Cetuximab

Identification

Name
Cetuximab
Accession Number
DB00002
Description

Cetuximab is an epidermal growth factor receptor binding FAB. Cetuximab is composed of the Fv (variable; antigen-binding) regions of the 225 murine EGFr monoclonal antibody specific for the N-terminal portion of human EGFr with human IgG1 heavy and kappa light chain constant (framework) regions. Cetuximab is marketed under the brand Erbitux® by Eli Lilly and Company. In the United States, a regimen of cetuximab costs approximately $30,790 for an eight-week course.

Type
Biotech
Groups
Approved
Biologic Classification
Protein Based Therapies
Monoclonal antibody (mAb)
Protein Structure
Db00002
Protein Chemical Formula
C6484H10042N1732O2023S36
Protein Average Weight
145781.6 Da
Sequences
>Cetuximab heavy chain
QVQLKQSGPGLVQPSQSLSITCTVSGFSLTNYGVHWVRQSPGKGLEWLGVIWSGGNTDYN
TPFTSRLSINKDNSKSQVFFKMNSLQSNDTAIYYCARALTYYDYEFAYWGQGTLVTVSAA
STKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSG
LYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGP
SVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNS
TYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDEL
TKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQ
QGNVFSCSVMHEALHNHYTQKSLSLSPGK
>Cetuximab light chain
DILLTQSPVILSVSPGERVSFSCRASQSIGTNIHWYQQRTNGSPRLLIKYASESISGIPS
RFSGSGSGTDFTLSINSVESEDIADYYCQQNNNWPTTFGAGTKLELKRTVAAPSVFIFPP
SDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLT
LSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC
Download FASTA Format
Synonyms
  • Cetuximab
  • Cétuximab
  • Cetuximabum
External IDs
  • ABP-494
  • BMS 564717
  • C-225
  • C225
  • CMAB-009
  • CMAB009
  • IMC-225
  • IMC-C225
  • MOAB C225

Pharmacology

Indication

Cetuximab, used in combination with irinotecan, is indicated for the treatment of EGFR-expressing, metastatic colorectal carcinoma in patients who are refractory to irinotecan-based chemotherapy. Cetuximab administered as a single agent is indicated for the treatment of EGFR-expressing, metastatic colorectal carcinoma in patients who are intolerant to irinotecan-based chemotherapy.

Associated Conditions
Contraindications & Blackbox Warnings
Learn about our commercial Contraindications & Blackbox Warnings data.
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Pharmacodynamics

Used in the treatment of colorectal cancer, cetuximab binds specifically to the epidermal growth factor receptor (EGFr, HER1, c-ErbB-1) on both normal and tumor cells. EGFr is over-expressed in many colorectal cancers. Cetuximab competitively inhibits the binding of epidermal growth factor (EGF) and other ligands, such as transforming growth factor–alpha. Binding of cetuximab to the EGFr blocks phosphorylation and activation of receptor-associated kinases, resulting in inhibition of cell growth, induction of apoptosis, decreased matrix metalloproteinase secretion and reduced vascular endothelial growth factor production.

Mechanism of action

Cetuximab binds to the epidermal growth factor receptor (EGFr) on both normal and tumor cells. EGFr is over-expressed in many colorectal cancers. Cetuximab competitively inhibits the binding of epidermal growth factor (EGF) and TGF alpha, thereby reducing their effects on cell growth and metastatic spread.

TargetActionsOrganism
AEpidermal growth factor receptor
antagonist
Humans
ULow affinity immunoglobulin gamma Fc region receptor III-BNot AvailableHumans
UComplement C1q subcomponent subunit ANot AvailableHumans
UComplement C1q subcomponent subunit BNot AvailableHumans
UComplement C1q subcomponent subunit CNot AvailableHumans
ULow affinity immunoglobulin gamma Fc region receptor III-ANot AvailableHumans
UHigh affinity immunoglobulin gamma Fc receptor INot AvailableHumans
ULow affinity immunoglobulin gamma Fc region receptor II-aNot AvailableHumans
Absorption
Not Available
Volume of distribution

appeared to be independent of dose and approximated the vascular space of 2-3 L/m2.

