Identification

Name
Catumaxomab
Accession Number
DB06607
Type
Biotech
Groups
Approved, Investigational, Withdrawn
Biologic Classification
Protein Based Therapies
Monoclonal antibody (mAb)
Description

Catumaxumab is a trifunctional monoclonal antibody developed for use in cancer treatment. It has affinity for T-cells, accessory immune cells, and cancer cells. Catumaxumab was initially authorized for market by the European Medicines Agency in April 2009 for the treatment of malignant ascites [3]. Its market authorization was withdrawn in the EU in June 2017 at the manufacturer's request due to the company's insolvency. Catumaxumab was approved for market in Canada in May 2012 for the same condition [FDA Label]. It is currently available under the brand name Removab.

Protein structure
Db06607
Protein chemical formula
Not Available
Protein average weight
150511.0 Da (Intact Mass)
Sequences
Not Available
Synonyms
Not Available
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
RemovabSolution0.1 mgIntraperitonealFresenius Biotech GmbhNot applicableNot applicableCanada
RemovabSolution0.1 mgIntraperitonealFresenius Biotech GmbhNot applicableNot applicableCanada
Categories
UNII
M2HPV837HO
CAS number
509077-98-9

Pharmacology

Indication

For use in the management of malignant ascites tumours via intraperitoneal infusion where standard therapy is not available or feasible [FDA Label].

Structured Indications
Pharmacodynamics

Catumaxomab brings cancer cells, T cells, and accessory immune cells into close proximity and stimulates activation and of immune cells [FDA Label]. This facilitates immune system-mediated destruction of the cancer cells.

Mechanism of action

Catumaxomab contains epitopes for human CD3 and human epithelial cell adehesion molecule. It also has an intact immunoglobulin gamma constant region allowing it to bind to Fcγ I, IIa, and III receptors [FDA Label]. By binding to CD3 on killer T cells, EpCAM on cancer cells, and Fcγ receptors on accessory immune cells like macrophages and NK cells, Catumaxomab brings immune cells into close proximity to EpCAM positive cancer cells. As a functional antibody, Catumaxomab also stimulates bound NK cells to release cytotoxic mediators like granzyme or bound macrophages to phagocytose the cancer cell. Phagocytosed cancer cells can be processed and have their antigens presented on major histocompatibililty complex II to activate helper T cells and contribute to humoural immunity and activation of killer T cells against EpCAM postive cancer cells. These macrophages also release inflammatory cytokines to attract additional immune cells to EpCAM positive tissues. When antibodies reach higher concentrations, they can stimulate complement-mediated cytotoxicity against EpCAM positive cancer cells. Bound killer T cells are activated resulting in proliferation and release of cytotoxic mediators resulting in antibody-dependent cell-mediated cytotoxicity against the cancer cell.

TargetActionsOrganism
NEpithelial cell adhesion molecule
ligand
Human
ALow affinity immunoglobulin gamma Fc region receptor II-a
agonist
Human
ALow affinity immunoglobulin gamma Fc region receptor III-A
agonist
Human
ALow affinity immunoglobulin gamma Fc region receptor III-B
agonist
Human
AT-cell surface glycoprotein CD3 epsilon chain
agonist
Human
AHigh affinity immunoglobulin gamma Fc receptor I
agonist
Human
Absorption

Catumaxomab has an observed bioavailability of 82% [2]. This value decreases as the EpCAM positive tumour load and number of immune cells in the peritoneal cavity increases. While some Catumaxomab escapes into systemic circulation, most localizes to EpCAM positive tissues. Tmax is 19 h.

Volume of distribution
Not Available
Protein binding
Not Available
Metabolism
Not Available
Route of elimination
Not Available
Half life

Catumaxomab has an apparent half life of elimination of 2.5 days [FDA Label].

Clearance
Not Available
Toxicity

As a mouse/rat hybrid antibody, Catumaxomab can produce immunogenicity in other species [1]. No acute toxicity was found in mice using an analog with an anti-mouse CD3 paratope in place of Catumaxomab's anti-human CD3 paratope. A transient decrease in serum leukocytes has been observed but is attributed to migration of immune cells into EpCAM positive tissues. Data specific to Catumaxomab is extremely limited as its specificity for human protein requires data from human subjects [FDA Label].

