Identification
NameNecitumumab
Accession NumberDB09559  (DB05774)
TypeBiotech
GroupsApproved
Description

Necitumumab is an intravenously administered recombinant monoclonal IgG1 antibody used in the treatment of non-small cell lung cancer (NSCLC) as an EGFR antagonist. It functions by binding to epidermal growth factor receptor (EGFR) and prevents binding of its ligands, a process that is involved in cell proliferation, metastasis, angiogenesis, and malignant progression. Binding of necitumumab to EGFR induces receptor internalization and degradation, thereby preventing further activation of EGFR which is beneficial in NSCLC as many patients have increased protein expression of EGFR. Necitumumab is approved for use in combination with cisplatin and gemcitabine as a first-line treatment for metastatic squamous non-small cell lung cancer (NSCLC).

Protein structureDb09559
Related Articles
Protein chemical formulaNot Available
Protein average weightNot Available
Sequences
>Sequence A
QVQLQESGPGLVKPSQTLSLTCTVSGGSISSGDYYWSWIRQPPGKGLEWIGYIYYSGSTD
YNPSLKSRVTMSVDTSKNQFSLKVNSVTAADTAVYYCARVSIFGVGTFDYWGQGTLVTVS
SASTKGPSVLPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQS
SGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPELLG
GPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQY
NSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRE
EMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSR
WQQGNVFSCSVMHEALHNHYTQKSLSLSPGK
>Sequence A'
QVQLQESGPGLVKPSQTLSLTCTVSGGSISSGDYYWSWIRQPPGKGLEWIGYIYYSGSTD
YNPSLKSRVTMSVDTSKNQFSLKVNSVTAADTAVYYCARVSIFGVGTFDYWGQGTLVTVS
SASTKGPSVLPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQS
SGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPELLG
GPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQY
NSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRE
EMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSR
WQQGNVFSCSVMHEALHNHYTQKSLSLSPGK
>Sequence B
EIVMTQSPATLSLSPGERATLSCRASQSVSSYLAWYQQKPGQAPRLLIYDASNRATGIPA
RFSGSGSGTDFTLTISSLEPEDFAVYYCHQYGSTPLTFGGGTKAEIKRTVAAPSVFIFPP
SDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLT
LSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC
>Sequence B'
EIVMTQSPATLSLSPGERATLSCRASQSVSSYLAWYQQKPGQAPRLLIYDASNRATGIPA
RFSGSGSGTDFTLTISSLEPEDFAVYYCHQYGSTPLTFGGGTKAEIKRTVAAPSVFIFPP
SDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLT
LSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC
Download FASTA Format
SynonymsNot Available
External IDs IMC 11F8 / IMC-11F8 / IMC11F8
Product Ingredients Not Available
Approved Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
PortrazzaSolution16 mgIntravenousEli Lilly & Co. Ltd.Not applicableNot applicableCanada
PortrazzaSolution16 mg/mLIntravenousEli Lilly & Co. Ltd.2015-11-24Not applicableUs
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International BrandsNot Available
Brand mixturesNot Available
Categories
UNII2BT4C47RUI
CAS number906805-06-9
Pharmacology
Indication

Necitumumab is approved for use in combination with cisplatin and gemcitabine as a first-line treatment for metastatic squamous non-small cell lung cancer (NSCLC). It is not indicated for treatment of non-squamous NSCLC.

Structured Indications
PharmacodynamicsNot Available
Mechanism of action

Necitumumab is an EGFR antagonist that functions by binding to epidermal growth factor receptor (EGFR) and preventing binding of its ligands, a process that is involved in cell proliferation, metastasis, angiogenesis, and malignant progression. Binding of necitumumab to EGFR induces receptor internalization and degradation.

TargetKindPharmacological actionActionsOrganismUniProt ID
Epidermal growth factor receptorProteinyes
antagonist
HumanP00533 details
Related Articles
AbsorptionNot Available
Volume of distribution

Steady state volume of distribution is 7.0 L.

Protein bindingNot Available
MetabolismNot Available
Route of eliminationNot Available
Half life

Elimination half life is approximately 14 days.