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

The mean half-life for Cetuximab is 114 hours (range 75-188 hours).

Clearance

Female patients had 25% lower intrinsic clearance than male patients.

Adverse Effects
Learn about our commercial Adverse Effects data.
Learn More
Toxicity

Pulmonary Toxicity

Interstitial lung disease (ILD) was reported in 3 of 633 (<0.5%) patients with advanced colorectal cancer receiving cetuximab. Interstitial pneumonitis with non-cardiogenic pulmonary edema resulting in death was reported in one case. Two patients had pre-existing fibrotic lung disease and experienced an acute exacerbation of their disease while receiving cetuximab in combination with irinotecan. In the clinical investigational program, an additional case of interstitial pneumonitis was reported in a patient with head and neck cancer treated with cetuximab and cisplatin. The onset of symptoms occurred between the fourth and eleventh doses of treatment in all reported cases.

Affected organisms
  • Humans and other mammals
Pathways
PathwayCategory
Cetuximab Action PathwayDrug action
Pharmacogenomic Effects/ADRs
Interacting Gene/EnzymeAllele nameGenotype(s)Defining Change(s)Type(s)DescriptionDetails
Low affinity immunoglobulin gamma Fc region receptor II-a---(T;T) / (C;T)H allelleEffect Directly StudiedPatients with this genotype may have increased progression-free survival time when using cetuximab to treat colorectal cancer.Details
Low affinity immunoglobulin gamma Fc region receptor III-A---(T;T) / (G;T)G > TEffect Directly StudiedPatients with this genotype have increased progression-free survival time when using cetuximab to treat colorectal cancer.Details

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 Cetuximab is combined with Abciximab.
AdalimumabThe risk or severity of adverse effects can be increased when Cetuximab is combined with Adalimumab.
AlemtuzumabThe risk or severity of adverse effects can be increased when Cetuximab is combined with Alemtuzumab.
AlirocumabThe risk or severity of adverse effects can be increased when Cetuximab is combined with Alirocumab.
Anthrax immune globulin humanThe risk or severity of adverse effects can be increased when Cetuximab is combined with Anthrax immune globulin human.
Antilymphocyte immunoglobulin (horse)The risk or severity of adverse effects can be increased when Cetuximab is combined with Antilymphocyte immunoglobulin (horse).
Antithymocyte immunoglobulin (rabbit)The risk or severity of adverse effects can be increased when Cetuximab is combined with Antithymocyte immunoglobulin (rabbit).
Asfotase alfaThe risk or severity of adverse effects can be increased when Cetuximab is combined with Asfotase alfa.
AtezolizumabThe risk or severity of adverse effects can be increased when Cetuximab is combined with Atezolizumab.
AvelumabThe risk or severity of adverse effects can be increased when Cetuximab 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.

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  • 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
ErbituxSolution2 mg/1mLIntravenousImClone LLC2004-02-12Not applicableUS flag
ErbituxInjection, solution5 mg/mlIntravenousMerck K Ga A2004-06-29Not applicableEU flag
ErbituxSolution2 mgIntravenousImClone LLC2008-10-28Not applicableCanada flag
ErbituxSolution2 mg/1mLIntravenousImClone LLC2007-10-02Not applicableUS flag
ErbituxInjection, solution5 mg/mlIntravenousMerck K Ga A2004-06-29Not applicableEU 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.

