amivantamab-vmjw

amivantamab-vmjw Uses, Dosage, Side Effects, Food Interaction and all others data.

amivantamab-vmjw, 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. 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. amivantamab-vmjw was found to be more effective than the EGFR inhibitor erlotinib or the MET inhibitor crizotinib in vivo. 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.

amivantamab-vmjw was granted FDA approval on 21 May 2021.

amivantamab-vmjw 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. It has a long duration of action, as activity can be detected up to 8 weeks after treatment. Patients should be counselled regarding the risk of infusion-related reactions, interstitial lung disease and pneumonitis, skin reactions, ocular toxicity, and paronychia. Patients should not take amivantamab if they are pregnant or breastfeeding.

amivantamab-vmjw
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Trade Name	amivantamab-vmjw
Availability	Prescription only
Generic	Amivantamab
Amivantamab Other Names	amivantamab-vmjw
Related Drugs	Opdivo, methotrexate, Keytruda, pembrolizumab, cisplatin, Tagrisso, Avastin
Type
Weight	148000.0 Da (Approximate)
Groups	Approved, Investigational
Therapeutic Class
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Available Country
Last Updated:	September 19, 2023 at 7:00 am

Uses

amivantamab-vmjw 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.

amivantamab-vmjw 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.

amivantamab-vmjw is also used to associated treatment for these conditions: Locally Advanced Non-Small Cell Lung Cancer, Metastatic Non-Small Cell Lung Cancer

How amivantamab-vmjw works

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. 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. 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. Exon 20 insertion mutations in EGFR also lead to conformational changes that activate EGFR.

amivantamab-vmjw 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.

amivantamab-vmjw's binding to the EGFR H epitope shares some of the same amino acids that cetuximab binds to.

amivantamab-vmjw'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. 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. HGF is no longer able to bind to MET, preventing downstream signalling.

amivantamab-vmjw's Fc portion contains 90% less fucose than normal antibodies, allowing for increased binding to the FcγRIIIa region. Binding of the Fc portion of amivantamab-vmjw 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. Binding of amivantamab to the Fc receptor also leads to and increase in levels of IFNγ.

amivantamab-vmjw also significantly downregulates the expression of EGFR and MET on NSCLC cell surfaces, further reducing downstream signalling. EGFR and MET on the cell surface are internalized, and possibly degrading by fusing endosomes with lysosomes. Alternatively, EGFR and MET are the subjects of monocyte-dependent trogocytosis. Trogocytosis allows monocytes to internalize and break down EGFR and MET from the NSCLC cells without cytotoxicity, downmodulating EGFR and MET receptors.

Toxicity

Data regarding overdoses of amivantamab are not readily available. Patients experiencing an overdose should be treated with symptomatic and supportive measures.