Clearance

14.1 mL/h

Toxicity

The poor safety profile of necitumumab has been one of the major limitations of its use. Rigorous monitoring of the following adverse events is recommended for the use of this drug: cardiopulmonary arrest, hypomagnesia, venous and arterial thromboembolic events, dermatologic toxicities, and infusion-related reactions. Due to observations of increased toxicity and mortality in treatment of non-squamous NSCLC, necitumumab is only recommended for the treatment of squamous NSCLC in combination with cisplatin and gemcitabine. Animal studies suggest potential embryo-fetal toxicity.

Affected organismsNot Available
PathwaysNot Available
Pharmacogenomic Effects/ADRs Not Available
Interactions
Drug Interactions
DrugInteractionDrug group
AcetyldigitoxinAcetyldigitoxin may decrease the cardiotoxic activities of Necitumumab.Approved
BelimumabThe risk or severity of adverse effects can be increased when Necitumumab is combined with Belimumab.Approved
BevacizumabBevacizumab may increase the cardiotoxic activities of Necitumumab.Approved, Investigational
CabazitaxelThe risk or severity of adverse effects can be increased when Cabazitaxel is combined with Necitumumab.Approved
CyclophosphamideCyclophosphamide may increase the cardiotoxic activities of Necitumumab.Approved, Investigational
DeslanosideDeslanoside may decrease the cardiotoxic activities of Necitumumab.Approved
DigitoxinDigitoxin may decrease the cardiotoxic activities of Necitumumab.Approved
DigoxinDigoxin may decrease the cardiotoxic activities of Necitumumab.Approved
DocetaxelThe risk or severity of adverse effects can be increased when Docetaxel is combined with Necitumumab.Approved, Investigational
G17DTThe therapeutic efficacy of G17DT can be decreased when used in combination with Necitumumab.Investigational
INGN 201The therapeutic efficacy of INGN 201 can be decreased when used in combination with Necitumumab.Investigational
INGN 225The therapeutic efficacy of INGN 225 can be decreased when used in combination with Necitumumab.Investigational
OleandrinAnvirzel may decrease the cardiotoxic activities of Necitumumab.Experimental
OuabainOuabain may decrease the cardiotoxic activities of Necitumumab.Approved
PaclitaxelThe risk or severity of adverse effects can be increased when Paclitaxel is combined with Necitumumab.Approved, Vet Approved
RindopepimutThe therapeutic efficacy of CDX-110 can be decreased when used in combination with Necitumumab.Investigational
SRP 299The therapeutic efficacy of SRP 299 can be decreased when used in combination with Necitumumab.Investigational
TrastuzumabTrastuzumab may increase the cardiotoxic activities of Necitumumab.Approved, Investigational
Food InteractionsNot Available
References
Synthesis ReferenceNot Available
General References
  1. Lu D, Zhang H, Koo H, Tonra J, Balderes P, Prewett M, Corcoran E, Mangalampalli V, Bassi R, Anselma D, Patel D, Kang X, Ludwig DL, Hicklin DJ, Bohlen P, Witte L, Zhu Z: A fully human recombinant IgG-like bispecific antibody to both the epidermal growth factor receptor and the insulin-like growth factor receptor for enhanced antitumor activity. J Biol Chem. 2005 May 20;280(20):19665-72. Epub 2005 Mar 9. [PubMed:15757893 ]
  2. Kuenen B, Witteveen PO, Ruijter R, Giaccone G, Dontabhaktuni A, Fox F, Katz T, Youssoufian H, Zhu J, Rowinsky EK, Voest EE: A phase I pharmacologic study of necitumumab (IMC-11F8), a fully human IgG1 monoclonal antibody directed against EGFR in patients with advanced solid malignancies. Clin Cancer Res. 2010 Mar 15;16(6):1915-23. doi: 10.1158/1078-0432.CCR-09-2425. Epub 2010 Mar 2. [PubMed:20197484 ]
