Delving into the Latest Updates on Adecatumumab with Synapse

Overview

Basic Info

Drug Type

Monoclonal antibody

Synonyms

Anti-EpCAM mAb MT201, Human anti-EpCAM monoclonal antibody MT201, MT201 antibody

+ [3]

Target

EpCAM

Mechanism

EpCAM inhibitors(Epithelial cell adhesion molecule inhibitors), ADCC(Antibody-dependent cell-mediated cytotoxicity (ADCC) effects)

Therapeutic Areas

NeoplasmsDigestive System DisordersSkin and Musculoskeletal Diseases+ [1]

Active Indication-

Inactive Indication

Breast CancerColorectal CancerLiver Cancer+ [2]

Originator Organization

Amgen, Inc.

Active Organization-

Inactive Organization

Amgen Research (Munich) GmbHMerck Serono SA

Amgen, Inc.

Drug Highest PhasePendingPhase 2

First Approval Date-

Regulation-

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Gene Sequence

Sequence Code 94529H

Source: *****

Sequence Code 211155L

Source: *****

The epithelial cell adhesion molecule (EpCAM) is a type I transmembrane glycoprotein, and plays critical roles in cell adhesion, proliferation, and tumorigenesis. EpCAM has been considered as a promising target for tumor diagnosis and therapy. Anti-EpCAM monoclonal antibodies (mAbs) have been developed for EpCAM-overexpressed tumors, and several clinical trials have demonstrated promising outcomes. We previously established an anti-EpCAM mAb, EpMab-37 (mouse IgG₁, kappa), using the Cell-Based Immunization and Screening method. EpMab-37 was revealed to recognize the conformational epitope of EpCAM. In this study, we determined the critical epitope of EpMab-37 by flow cytometry using the 1 × alanine scanning (1 × Ala-scan) and the 2 × alanine scanning (2 × Ala-scan) method. We first performed flow cytometry by 1 × Ala-scan using one alanine (or glycine)-substituted EpCAM mutants, which were expressed on Chinese hamster ovary-K1 cells, and found that the EpMab-37 did not recognize the R163A mutant of EpCAM. We next performed flow cytometry by 2 × Ala-scan using two alanine (or glycine) residues-substituted EpCAM mutants, and confirmed that EpMab-37 did not recognize R163A-including mutants of EpCAM. The results indicated that the critical binding epitope of EpMab-37 includes Arg163 of EpCAM.

09 Apr 2019·Proceedings of the National Academy of SciencesQ1 · CROSS-FIELD

MM-131, a bispecific anti-Met/EpCAM mAb, inhibits HGF-dependent and HGF-independent Met signaling through concurrent binding to EpCAM

Q1 · CROSS-FIELD

Article

Author: Schoeberl, Birgit ; Chattopadhyay, Shrikanta ; Maiwald, Tim ; Fulgham, Aaron ; Lugovskoy, Alexey A. ; Kearns, Jeffrey D. ; Logan, Derek T. ; Geddie, Melissa L. ; Masson, Kristina ; Kalra, Ashish ; Harms, Brian D. ; Casaletto, Jessica B. ; Welin, Martin ; Håkansson, Maria ; MacBeath, Gavin ; Su, Stephen ; Razlog, Maja ; Boudot, Antoine ; Nielsen, Ulrik B. ; Abu-Yousif, Adnan O. ; Kohli, Neeraj ; Raue, Andreas

