Amivantamab
Identification
- Summary
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.
- Brand Names
- Rybrevant
- Generic Name
- Amivantamab
- DrugBank Accession Number
- DB16695
- Background
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.1,9 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.1,2 Amivantamab was found to be more effective than the EGFR inhibitor erlotinib or the MET inhibitor crizotinib in vivo.1,3 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.5
Amivantamab was granted FDA approval on 21 May 2021,9 followed by the approval by the EMA on 9 December 2021 12 and Health Canada on 30 March 2022.11
- Type
- Biotech
- Groups
- Approved, Investigational
- Biologic Classification
- Protein Based Therapies
Monoclonal antibody (mAb) - Protein Chemical Formula
- Not Available
- Protein Average Weight
- 148000.0 Da (Approximate)
- Sequences
- Not Available
- Synonyms
- amivantamab-vmjw
- External IDs
- CNTO-4424
- JNJ 61186372
- JNJ-611
- JNJ-61186372
Pharmacology
- Indication
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.9,11,13,14
Reduce drug development failure ratesBuild, train, & validate machine-learning modelswith evidence-based and structured datasets.Build, train, & validate predictive machine-learning models with structured datasets.- Associated Conditions
Indication Type Indication Combined Product Details Approval Level Age Group Patient Characteristics Dose Form Treatment of Locally advanced nsclc •••••••••••• ••••• ••••••• ••••••••••• •• •• ••••• •••••••••••••• ••••••••••••• •••• •••• •• ••••••••• •••••••• ••••••••• Treatment of Metastatic non-small cell lung cancer •••••••••••• ••••• •••• •••• •• ••••••••• ••••••••• ••••••• ••••••••••• •• •• ••••• •••••••••••••• •••••••••••• ••••••••• - Contraindications & Blackbox Warnings
- Prevent Adverse Drug Events TodayTap into our Clinical API for life-saving information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.Avoid life-threatening adverse drug events with our Clinical API
- 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.9 It has a long duration of action, as activity can be detected up to 8 weeks after treatment.1 Patients should be counselled regarding the risk of infusion-related reactions, interstitial lung disease and pneumonitis, skin reactions, ocular toxicity, and paronychia.9 Patients should not take amivantamab if they are pregnant or breastfeeding.9
- 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.1,4 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.1,4 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.5 Exon 20 insertion mutations in EGFR also lead to conformational changes that activate EGFR.6
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.9
Amivantamab's binding to the EGFR H epitope shares some of the same amino acids that cetuximab binds to.1
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.1 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.1 HGF is no longer able to bind to MET, preventing downstream signalling.1
Amivantamab's Fc portion contains 90% less fucose than normal antibodies, allowing for increased binding to the FcγRIIIa region.4 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.4 Binding of amivantamab to the Fc receptor also leads to and increase in levels of IFNγ.6
Amivantamab also significantly downregulates the expression of EGFR and MET on NSCLC cell surfaces, further reducing downstream signalling.6,7 EGFR and MET on the cell surface are internalized, and possibly degrading by fusing endosomes with lysosomes.6 Alternatively, EGFR and MET are the subjects of monocyte-dependent trogocytosis.7 Trogocytosis allows monocytes to internalize and break down EGFR and MET from the NSCLC cells without cytotoxicity, downmodulating EGFR and MET receptors.7
Target Actions Organism AEpidermal growth factor receptor antibodydownregulatorHumans AHepatocyte growth factor receptor antagonistantibodyHumans ALow affinity immunoglobulin gamma Fc region receptor III-A inducerHumans - Absorption
Not Available
- Volume of distribution
The mean volume of distribution of amivantamab-vmjw is 5.13 ±1.78 L.9
- Protein binding
Not Available
- Metabolism
Antibodies are expected to be metabolized to oligopeptides and amino acids.8
- Route of elimination
Not Available
- Half-life
The terminal half life of amivantamab-vmjw is 11.3 ± 4.53 days.9
- Clearance
The mean clearance of amivantamab-vmjw is 360 ± 144 mL/day.9
- Adverse Effects
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- Toxicity
Data regarding overdoses of amivantamab are not readily available.9 Patients experiencing an overdose should be treated with symptomatic and supportive measures.