Affected organisms
  • Humans
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteractionDrug group
AcetyldigitoxinAcetyldigitoxin may decrease the cardiotoxic activities of Catumaxomab.Approved
AcetyldigoxinAcetyldigoxin may decrease the cardiotoxic activities of Catumaxomab.Experimental
AncestimThe risk or severity of cytotoxicity can be increased when Ancestim is combined with Catumaxomab.Approved, Investigational, Withdrawn
Anthrax immune globulin humanThe therapeutic efficacy of Anthrax immune globulin human can be decreased when used in combination with Catumaxomab.Approved
Bacillus calmette-guerin substrain connaught live antigenThe therapeutic efficacy of Bacillus calmette-guerin substrain connaught live antigen can be decreased when used in combination with Catumaxomab.Approved, Investigational
Bacillus calmette-guerin substrain tice live antigenThe therapeutic efficacy of Bacillus calmette-guerin substrain tice live antigen can be decreased when used in combination with Catumaxomab.Approved
BCG vaccineThe therapeutic efficacy of BCG vaccine can be decreased when used in combination with Catumaxomab.Investigational
BelimumabThe risk or severity of adverse effects can be increased when Catumaxomab is combined with Belimumab.Approved
BevacizumabBevacizumab may increase the cardiotoxic activities of Catumaxomab.Approved, Investigational
CabazitaxelThe risk or severity of adverse effects can be increased when Cabazitaxel is combined with Catumaxomab.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 Catumaxomab.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 Catumaxomab.Approved
CyclophosphamideCyclophosphamide may increase the cardiotoxic activities of Catumaxomab.Approved, Investigational
CymarinCymarin may decrease the cardiotoxic activities of Catumaxomab.Experimental
DeslanosideDeslanoside may decrease the cardiotoxic activities of Catumaxomab.Approved
DigitoxinDigitoxin may decrease the cardiotoxic activities of Catumaxomab.Approved, Investigational
DigoxinDigoxin may decrease the cardiotoxic activities of Catumaxomab.Approved
Digoxin Immune Fab (Ovine)Digoxin Immune Fab (Ovine) may decrease the cardiotoxic activities of Catumaxomab.Approved
DocetaxelThe risk or severity of adverse effects can be increased when Docetaxel is combined with Catumaxomab.Approved, Investigational
G17DTThe therapeutic efficacy of G17DT can be decreased when used in combination with Catumaxomab.Investigational
GI-5005The therapeutic efficacy of GI-5005 can be decreased when used in combination with Catumaxomab.Investigational
GitoformateGitoformate may decrease the cardiotoxic activities of Catumaxomab.Experimental
Hepatitis A VaccineThe therapeutic efficacy of Hepatitis A Vaccine can be decreased when used in combination with Catumaxomab.Approved
Hepatitis B Vaccine (Recombinant)The therapeutic efficacy of Hepatitis B Vaccine (Recombinant) can be decreased when used in combination with Catumaxomab.Approved, Withdrawn
Human rabies virus immune globulinThe therapeutic efficacy of Human rabies virus immune globulin can be decreased when used in combination with Catumaxomab.Approved
INGN 201The therapeutic efficacy of INGN 201 can be decreased when used in combination with Catumaxomab.Investigational
INGN 225The therapeutic efficacy of INGN 225 can be decreased when used in combination with Catumaxomab.Investigational
Japanese encephalitis virus strain sa 14-14-2 antigen (formaldehyde inactivated)The therapeutic efficacy of Japanese encephalitis virus strain sa 14-14-2 antigen (formaldehyde inactivated) can be decreased when used in combination with Catumaxomab.Approved
Lanatoside CLanatoside C may decrease the cardiotoxic activities of Catumaxomab.Experimental
MetildigoxinMetildigoxin may decrease the cardiotoxic activities of Catumaxomab.Experimental
OleandrinOleandrin may decrease the cardiotoxic activities of Catumaxomab.Experimental, Investigational
OuabainOuabain may decrease the cardiotoxic activities of Catumaxomab.Approved
PaclitaxelThe risk or severity of adverse effects can be increased when Paclitaxel is combined with Catumaxomab.Approved, Vet Approved
PeruvosidePeruvoside may decrease the cardiotoxic activities of Catumaxomab.Experimental
ProscillaridinProscillaridin may decrease the cardiotoxic activities of Catumaxomab.Experimental
Rabies virus inactivated antigen, AThe therapeutic efficacy of Rabies virus inactivated antigen, A can be decreased when used in combination with Catumaxomab.Approved, Investigational
RindopepimutThe therapeutic efficacy of Rindopepimut can be decreased when used in combination with Catumaxomab.Investigational
Rotavirus VaccineThe therapeutic efficacy of Rotavirus Vaccine can be decreased when used in combination with Catumaxomab.Approved
Rubella virus vaccineThe therapeutic efficacy of Rubella virus vaccine can be decreased when used in combination with Catumaxomab.Approved, Investigational
Salmonella typhi ty2 vi polysaccharide antigenThe therapeutic efficacy of Salmonella typhi ty2 vi polysaccharide antigen can be decreased when used in combination with Catumaxomab.Approved
Salmonella typhi ty21a live antigenThe therapeutic efficacy of Salmonella typhi ty21a live antigen can be decreased when used in combination with Catumaxomab.Approved
SRP 299The therapeutic efficacy of SRP 299 can be decreased when used in combination with Catumaxomab.Investigational
TecemotideThe therapeutic efficacy of Tecemotide can be decreased when used in combination with Catumaxomab.Investigational
TG4010The therapeutic efficacy of TG4010 can be decreased when used in combination with Catumaxomab.Investigational
TrastuzumabTrastuzumab may increase the cardiotoxic activities of Catumaxomab.Approved, Investigational
Varicella Zoster Vaccine (Live/Attenuated)The therapeutic efficacy of Varicella Zoster Vaccine (Live/Attenuated) can be decreased when used in combination with Catumaxomab.Approved
Yellow Fever VaccineThe therapeutic efficacy of Yellow Fever Vaccine can be decreased when used in combination with Catumaxomab.Approved, Investigational
Food Interactions
Not Available