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  • Product Code
    Product Code

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

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Categories

ATC Codes
L01XC06 — Cetuximab
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
PQX0D8J21J
CAS number
205923-56-4

References

General References
  1. Hosokawa N, Yamamoto S, Uehara Y, Hori M, Tsuchiya KS: Effect of thiazinotrienomycin B, an ansamycin antibiotic, on the function of epidermal growth factor receptor in human stomach tumor cells. J Antibiot (Tokyo). 1999 May;52(5):485-90. [PubMed:10480573]
  2. Wakita H, Takigawa M: Activation of epidermal growth factor receptor promotes late terminal differentiation of cell-matrix interaction-disrupted keratinocytes. J Biol Chem. 1999 Dec 24;274(52):37285-91. [PubMed:10601294]
  3. Suwa T, Ueda M, Jinno H, Ozawa S, Kitagawa Y, Ando N, Kitajima M: Epidermal growth factor receptor-dependent cytotoxic effect of anti-EGFR antibody-ribonuclease conjugate on human cancer cells. Anticancer Res. 1999 Sep-Oct;19(5B):4161-5. [PubMed:10628369]
  4. Burke P, Schooler K, Wiley HS: Regulation of epidermal growth factor receptor signaling by endocytosis and intracellular trafficking. Mol Biol Cell. 2001 Jun;12(6):1897-910. [PubMed:11408594]
  5. Viloria-Petit A, Crombet T, Jothy S, Hicklin D, Bohlen P, Schlaeppi JM, Rak J, Kerbel RS: Acquired resistance to the antitumor effect of epidermal growth factor receptor-blocking antibodies in vivo: a role for altered tumor angiogenesis. Cancer Res. 2001 Jul 1;61(13):5090-101. [PubMed:11431346]
  6. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]
  7. Schrag D: The price tag on progress--chemotherapy for colorectal cancer. N Engl J Med. 2004 Jul 22;351(4):317-9. [PubMed:15269308]
  8. Snyder LC, Astsaturov I, Weiner LM: Overview of monoclonal antibodies and small molecules targeting the epidermal growth factor receptor pathway in colorectal cancer. Clin Colorectal Cancer. 2005 Nov;5 Suppl 2:S71-80. [PubMed:16336752]
Genbank
J00228
KEGG Drug
D03455
PubChem Substance
46507042
RxNav
318341
ChEMBL
CHEMBL1201577
Therapeutic Targets Database
DNC000788
PharmGKB
PA10040
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Cetuximab
AHFS Codes
  • 10:00.00 — Antineoplastic Agents
FDA label
Download (73.8 KB)
MSDS
Download (84.4 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
4Active Not RecruitingTreatmentMetastatic Colorectal Cancer (MCRC)1
4TerminatedTreatmentColorectal Cancers / Neoplasms Metastasis1
4TerminatedTreatmentNeoplasms, Head and Neck1
4Unknown StatusTreatmentHead and Neck Carcinoma1
4Unknown StatusTreatmentNeoplasms Metastasis / Neoplasms, Colorectal / Neoplasms, Hepatic1
3Active Not RecruitingTreatmentAdenocarcinoma of Lung Stage IV / Recurrent Large Cell Lung Carcinoma / Recurrent Lung Adenocarcinoma / Recurrent Squamous Cell Lung Carcinoma / Stage IV Large Cell Lung Carcinoma / Stage IV Squamous Cell Lung Carcinoma1
3Active Not RecruitingTreatmentBRAF V600E-mutant Metastatic Colorectal Cancer1
3Active Not RecruitingTreatmentCarcinoma, Colorectal1
3Active Not RecruitingTreatmentCarcinoma, Squamous Cell of Head and Neck1
3Active Not RecruitingTreatmentEsophageal Cancers1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
  • Cardinal Health
  • Catalent Pharma Solutions
  • ImClone Systems Inc.
  • Oso Biopharmaceuticals Manufacturing LLC
Dosage Forms
FormRouteStrength
Injection, solutionIntravenous5 mg/ml
Injection, solutionIntravenous; Parenteral5 MG/ML
SolutionIntravenous2 mg
SolutionIntravenous2 mg/1mL
Solution, concentrateIntravenous100 mg
Injection, solutionIntravenous100 mg/20ml
Injection, solutionIntravenous500 mg/100ml
Solution
Prices
Not Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)Region
CA1340417No1999-03-022016-03-02Canada flag
Additional Data Available
  • Filed On
    Filed On

    The date on which a patent was filed with the relevant government.