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs Browse all" title="About SNP Mediated Effects/ADRs" id="snp-actions-info" class="drug-info-popup" href="javascript:void(0);">
- Not Available
Interactions
- Drug Interactions Learn More" title="About Drug Interactions" id="structured-interactions-info" class="drug-info-popup" href="javascript:void(0);">
- This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
Drug Interaction Integrate drug-drug
interactions in your softwareAbciximab The risk or severity of adverse effects can be increased when Abciximab is combined with Amivantamab. Adalimumab The risk or severity of adverse effects can be increased when Adalimumab is combined with Amivantamab. Aducanumab The risk or severity of adverse effects can be increased when Aducanumab is combined with Amivantamab. Alemtuzumab The risk or severity of adverse effects can be increased when Alemtuzumab is combined with Amivantamab. Alirocumab The risk or severity of adverse effects can be increased when Alirocumab is combined with Amivantamab. - Food Interactions
- No interactions found.
Products
- Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.
- International/Other Brands
- Rybrevant (Janssen Pharmaceutical Companies of Johnson & Johnson)
- Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Rybrevant Solution 350 mg / 7 mL Intravenous Janssen Pharmaceuticals 2022-04-26 Not applicable Canada Rybrevant Injection 350 mg/1 Intravenous Janssen Biotech, Inc. 2021-05-21 Not applicable US Rybrevant Injection, solution, concentrate 350 mg Intravenous Janssen Cilag International Nv 2022-05-04 Not applicable EU
Categories
- ATC Codes
- L01FX18 — Amivantamab
- Drug Categories
- Amino Acids, Peptides, and Proteins
- Antibodies
- Antibodies, Monoclonal
- Antineoplastic Agents
- Antineoplastic Agents, Immunological
- Antineoplastic and Immunomodulating Agents
- Bispecific Monoclonal Antibodies
- Blood Proteins
- Globulins
- Immunoglobulins
- Immunoproteins
- MONOCLONAL ANTIBODIES AND ANTIBODY DRUG CONJUGATES
- Proteins
- Serum Globulins
- Chemical TaxonomyProvided by Classyfire
- Description
- Not Available
- Kingdom
- Organic Compounds
- Super Class
- Organic Acids
- Class
- Carboxylic Acids and Derivatives
- Sub Class
- Amino Acids, Peptides, and Analogues
- Direct Parent
- Peptides
- Alternative Parents
- Not Available
- Substituents
- Not Available
- Molecular Framework
- Not Available
- External Descriptors
- Not Available
- Affected organisms
- Not Available
Chemical Identifiers
- UNII
- 0JSR7Z0NB6
- CAS number
- 2171511-58-1
References
- General References
- Neijssen J, Cardoso RMF, Chevalier KM, Wiegman L, Valerius T, Anderson GM, Moores SL, Schuurman J, Parren PWHI, Strohl WR, Chiu ML: Discovery of amivantamab (JNJ-61186372), a bispecific antibody targeting EGFR and MET. J Biol Chem. 2021 Apr 8:100641. doi: 10.1016/j.jbc.2021.100641. [Article]
- Jarantow SW, Bushey BS, Pardinas JR, Boakye K, Lacy ER, Sanders R, Sepulveda MA, Moores SL, Chiu ML: Impact of Cell-surface Antigen Expression on Target Engagement and Function of an Epidermal Growth Factor Receptor x c-MET Bispecific Antibody. J Biol Chem. 2015 Oct 9;290(41):24689-704. doi: 10.1074/jbc.M115.651653. Epub 2015 Aug 10. [Article]
- Moores SL, Chiu ML, Bushey BS, Chevalier K, Luistro L, Dorn K, Brezski RJ, Haytko P, Kelly T, Wu SJ, Martin PL, Neijssen J, Parren PW, Schuurman J, Attar RM, Laquerre S, Lorenzi MV, Anderson GM: A Novel Bispecific Antibody Targeting EGFR and cMet Is Effective against EGFR Inhibitor-Resistant Lung Tumors. Cancer Res. 2016 Jul 1;76(13):3942-53. doi: 10.1158/0008-5472.CAN-15-2833. Epub 2016 May 23. [Article]
