymal-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]
ToxicityData regarding overdoses of amivantamab are not readily available.[L34193] Patients experiencing an overdose should be treated with symptomatic and supportive measures.
MetabolismAntibodies are expected to be metabolized to oligopeptides and amino acids.[A40006]
AbsorptionNA
The mean volume of distribution of amivantamab-vmjw is 5.13 ±1.78 L.[L34193]
ClearanceThe mean clearance of amivantamab-vmjw is 360 ± 144 mL/day.[L34193]
CategoriesSerum Globulins
Patents NumberNA
Date of IssueNA
Date of ExpiryNA
Drug InteractionNA
TargetEpidermal growth factor receptor,Hepatocyte growth factor receptor,Low affinity immunoglobulin gamma Fc region receptor III-A
Brand NameNA
CompanyNA
Brand DescriptionNA
Prescribed ForNA
Chemical NameNA
FormulationNA
Physical Appearance NA
Route of AdministrationNA
Recommended DosageNA
ContraindicationNA
Side EffectsNA
Useful Link 1Link
Useful Link 2NA
RemarksNA