Activation of the Met receptor tyrosine kinase, either by its ligand, hepatocyte growth factor (HGF), or via ligand-independent mechanisms, such as MET amplification or receptor overexpression, has been implicated in driving tumor proliferation, metastasis, and resistance to therapy. Clinical development of Met-targeted antibodies has been challenging, however, as bivalent antibodies exhibit agonistic properties, whereas monovalent antibodies lack potency and the capacity to down-regulate Met. Through computational modeling, we found that the potency of a monovalent antibody targeting Met could be dramatically improved by introducing a second binding site that recognizes an unrelated, highly expressed antigen on the tumor cell surface. Guided by this prediction, we engineered MM-131, a bispecific antibody that is monovalent for both Met and epithelial cell adhesion molecule (EpCAM). MM-131 is a purely antagonistic antibody that blocks ligand-dependent and ligand-independent Met signaling by inhibiting HGF binding to Met and inducing receptor down-regulation. Together, these mechanisms lead to inhibition of proliferation in Met-driven cancer cells, inhibition of HGF-mediated cancer cell migration, and inhibition of tumor growth in HGF-dependent and -independent mouse xenograft models. Consistent with its design, MM-131 is more potent in EpCAM-high cells than in EpCAM-low cells, and its potency decreases when EpCAM levels are reduced by RNAi. Evaluation of Met, EpCAM, and HGF levels in human tumor samples reveals that EpCAM is expressed at high levels in a wide range of Met-positive tumor types, suggesting a broad opportunity for clinical development of MM-131.

17 Oct 2018·Current Cancer Drug TargetsQ4 · MEDICINE

Antibody Based EpCAM Targeted Therapy of Cancer, Review and Update

Q4 · MEDICINE

Review

Author: Bandehpour, Mojghan ; Dastmalchi, Siavoush ; Zarredar, Habib ; Farajnia, Safar ; Kanipour, Farzad ; Eyvazi, Shirin

Todays, after four decades from the discovery of monoclonal antibodies by Kohler and Milstein in 1975, a dozen of antibodies are used in cancer targeted therapy with different strategies. The success of these antibodies depends on the specificity of antigens expressed on the cancer cells. Epithelial Cell Adhesion Molecule (EpCAM), a homophilic cell-cell adhesion glycoprotein is a well- known tumor antigen, which expresses on epithelial tumors and circulating tumor cells as well as cancer stem cells. The EpCAM signaling pathway is associated with proliferation, differentiation and adhesion of epithelial cancer cells. Here we review EpCAM structure, expression profile and its signaling pathway in cancer cells. In addition, we focused on structure, mechanism of action and success of anti EpCAM antibodies which have been used in different clinical trials. Based on literatures, Edrecolomab showed limited efficacy in the phase III studies. The wholly human monoclonal antibody Adecatumumab is dose- and target-dependent in metastatic breast cancer patients expressing EpCAM. The chimeric antibody, Catumaxomab, has been approved for the treatment of malignant ascites; however, this Mab showed considerable results in intrapleural administration in cancer patients. Anti EpCAM toxin conjugated antibodies like, Oportuzumab Monatox (scFv antibody and Pseudomonas exotoxin A (ETA)), Citatuzumab Bogatox (Fab fragment with bouganin toxin) and immono-conjugate antibody Tucotuzumab (monoclonal antibody with IL2), have shown acceptable results in different clinical trials. Almost, all of the antibodies were well-tolerated; however, still more clinical trials are needed for the approval of antibodies for the treatment of specific tumors.