References

Synthesis Reference

Seimetz D, Lindhofer H, Bokemeyer C. Development and approval of the trifunctional antibody catumaxomab (anti-EpCAM x anti-CD3) as a targeted cancer immunotherapy. Cancer Treat Rev. 2010;36(6):458-67.

Lindhofer H, Mocikat R, Steipe B, Thierfelder S. Preferential species-restricted heavy/light chain pairing in rat/mouse quadromas. Implications for a single-step purification of bispecific antibodies. J Immunol. 1995;155(1):219-25.

General References
  1. Seimetz D, Lindhofer H, Bokemeyer C: Development and approval of the trifunctional antibody catumaxomab (anti-EpCAM x anti-CD3) as a targeted cancer immunotherapy. Cancer Treat Rev. 2010 Oct;36(6):458-67. doi: 10.1016/j.ctrv.2010.03.001. Epub 2010 Mar 27. [PubMed:20347527]
  2. Ruf P, Kluge M, Jager M, Burges A, Volovat C, Heiss MM, Hess J, Wimberger P, Brandt B, Lindhofer H: Pharmacokinetics, immunogenicity and bioactivity of the therapeutic antibody catumaxomab intraperitoneally administered to cancer patients. Br J Clin Pharmacol. 2010 Jun;69(6):617-25. doi: 10.1111/j.1365-2125.2010.03635.x. [PubMed:20565453]
  3. EMA: Removab Withdrawal from Market [Link]
External Links
Wikipedia
Catumaxomab
ATC Codes
L01XC09 — Catumaxomab
AHFS Codes
  • 10:00.00 — Antineoplastic Agents
FDA label
Download (394 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1TerminatedTreatmentEpithelial Cancer Patients1
2CompletedTreatmentAbdominal wall neoplasm / Cancer of the Ovary / Fallopian Tube Neoplasms1
2CompletedTreatmentCancer of the Ovary2
2CompletedTreatmentCancer of the Ovary / Ovarian Epithelial Cancer1
2CompletedTreatmentGastric Adenocarcinoma With Peritoneal Carcinomatosis / Siewert Type II Adenocarcinoma of Esophagogastric Junction With Peritoneal Carcinomatosis / Siewert Type III Adenocarcinoma of Esophagogastric Junction With Peritoneal Carcinomatosis1
2CompletedTreatmentGastric Adenocarcinoma / Malignant Neoplasm of Stomach2
2CompletedTreatmentMalignant Ascites1
2CompletedTreatmentMalignant Ascites Due to Epithelial Carcinoma1
2CompletedTreatmentRecurrent Epithelial Ovarian Cancer1
2TerminatedTreatmentPatients With Gastric Peritoneal Carcinomatosis1
2, 3CompletedTreatmentEpCam Positive Tumor (e.g.Ovarian, Gastric, Colon, Breast) / Malignant Ascites1
3CompletedTreatmentCancers / Carcinoma NOS / Malignant Ascites / Neoplasms1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
FormRouteStrength
SolutionIntraperitoneal0.1 mg
Prices
Not Available
Patents
Not Available

