Necitumumab

Identification

Name
Necitumumab
Accession Number
DB09559
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).

Type
Biotech
Groups
Approved, Investigational
Biologic Classification
Protein Based Therapies
Monoclonal antibody (mAb)
Protein Structure
Db09559
Protein Chemical Formula
Not Available
Protein Average Weight
Not 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
Synonyms
Not Available
External IDs
  • IMC 11F8
  • IMC-11F8
  • IMC11F8

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.

Associated Conditions
Contraindications & Blackbox Warnings
Learn about our commercial Contraindications & Blackbox Warnings data.
Learn More
Pharmacodynamics
Not 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.

TargetActionsOrganism
AEpidermal growth factor receptor
antagonist
Humans
Absorption
Not Available
Volume of distribution

Steady state volume of distribution is 7.0 L.

Protein binding
Not Available
Metabolism
Not Available
Route of elimination
Not Available
Half-life

Elimination half life is approximately 14 days.

Clearance

14.1 mL/h

Adverse Effects
Learn about our commercial Adverse Effects data.
Learn More
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 organisms
Not Available
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
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.
DrugInteraction
AbciximabThe risk or severity of adverse effects can be increased when Abciximab is combined with Necitumumab.
AdalimumabThe risk or severity of adverse effects can be increased when Adalimumab is combined with Necitumumab.
AlemtuzumabThe risk or severity of adverse effects can be increased when Alemtuzumab is combined with Necitumumab.
AlirocumabThe risk or severity of adverse effects can be increased when Alirocumab is combined with Necitumumab.
Anthrax immune globulin humanThe risk or severity of adverse effects can be increased when Anthrax immune globulin human is combined with Necitumumab.
Antilymphocyte immunoglobulin (horse)The risk or severity of adverse effects can be increased when Antilymphocyte immunoglobulin (horse) is combined with Necitumumab.
Antithymocyte immunoglobulin (rabbit)The risk or severity of adverse effects can be increased when Antithymocyte immunoglobulin (rabbit) is combined with Necitumumab.
Asfotase alfaThe risk or severity of adverse effects can be increased when Asfotase alfa is combined with Necitumumab.
AtezolizumabThe risk or severity of adverse effects can be increased when Necitumumab is combined with Atezolizumab.
AvelumabThe risk or severity of adverse effects can be increased when Necitumumab is combined with Avelumab.
Additional Data Available
  • Extended Description
    Extended Description

    Extended description of the mechanism of action and particular properties of each drug interaction.

    Learn more
  • Severity
    Severity

    A severity rating for each drug interaction, from minor to major.

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  • Evidence Level
    Evidence Level

    A rating for the strength of the evidence supporting each drug interaction.

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  • Action
    Action

    An effect category for each drug interaction. Know how this interaction affects the subject drug.

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Food Interactions
Not Available

Products

Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
PortrazzaSolution16 mgIntravenousEli Lilly & Co. Ltd.Not applicableNot applicableCanada flag
PortrazzaSolution16 mg/1mLIntravenousEli Lilly & Co. Ltd.2015-11-24Not applicableUS flag
Additional Data Available
  • Application Number
    Application Number

    A unique ID assigned by the FDA when a product is submitted for approval by the labeller.

    Learn more
  • Product Code
    Product Code

    A governmentally-recognized ID which uniquely identifies the product within its regulatory market.

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Categories

ATC Codes
L01XC22 — Necitumumab
Drug Categories
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

Chemical Identifiers

UNII
2BT4C47RUI
CAS number
906805-06-9

References

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]
KEGG Drug
D10018
PubChem Substance
347910462
RxNav
1723738
Wikipedia
Necitumumab
AHFS Codes
  • 10:00.00 — Antineoplastic Agents
FDA label
Download (291 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
3Active Not RecruitingTreatmentNon-Small Cell Lung Carcinoma (NSCLC)2
2CompletedTreatmentMalignant Solid Tumours1
2CompletedTreatmentMetastatic Colorectal Cancer (MCRC)1
2CompletedTreatmentNon-Small Cell Lung Carcinoma (NSCLC)2
2CompletedTreatmentSquamous Non Small Cell Lung Cancer1
2CompletedTreatmentTumors, Solid1
2RecruitingTreatmentNon-Small Cell Lung Carcinoma (NSCLC)1
2TerminatedTreatmentMetastatic Non-Small Cell Lung Cancer1
2TerminatedTreatmentSquamous Cell Carcinoma of Lung1
2WithdrawnTreatmentLocally Advanced Squamous Non-Small Cell Lung Cancer / Metastatic Squamous Non-small Cell Lung Cancer1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage Forms
FormRouteStrength
Injection, solution, concentrateIntravenous800 MG
SolutionIntravenous16 mg/1mL
SolutionIntravenous16 mg
Prices
Not Available
Patents
Not Available

Properties

State
Not Available
Experimental Properties
Not Available

Targets

Kind
Protein
Organism
Humans
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, TG...
Gene Name
EGFR
Uniprot ID
P00533
Uniprot Name
Epidermal growth factor receptor
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 September 27, 2020 08:17

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