1

News (Medical) associated with Adecatumumab

30 Aug 2007

·www.biospace.com

Micromet to Present at the Sal. Oppenheim 2nd European Healthcare Conference

BETHESDA, Md., Aug. 30 /PRNewswire-FirstCall/ -- Micromet, Inc. , a biopharmaceutical company focusing on the development of novel, proprietary antibody-based products for cancer, inflammation and autoimmune diseases, today announced that Dr. Christian Itin, President and Chief Executive Officer of Micromet, will present at the Sal. Oppenheim 2nd European Healthcare Conference in Frankfurt, Germany on Wednesday, September 5, 2007 at 9:50am Eastern time (3:50pm central European time). About Micromet, Inc. ( ) Micromet, Inc. is a biopharmaceutical company focusing on the development of novel, proprietary antibody-based products for cancer, inflammation and autoimmune diseases. Three product candidates are currently in clinical trials. MT103, also known as MEDI-538, is the first product candidate based on Micromet's novel BiTE(R) antibody product development platform and is being evaluated in a phase 1 clinical trial for the treatment of patients with non- Hodgkin's lymphoma. The BiTE antibody product development platform is based on a unique, antibody-based class of drugs that leverages the cytotoxic potential of T cells in the treatment of cancer. T cells are the most powerful 'killer cells' of the human immune system. Micromet has established a collaboration with MedImmune, Inc. for MT103/MEDI-538. The second clinical stage product candidate is adecatumumab, also known as MT201, a recombinant human monoclonal antibody which targets EpCAM expressing tumors. Adecatumumab is being developed for the treatment of patients with breast cancer. A phase 2a clinical trial in this indication has been completed and a phase 1b trial evaluating the safety and tolerability of MT201 in combination with docetaxel is currently ongoing in patients with metastatic breast cancer. Our third clinical stage product candidate is D93, also known as TRC093, a first-in- class humanized monoclonal antibody that inhibits angiogenesis and tumor cell growth by binding cleaved collagen. This product candidate is in phase 1 clinical trials and is being developed by TRACON Pharmaceuticals for the treatment of patients with cancer and age-related macular degeneration pursuant to license agreement under which Micromet has granted TRACON the worldwide rights to develop and commercialize D93/TRC093. In addition, Micromet has established a collaboration with Nycomed for the development and commercialization of MT203, Micromet's human antibody neutralizing the activity of granulocyte/macrophage colony stimulating factor (GM-CSF), which has potential applications in the treatment of inflammatory diseases, such as rheumatoid arthritis, as well as autoimmune diseases. Micromet, Inc. CONTACT: Christopher Schnittker, SVP & CFO, Micromet, Inc.,+1-240-752-1421, cschnittker@micromet-inc.com, Investors, Susan Noonan,+1-212-966-3650, susan@sanoonan.com, Patricia Garrison, +1-917-322-2567,pgarrison@rxir.com Web site:

CollaborateAntibody

100 Deals associated with Adecatumumab

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External Link

KEGG	Wiki	ATC	Drug Bank
-	Adecatumumab	-	DB05006

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Colorectal Cancer	Phase 2	DE	Amgen Research (Munich) GmbH	01 Mar 2009
Colorectal Cancer	Phase 2	FR	Amgen Research (Munich) GmbH	01 Mar 2009
Liver Cancer	Phase 2	FR	Amgen Research (Munich) GmbH	01 Mar 2009
Liver Cancer	Phase 2	DE	Amgen Research (Munich) GmbH	01 Mar 2009
Liver metastases	Phase 2	DE	Amgen Research (Munich) GmbH	01 Mar 2009
Liver metastases	Phase 2	FR	Amgen Research (Munich) GmbH	01 Mar 2009
Breast Cancer	Phase 2	-	Merck Serono SA	-
Breast Cancer	Phase 2	-	Amgen, Inc.	-
Prostatic Cancer	Phase 2	-	Amgen, Inc.	-
Prostatic Cancer	Phase 2	-	Merck Serono SA	-

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


ASCO2009	Phase 1	Metastatic breast cancer	22	MT201 (180 mg/m2)	(gungvlmrzq) = kwyhtyteop ehxnwpovdb (yrnmhsvmlh )	-	20 May 2009
				MT201 (550 mg/m2)	(gungvlmrzq) = rsensqvejy ehxnwpovdb (yrnmhsvmlh )
ASCO2007 Manual	Phase 2	Metastatic breast cancer	109	adecatumumab (high-level EpCAM expression)	(ppbphhisgr) = evrjnwnoqc lzydwvirla (ugkoyvheob ) View more	Non-superior	20 Jun 2007
				adecatumumab (low-level EpCAM expression)	(ppbphhisgr) = usztnxgufz lzydwvirla (ugkoyvheob )