Necitumumab

Identification

Summary

Necitumumab is a monoclonal antibody used to treat metastatic squamous non-small cell lung cancer.

Brand Names
Portrazza
Generic Name
Necitumumab
DrugBank Accession Number
DB09559
Background

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
  • Necitumumab
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.

Pharmacology
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Drug Discovery
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Associated Conditions
Contraindications & Blackbox Warnings
Contraindications
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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
Medicalerrors
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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.

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.
AducanumabThe risk or severity of adverse effects can be increased when Necitumumab is combined with Aducanumab.
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.
AmivantamabThe risk or severity of adverse effects can be increased when Necitumumab is combined with Amivantamab.
AnsuvimabThe risk or severity of adverse effects can be increased when Necitumumab is combined with Ansuvimab.
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.
Interactions
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Food Interactions
No interactions found.

Products

Products
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Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
PortrazzaSolution16 mg/1mLIntravenousEli Lilly & Co. Ltd.2015-11-24Not applicableUS flag
PortrazzaInjection, solution, concentrate800 mgIntravenousEli Lilly Nederland B.V.2020-12-21Not applicableEU flag
PortrazzaSolution16 mg / mLIntravenousEli Lilly & Co. Ltd.Not applicableNot applicableCanada flag

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
Affected organisms
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. [Article]
  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. [Article]
  3. Garnock-Jones KP: Necitumumab: First Global Approval. Drugs. 2016 Feb;76(2):283-9. doi: 10.1007/s40265-015-0537-0. [Article]
  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. [Article]
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
2CompletedTreatmentCarcinoma, Non-Small Cell Lung Cancer (NSCLC)1
2CompletedTreatmentMalignant Solid Tumours1
2CompletedTreatmentMetastatic Colorectal Cancer (MCRC)1
2CompletedTreatmentNon-Small Cell Lung Carcinoma (NSCLC)1
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

Pharmacoeconomics

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

Properties

State
Not Available
Experimental Properties
Not Available

Targets

Drugtargets
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Accelerate your drug discovery research with our ADMET & drug target dataset
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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. [Article]

Drug created on November 30, 2015 19:10 / Updated on June 18, 2021 14:15