Properties

State
Solid
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
No
Actions
Ligand
General Function
Protein complex binding
Specific Function
May act as a physical homophilic interaction molecule between intestinal epithelial cells (IECs) and intraepithelial lymphocytes (IELs) at the mucosal epithelium for providing immunological barrier...
Gene Name
EPCAM
Uniprot ID
P16422
Uniprot Name
Epithelial cell adhesion molecule
Molecular Weight
34932.005 Da
References
  1. Seimetz D, Lindhofer H, Bokemeyer C: Development and approval of the trifunctional antibody catumaxomab (anti-EpCAM x anti-CD3) as a targeted cancer immunotherapy. Cancer Treat Rev. 2010 Oct;36(6):458-67. doi: 10.1016/j.ctrv.2010.03.001. Epub 2010 Mar 27. [PubMed:20347527]
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Agonist
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. Seimetz D, Lindhofer H, Bokemeyer C: Development and approval of the trifunctional antibody catumaxomab (anti-EpCAM x anti-CD3) as a targeted cancer immunotherapy. Cancer Treat Rev. 2010 Oct;36(6):458-67. doi: 10.1016/j.ctrv.2010.03.001. Epub 2010 Mar 27. [PubMed:20347527]
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Agonist
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. Seimetz D, Lindhofer H, Bokemeyer C: Development and approval of the trifunctional antibody catumaxomab (anti-EpCAM x anti-CD3) as a targeted cancer immunotherapy. Cancer Treat Rev. 2010 Oct;36(6):458-67. doi: 10.1016/j.ctrv.2010.03.001. Epub 2010 Mar 27. [PubMed:20347527]
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Agonist
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. Seimetz D, Lindhofer H, Bokemeyer C: Development and approval of the trifunctional antibody catumaxomab (anti-EpCAM x anti-CD3) as a targeted cancer immunotherapy. Cancer Treat Rev. 2010 Oct;36(6):458-67. doi: 10.1016/j.ctrv.2010.03.001. Epub 2010 Mar 27. [PubMed:20347527]
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Agonist
General Function
Transmembrane signaling receptor activity
Specific Function
The CD3 complex mediates signal transduction, resulting in T cell activation and proliferation. Required for normal immune responses (PubMed:15546002, PubMed:8490660).
Gene Name
CD3E
Uniprot ID
P07766
Uniprot Name
T-cell surface glycoprotein CD3 epsilon chain
Molecular Weight
23147.09 Da
References
  1. Seimetz D, Lindhofer H, Bokemeyer C: Development and approval of the trifunctional antibody catumaxomab (anti-EpCAM x anti-CD3) as a targeted cancer immunotherapy. Cancer Treat Rev. 2010 Oct;36(6):458-67. doi: 10.1016/j.ctrv.2010.03.001. Epub 2010 Mar 27. [PubMed:20347527]
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Agonist
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. Seimetz D, Lindhofer H, Bokemeyer C: Development and approval of the trifunctional antibody catumaxomab (anti-EpCAM x anti-CD3) as a targeted cancer immunotherapy. Cancer Treat Rev. 2010 Oct;36(6):458-67. doi: 10.1016/j.ctrv.2010.03.001. Epub 2010 Mar 27. [PubMed:20347527]

Drug created on March 19, 2008 10:40 / Updated on April 23, 2018 23:10