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Properties

State
Liquid
Experimental Properties
PropertyValueSource
melting point (°C)61 °C (FAB fragment), 71 °C (whole mAb)Vermeer, A.W.P. & Norde, W., Biophys. J. 78:394-404 (2000)
hydrophobicity-0.413Not Available
isoelectric point8.48Not 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. Hosokawa N, Yamamoto S, Uehara Y, Hori M, Tsuchiya KS: Effect of thiazinotrienomycin B, an ansamycin antibiotic, on the function of epidermal growth factor receptor in human stomach tumor cells. J Antibiot (Tokyo). 1999 May;52(5):485-90. [PubMed:10480573]
  2. Wakita H, Takigawa M: Activation of epidermal growth factor receptor promotes late terminal differentiation of cell-matrix interaction-disrupted keratinocytes. J Biol Chem. 1999 Dec 24;274(52):37285-91. [PubMed:10601294]
  3. Suwa T, Ueda M, Jinno H, Ozawa S, Kitagawa Y, Ando N, Kitajima M: Epidermal growth factor receptor-dependent cytotoxic effect of anti-EGFR antibody-ribonuclease conjugate on human cancer cells. Anticancer Res. 1999 Sep-Oct;19(5B):4161-5. [PubMed:10628369]
  4. Burke P, Schooler K, Wiley HS: Regulation of epidermal growth factor receptor signaling by endocytosis and intracellular trafficking. Mol Biol Cell. 2001 Jun;12(6):1897-910. [PubMed:11408594]
  5. Viloria-Petit A, Crombet T, Jothy S, Hicklin D, Bohlen P, Schlaeppi JM, Rak J, Kerbel RS: Acquired resistance to the antitumor effect of epidermal growth factor receptor-blocking antibodies in vivo: a role for altered tumor angiogenesis. Cancer Res. 2001 Jul 1;61(13):5090-101. [PubMed:11431346]
  6. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
General Function
Not Available
Specific Function
Receptor for the Fc region of immunoglobulins gamma. Low affinity receptor. Binds complexed or aggregated IgG and also monomeric IgG. Contrary to III-A, is not capable to mediate antibody-dependent...
Gene Name
FCGR3B
Uniprot ID
O75015
Uniprot Name
Low affinity immunoglobulin gamma Fc region receptor III-B
Molecular Weight
26215.64 Da
References
  1. Snyder LC, Astsaturov I, Weiner LM: Overview of monoclonal antibodies and small molecules targeting the epidermal growth factor receptor pathway in colorectal cancer. Clin Colorectal Cancer. 2005 Nov;5 Suppl 2:S71-80. [PubMed:16336752]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
General Function
Not Available
Specific Function
C1q associates with the proenzymes C1r and C1s to yield C1, the first component of the serum complement system. The collagen-like regions of C1q interact with the Ca(2+)-dependent C1r(2)C1s(2) proe...
Gene Name
C1QA
Uniprot ID
P02745
Uniprot Name
Complement C1q subcomponent subunit A
Molecular Weight
26016.47 Da
References
  1. Deveuve Q, Lajoie L, Barrault B, Thibault G: The Proteolytic Cleavage of Therapeutic Monoclonal Antibody Hinge Region: More Than a Matter of Subclass. Front Immunol. 2020 Feb 11;11:168. doi: 10.3389/fimmu.2020.00168. eCollection 2020. [PubMed:32117299]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
General Function
Not Available
Specific Function
C1q associates with the proenzymes C1r and C1s to yield C1, the first component of the serum complement system. The collagen-like regions of C1q interact with the Ca(2+)-dependent C1r(2)C1s(2) proe...
Gene Name
C1QB
Uniprot ID
P02746
Uniprot Name
Complement C1q subcomponent subunit B
Molecular Weight
26721.62 Da
References
