Identification

Name
Necitumumab
Accession Number
DB09559  (DB05774)
Type
Biotech
Groups
Approved
Biologic Classification
Protein Based Therapies
Monoclonal antibody (mAb)
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 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
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
PortrazzaSolution16 mgIntravenousEli Lilly & Co. Ltd.Not applicableNot applicableCanada
PortrazzaSolution16 mg/mLIntravenousEli Lilly & Co. Ltd.2015-11-24Not applicableUs
Categories
UNII
2BT4C47RUI
CAS number
906805-06-9

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
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
Human
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

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
DrugInteractionDrug group
AcetyldigitoxinAcetyldigitoxin may decrease the cardiotoxic activities of Necitumumab.Approved
AcetyldigoxinAcetyldigoxin may decrease the cardiotoxic activities of Necitumumab.Experimental
BCG vaccineThe therapeutic efficacy of BCG vaccine can be decreased when used in combination with Necitumumab.Investigational
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
Clostridium tetani toxoid antigen (formaldehyde inactivated)The therapeutic efficacy of Clostridium tetani toxoid antigen (formaldehyde inactivated) can be decreased when used in combination with Necitumumab.Approved
Corynebacterium diphtheriae toxoid antigen (formaldehyde inactivated)The therapeutic efficacy of Corynebacterium diphtheriae toxoid antigen (formaldehyde inactivated) can be decreased when used in combination with Necitumumab.Approved
CyclophosphamideCyclophosphamide may increase the cardiotoxic activities of Necitumumab.Approved, Investigational
CymarinCymarin may decrease the cardiotoxic activities of Necitumumab.Experimental
DeslanosideDeslanoside may decrease the cardiotoxic activities of Necitumumab.Approved
DigitoxinDigitoxin may decrease the cardiotoxic activities of Necitumumab.Approved, Investigational
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
GI-5005The therapeutic efficacy of GI-5005 can be decreased when used in combination with Necitumumab.Investigational
GitoformateGitoformate may decrease the cardiotoxic activities of Necitumumab.Experimental
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
Lanatoside CLanatoside C may decrease the cardiotoxic activities of Necitumumab.Experimental
MetildigoxinMetildigoxin may decrease the cardiotoxic activities of Necitumumab.Experimental
OleandrinOleandrin may decrease the cardiotoxic activities of Necitumumab.Experimental, Investigational
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
PeruvosidePeruvoside may decrease the cardiotoxic activities of Necitumumab.Experimental
ProscillaridinProscillaridin may decrease the cardiotoxic activities of Necitumumab.Experimental
Rabies virus inactivated antigen, AThe therapeutic efficacy of Rabies virus inactivated antigen, A can be decreased when used in combination with Necitumumab.Approved
RindopepimutThe therapeutic efficacy of Rindopepimut can be decreased when used in combination with Necitumumab.Investigational
Rotavirus VaccineThe therapeutic efficacy of Rotavirus Vaccine can be decreased when used in combination with Necitumumab.Approved
Rubella virus vaccineThe therapeutic efficacy of Rubella virus vaccine can be decreased when used in combination with Necitumumab.Approved
SRP 299The therapeutic efficacy of SRP 299 can be decreased when used in combination with Necitumumab.Investigational
TecemotideThe therapeutic efficacy of Tecemotide can be decreased when used in combination with Necitumumab.Investigational
TG4010The therapeutic efficacy of TG4010 can be decreased when used in combination with Necitumumab.Investigational
TrastuzumabTrastuzumab may increase the cardiotoxic activities of Necitumumab.Approved, Investigational
Yellow fever vaccineThe therapeutic efficacy of Yellow fever vaccine can be decreased when used in combination with Necitumumab.Approved
Zoster vaccineThe therapeutic efficacy of Zoster vaccine can be decreased when used in combination with Necitumumab.Approved
Food Interactions
Not Available

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]
External Links
KEGG Drug
D10018
PubChem Substance
347910462
Wikipedia
Necitumumab
ATC Codes
L01XC22 — Necitumumab
AHFS Codes
  • 10:00.00 — Antineoplastic Agents
FDA label
Download (291 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1Active Not RecruitingTreatmentLung Cancer Non-Small Cell Cancer (NSCLC) / Neoplasms Metastasis1
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
1RecruitingTreatmentLung Cancer Non-Small Cell Cancer (NSCLC)1
1, 2Active Not RecruitingTreatmentSquamous Non-Small Cell Lung Cancer1
2Active Not RecruitingTreatmentMetastatic Non-Small Cell Lung Cancer1
2CompletedTreatmentLung Cancer Non-Small Cell Cancer (NSCLC)1
2CompletedTreatmentMalignant Solid Tumours1
2CompletedTreatmentMetastatic Colorectal Cancers1
2CompletedTreatmentSquamous Non Small Cell Lung Cancer1
2CompletedTreatmentTumors, Solid1
2RecruitingTreatmentLung Cancer Non-Small Cell Cancer (NSCLC)1
2WithdrawnTreatmentLocally Advanced Squamous Non-Small Cell Lung Cancer / Metastatic Squamous Non-small Cell Lung Cancer1
3Active Not RecruitingTreatmentLung Cancer Non-Small Cell Cancer (NSCLC)2

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
FormRouteStrength
SolutionIntravenous16 mg
SolutionIntravenous16 mg/mL
Prices
Not Available
Patents
Not Available

Properties

State
Not Available
Experimental Properties
Not Available

Taxonomy

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

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, 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 November 13, 2017 21:49