- Grugan KD, Dorn K, Jarantow SW, Bushey BS, Pardinas JR, Laquerre S, Moores SL, Chiu ML: Fc-mediated activity of EGFR x c-Met bispecific antibody JNJ-61186372 enhanced killing of lung cancer cells. MAbs. 2017 Jan;9(1):114-126. doi: 10.1080/19420862.2016.1249079. Epub 2016 Oct 27. [Article]
- Metro G, Baglivo S, Bellezza G, Mandarano M, Gili A, Marchetti G, Toraldo M, Molica C, Reda MS, Tofanetti FR, Siggillino A, Prosperi E, Giglietti A, Di Girolamo B, Garaffa M, Marasciulo F, Minotti V, Gunnellini M, Guida A, Sassi M, Sidoni A, Roila F, Ludovini V: Sensitivity to Immune Checkpoint Blockade in Advanced Non-Small Cell Lung Cancer Patients with EGFR Exon 20 Insertion Mutations. Genes (Basel). 2021 Apr 30;12(5). pii: genes12050679. doi: 10.3390/genes12050679. [Article]
- Yun J, Lee SH, Kim SY, Jeong SY, Kim JH, Pyo KH, Park CW, Heo SG, Yun MR, Lim S, Lim SM, Hong MH, Kim HR, Thayu M, Curtin JC, Knoblauch RE, Lorenzi MV, Roshak A, Cho BC: Antitumor Activity of Amivantamab (JNJ-61186372), an EGFR-MET Bispecific Antibody, in Diverse Models of EGFR Exon 20 Insertion-Driven NSCLC. Cancer Discov. 2020 Aug;10(8):1194-1209. doi: 10.1158/2159-8290.CD-20-0116. Epub 2020 May 15. [Article]
- Vijayaraghavan S, Lipfert L, Chevalier K, Bushey BS, Henley B, Lenhart R, Sendecki J, Beqiri M, Millar HJ, Packman K, Lorenzi MV, Laquerre S, Moores SL: Amivantamab (JNJ-61186372), an Fc Enhanced EGFR/cMet Bispecific Antibody, Induces Receptor Downmodulation and Antitumor Activity by Monocyte/Macrophage Trogocytosis. Mol Cancer Ther. 2020 Oct;19(10):2044-2056. doi: 10.1158/1535-7163.MCT-20-0071. Epub 2020 Aug 3. [Article]
- Ryman JT, Meibohm B: Pharmacokinetics of Monoclonal Antibodies. CPT Pharmacometrics Syst Pharmacol. 2017 Sep;6(9):576-588. doi: 10.1002/psp4.12224. Epub 2017 Jul 29. [Article]
- FDA Approved Drug Products: Rybrevant (Amivantamab-vmjw) Intravenous Injection [Link]
- US Patent: US9593164B2 [Link]
- Health Canada Approved Drug Products: Rybrevant (amivantamab) injection, for intravenous infusion [Link]
- European Medicines Agency Medicines: Rybrevant (amivantamab) [Link]
- EMA Approved Drug Products: Rybrevant (amivantamab) intravenous injection [Link]
- FDA Approved Drug Products: RYBREVANT (amivantamab-vmjw) injection, for intravenous use (November 2022) [Link]
- External Links
- 2549198
- Wikipedia
- Amivantamab
Clinical Trials
- Clinical Trials Learn More" title="About Clinical Trials" id="clinical-trials-info" class="drug-info-popup" href="javascript:void(0);">
Phase Status Purpose Conditions Count 3 Active Not Recruiting Treatment Metastatic or Advanced Non-Small Cell Lung Cancer (NSCLC) 1 3 Active Not Recruiting Treatment Non-Small Cell Lung Carcinoma 3 2 Active Not Recruiting Treatment Metastatic Non-Small Cell Lung Cancer / Recurrent Non-small Cell Lung Cancer 1 2 Completed Treatment Esophageal Neoplasms / Neoplasm of Stomach 1 2 Not Yet Recruiting Treatment Non-Small Cell Lung Carcinoma 2
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Injection Intravenous 350 mg/1 Injection, solution, concentrate Intravenous 350 mg Solution Intravenous 350 mg / 7 mL Solution Intravenous 350.00 mg - Prices
- Not Available
- Patents
- Not Available
Properties
- State
- Liquid
- Experimental Properties
- Not Available
Targets
![](https://go.drugbank.com/assets/locked/DrugTargets2-682eb846d210ae4bf33ca03febccfb57bb1c61318e699b729e5df4dfab2c5b67.png)
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- AntibodyDownregulator
- General Function
- Ubiquitin protein ligase binding
- Specific Function
- Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades to convert extracellular cues into appropriate cellular responses. Known ligands include EGF, TG...
