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, Monoclonal antibody MT201

+ [3]

Target

EpCAM

Action

inhibitors

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 Liver MetastasesLiver metastases+ [1]

Originator Organization

Amgen, Inc.

Active Organization-

Inactive Organization

Amgen Research (Munich) GmbH

Amgen, Inc.Merck Serono SA

License Organization-

Drug Highest PhasePendingPhase 2

First Approval Date-

Regulation-

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Structure/Sequence

Sequence Code 94529H

Source: *****

Sequence Code 211155L

Source: *****

Near‐infrared photoimmunotherapy (NIR‐PIT) is a tumor‐specific treatment using monoclonal antibody (mAb) photosensitizer conjugates, followed by near‐infrared light irradiation. This study aimed to identify the optimum target for treating esophagogastric junction (EGJ) adenocarcinoma and to evaluate the efficacy of NIR‐PIT using mAbs in preclinical models. Tumor samples from 46 consecutive patients who had undergone surgery without any prior treatment for EGJ adenocarcinoma were assessed for expression and homogeneity of epidermal growth factor receptor (EGFR), human epidermal growth factor receptor 2 (HER2), and epithelial cell adhesion molecule (EpCAM) through immunohistochemistry. Results showed positive rates of 22%, 13%, and 98% for EGFR, HER2, and EpCAM, respectively, with EpCAM also demonstrating the highest homogeneity (93%). Therefore, EpCAM was selected as the optimal target for NIR‐PIT. The fully human monoclonal antibody targeting EpCAM, adecatumumab, was conjugated with the photosensitizer IR700 at different dye‐antibody ratios (DAR2, DAR4, DAR7) and tested on OE19 cells and xenograft mouse models under near‐infrared light irradiation. NIR‐PIT with adecatumumab‐IR700 significantly reduced tumor size and improved prognoses compared to controls, with DAR2 showing the best balance of efficacy and minimal side effects. Notable EpCAM expression and homogeneity underpin EpCAM as a promising target for NIR‐PIT in EGJ adenocarcinoma. The fully human anti‐EpCAM antibody may be suitable for NIR‐PIT in EGJ adenocarcinoma.

17 Oct 2018·Current cancer drug targetsQ4 · MEDICINE

Antibody Based EpCAM Targeted Therapy of Cancer, Review and Update

Q4 · MEDICINE

Review

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

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.

01 Sep 2012·Annals of oncology : official journal of the European Society for Medical OncologyQ1 · MEDICINE

Phase IB study of the EpCAM antibody adecatumumab combined with docetaxel in patients with EpCAM-positive relapsed or refractory advanced-stage breast cancer

Q1 · MEDICINE

Article

Author: C. Wolf ; D. Oruzio ; M. Schuler ; C.A. Hanusch ; M. Schmidt ; M. Sebastian ; A. Wolf ; N. Marschner ; G. Schlimok ; G. Göppel ; D. Rüttinger ; G.G. Steger ; A. Lang ; W. Eiermann ; P.A. Baeuerle

BACKGROUND:

Targeted therapy options in HER2-negative breast cancer are limited. This open-label, multicenter phase IB dose-escalation trial was conducted to determine safety, tolerability, and antitumor activity of a combination of docetaxel (Taxotere) and increasing doses of adecatumumab, a human IgG1 antibody targeting epithelial cell adhesion molecule (EpCAM), in EpCAM-positive relapsed or primary refractory advanced-stage breast cancer.

PATIENTS AND METHODS:

Patients pretreated with up to four prior chemotherapy regimens received increasing adecatumumab doses either every 3 weeks (q3w) or weekly (qw) combined with docetaxel (100 mg/m² q3w). Primary end points were safety and tolerability. Antitumor activity was evaluated according to RECIST. Clinical benefit was defined as complete or partial response or stable disease for ≥24 weeks.

RESULTS:

Thirty-one evaluable patients were treated. Most adverse events were mild to moderate in severity. Neutropenia, leukocytopenia, lymphopenia, and diarrhea (dose-limiting) were the most frequent toxic effects. Maximum tolerated doses of adecatumumab given in combination with docetaxel were 550 mg/m² q3w and 360 mg/m² qw. Clinical benefit was observed in 44% of patients treated with q3w adecatumumab and docetaxel, increasing to 63% in patients with high EpCAM-expressing tumors.

CONCLUSION:

Combination therapy of adecatumumab and docetaxel is safe, feasible, and potentially active in heavily pretreated advanced-stage breast cancer.

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 Liver Metastases	Phase 2	France	Amgen Research (Munich) GmbH	01 Mar 2009
Colorectal Liver Metastases	Phase 2	Germany	Amgen Research (Munich) GmbH	01 Mar 2009
Liver metastases	Phase 2	France	Amgen Research (Munich) GmbH	01 Mar 2009
Liver metastases	Phase 2	Germany	Amgen Research (Munich) GmbH	01 Mar 2009
Breast Cancer	Phase 2	-	Amgen, Inc.	-
Breast Cancer	Phase 2	-	Merck Serono SA	-
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)	fdpmupeeuj(xvpkvwqegv) = sewwpezcjc txbczxfqvp (axvwfnbaso )	-	20 May 2009
				MT201 (550 mg/m2)	fdpmupeeuj(xvpkvwqegv) = twofnmzerd txbczxfqvp (axvwfnbaso )
ASCO2007 Manual	Phase 2	Metastatic breast cancer	109	adecatumumab (high-level EpCAM expression)	sdimtnyiwi(vqabqykxwk) = ihqvfayuix lkmghboyqj (fhcvfzyzay ) View more	Non-superior	20 Jun 2007
				adecatumumab (low-level EpCAM expression)	sdimtnyiwi(vqabqykxwk) = wnjurkqfkv lkmghboyqj (fhcvfzyzay )
ASCO2004	Phase 1	Castration-Resistant Prostatic Cancer	20	MT201	edgughhkgf(zzegfjdovg) = itrkgfhmtd gbomwecmpy (kofezbmmfn )	-	15 Jul 2004

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