  3. Garnock-Jones KP: Necitumumab: First Global Approval. Drugs. 2016 Feb;76(2):283-9. doi: 10.1007/s40265-015-0537-0. [PubMed:26729188 ]
  4. Zhou F, Zhou C: Necitumumab for patients with non-squamous NSCLC: uninspiring results. Lancet Oncol. 2015 Mar;16(3):246-7. doi: 10.1016/S1470-2045(15)70059-8. Epub 2015 Feb 18. [PubMed:25701169 ]
External Links
ATC CodesL01XC22 — Necitumumab
AHFS Codes
  • 10:00
PDB EntriesNot Available
FDA labelDownload (291 KB)
MSDSNot Available
Clinical Trials
Clinical Trials
PhaseStatusPurposeConditionsCount
1Active Not RecruitingTreatmentNeoplasms Metastasis / Non-Small-Cell Lung Carcinoma (NSCLC)1
1Active Not RecruitingTreatmentStage IV Non-Small Cell Lung Cancer1
1CompletedNot AvailableTumors, Solid1
1CompletedTreatmentAdvanced Solid Tumors / Neoplasms1
1Not Yet RecruitingTreatmentNon-Small Cell Lung Carcinoma (NSCLC)1
1RecruitingTreatmentEGFR Activating Mutation / EGFR Exon 19 Deletion Mutation / EGFR NP_005219.2:p.G719X / EGFR NP_005219.2:p.L858R / EGFR NP_005219.2:p.L861Q / EGFR T790M Mutation Negative / Recurrent Non-Small Cell Lung Carcinoma / Stage IV Non-Small Cell Lung Cancer / Stage IV Non-Small Cell Lung Cancer AJCC v71
1RecruitingTreatmentNon-Small-Cell Lung Carcinoma (NSCLC)1
1, 2Active Not RecruitingTreatmentSquamous Non-Small Cell Lung Cancer1
2Active Not RecruitingTreatmentMetastatic Non-Small Cell Lung Cancer1
2Active Not RecruitingTreatmentSquamous Non Small Cell Lung Cancer1
2CompletedTreatmentMalignant Solid Tumours1
2CompletedTreatmentMetastatic Colorectal Cancers1
2CompletedTreatmentNon-Small-Cell Lung Carcinoma (NSCLC)1
2CompletedTreatmentTumors, Solid1
2RecruitingTreatmentNon-Small-Cell Lung Carcinoma (NSCLC)1
2WithdrawnTreatmentLocally Advanced Squamous Non-Small Cell Lung Cancer / Metastatic Squamous Non-small Cell Lung Cancer1
3Active Not RecruitingTreatmentNon-Small-Cell Lung Carcinoma (NSCLC)2
Pharmacoeconomics
ManufacturersNot Available
PackagersNot Available
Dosage forms
FormRouteStrength
SolutionIntravenous16 mg
SolutionIntravenous16 mg/mL
PricesNot Available
PatentsNot Available
Properties
StateNot Available
Experimental PropertiesNot Available
Taxonomy
DescriptionNot Available
KingdomOrganic Compounds
Super ClassOrganic Acids
ClassCarboxylic Acids and Derivatives
Sub ClassAmino Acids, Peptides, and Analogues
Direct ParentPeptides
Alternative ParentsNot Available
SubstituentsNot Available
Molecular FrameworkNot Available
External DescriptorsNot Available

Targets

Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
antagonist
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, TGFA/TGF-alpha, amphiregulin, epigen/EPGN, BTC/betacellulin, epiregulin/EREG and HBEGF/heparin-binding EGF. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation on ke...
Gene Name:
EGFR
Uniprot ID:
P00533
Molecular Weight:
134276.185 Da
References
  1. Kuenen B, Witteveen PO, Ruijter R, Giaccone G, Dontabhaktuni A, Fox F, Katz T, Youssoufian H, Zhu J, Rowinsky EK, Voest EE: A phase I pharmacologic study of necitumumab (IMC-11F8), a fully human IgG1 monoclonal antibody directed against EGFR in patients with advanced solid malignancies. Clin Cancer Res. 2010 Mar 15;16(6):1915-23. doi: 10.1158/1078-0432.CCR-09-2425. Epub 2010 Mar 2. [PubMed:20197484 ]
Drug created on November 30, 2015 12:10 / Updated on June 07, 2017 16:53