- Gene Name
- EGFR
- Uniprot ID
- P00533
- Uniprot Name
- Epidermal growth factor receptor
- Molecular Weight
- 134276.185 Da
References
- Neijssen J, Cardoso RMF, Chevalier KM, Wiegman L, Valerius T, Anderson GM, Moores SL, Schuurman J, Parren PWHI, Strohl WR, Chiu ML: Discovery of amivantamab (JNJ-61186372), a bispecific antibody targeting EGFR and MET. J Biol Chem. 2021 Apr 8:100641. doi: 10.1016/j.jbc.2021.100641. [Article]
- Vijayaraghavan S, Lipfert L, Chevalier K, Bushey BS, Henley B, Lenhart R, Sendecki J, Beqiri M, Millar HJ, Packman K, Lorenzi MV, Laquerre S, Moores SL: Amivantamab (JNJ-61186372), an Fc Enhanced EGFR/cMet Bispecific Antibody, Induces Receptor Downmodulation and Antitumor Activity by Monocyte/Macrophage Trogocytosis. Mol Cancer Ther. 2020 Oct;19(10):2044-2056. doi: 10.1158/1535-7163.MCT-20-0071. Epub 2020 Aug 3. [Article]
- Cavaliere A, Sun S, Lee S, Bodner J, Li Z, Huang Y, Moores SL, Marquez-Nostra B: Development of [(89)Zr]ZrDFO-amivantamab bispecific to EGFR and c-MET for PET imaging of triple-negative breast cancer. Eur J Nucl Med Mol Imaging. 2021 Feb;48(2):383-394. doi: 10.1007/s00259-020-04978-6. Epub 2020 Aug 8. [Article]
- FDA Approved Drug Products: Rybrevant (Amivantamab-vmjw) Intravenous Injection [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- AntagonistAntibody
- General Function
- Protein tyrosine kinase activity
- Specific Function
- Receptor tyrosine kinase that transduces signals from the extracellular matrix into the cytoplasm by binding to hepatocyte growth factor/HGF ligand. Regulates many physiological processes including...
- Gene Name
- MET
- Uniprot ID
- P08581
- Uniprot Name
- Hepatocyte growth factor receptor
- Molecular Weight
- 155540.035 Da
References
- Neijssen J, Cardoso RMF, Chevalier KM, Wiegman L, Valerius T, Anderson GM, Moores SL, Schuurman J, Parren PWHI, Strohl WR, Chiu ML: Discovery of amivantamab (JNJ-61186372), a bispecific antibody targeting EGFR and MET. J Biol Chem. 2021 Apr 8:100641. doi: 10.1016/j.jbc.2021.100641. [Article]
- Cavaliere A, Sun S, Lee S, Bodner J, Li Z, Huang Y, Moores SL, Marquez-Nostra B: Development of [(89)Zr]ZrDFO-amivantamab bispecific to EGFR and c-MET for PET imaging of triple-negative breast cancer. Eur J Nucl Med Mol Imaging. 2021 Feb;48(2):383-394. doi: 10.1007/s00259-020-04978-6. Epub 2020 Aug 8. [Article]
- FDA Approved Drug Products: Rybrevant (Amivantamab-vmjw) Intravenous Injection [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Inducer
- General Function
- Not Available
- Specific Function
- Receptor for the Fc region of IgG. Binds complexed or aggregated IgG and also monomeric IgG. Mediates antibody-dependent cellular cytotoxicity (ADCC) and other antibody-dependent responses, such as...
- Gene Name
- FCGR3A
- Uniprot ID
- P08637
- Uniprot Name
- Low affinity immunoglobulin gamma Fc region receptor III-A
- Molecular Weight
- 29088.895 Da
References
- Grugan KD, Dorn K, Jarantow SW, Bushey BS, Pardinas JR, Laquerre S, Moores SL, Chiu ML: Fc-mediated activity of EGFR x c-Met bispecific antibody JNJ-61186372 enhanced killing of lung cancer cells. MAbs. 2017 Jan;9(1):114-126. doi: 10.1080/19420862.2016.1249079. Epub 2016 Oct 27. [Article]
Drug created at May 22, 2021 03:10 / Updated at December 01, 2022 11:30