  1. Deveuve Q, Lajoie L, Barrault B, Thibault G: The Proteolytic Cleavage of Therapeutic Monoclonal Antibody Hinge Region: More Than a Matter of Subclass. Front Immunol. 2020 Feb 11;11:168. doi: 10.3389/fimmu.2020.00168. eCollection 2020. [PubMed:32117299]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
General Function
Not Available
Specific Function
C1q associates with the proenzymes C1r and C1s to yield C1, the first component of the serum complement system. The collagen-like regions of C1q interact with the Ca(2+)-dependent C1r(2)C1s(2) proe...
Gene Name
C1QC
Uniprot ID
P02747
Uniprot Name
Complement C1q subcomponent subunit C
Molecular Weight
25773.56 Da
References
  1. Deveuve Q, Lajoie L, Barrault B, Thibault G: The Proteolytic Cleavage of Therapeutic Monoclonal Antibody Hinge Region: More Than a Matter of Subclass. Front Immunol. 2020 Feb 11;11:168. doi: 10.3389/fimmu.2020.00168. eCollection 2020. [PubMed:32117299]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
General Function
Not Available
Specific Function
Receptor for the Fc region of IgG. Binds complexed or aggregated IgG and also monomeric IgG. Mediates antibody-dependent cellular cytotoxicity (ADCC) and other antibody-dependent responses, such as...
Gene Name
FCGR3A
Uniprot ID
P08637
Uniprot Name
Low affinity immunoglobulin gamma Fc region receptor III-A
Molecular Weight
29088.895 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423]
  3. Zhang W, Gordon M, Schultheis AM, Yang DY, Nagashima F, Azuma M, Chang HM, Borucka E, Lurje G, Sherrod AE, Iqbal S, Groshen S, Lenz HJ: FCGR2A and FCGR3A polymorphisms associated with clinical outcome of epidermal growth factor receptor expressing metastatic colorectal cancer patients treated with single-agent cetuximab. J Clin Oncol. 2007 Aug 20;25(24):3712-8. [PubMed:17704420]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
General Function
Receptor signaling protein activity
Specific Function
High affinity receptor for the Fc region of immunoglobulins gamma. Functions in both innate and adaptive immune responses.
Gene Name
FCGR1A
Uniprot ID
P12314
Uniprot Name
High affinity immunoglobulin gamma Fc receptor I
Molecular Weight
42631.525 Da
References
  1. Negri DR, Tosi E, Valota O, Ferrini S, Cambiaggi A, Sforzini S, Silvani A, Ruffini PA, Colnaghi MI, Canevari S: In vitro and in vivo stability and anti-tumour efficacy of an anti-EGFR/anti-CD3 F(ab')2 bispecific monoclonal antibody. Br J Cancer. 1995 Oct;72(4):928-33. [PubMed:7547242]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
General Function
Not Available
Specific Function
Binds to the Fc region of immunoglobulins gamma. Low affinity receptor. By binding to IgG it initiates cellular responses against pathogens and soluble antigens. Promotes phagocytosis of opsonized ...
Gene Name
FCGR2A
Uniprot ID
P12318
Uniprot Name
Low affinity immunoglobulin gamma Fc region receptor II-a
Molecular Weight
35000.42 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423]
  3. Zhang W, Gordon M, Schultheis AM, Yang DY, Nagashima F, Azuma M, Chang HM, Borucka E, Lurje G, Sherrod AE, Iqbal S, Groshen S, Lenz HJ: FCGR2A and FCGR3A polymorphisms associated with clinical outcome of epidermal growth factor receptor expressing metastatic colorectal cancer patients treated with single-agent cetuximab. J Clin Oncol. 2007 Aug 20;25(24):3712-8. [PubMed:17704420]

Drug created on June 13, 2005 07:24 / Updated on September 27, 2020 08:17

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