阿德木单抗(Adecatumumab) - 药物靶点：EpCAM_专利_临床

概要

基本信息

药物类型

单克隆抗体

别名

Anti-EpCAM mAb MT201、Human anti-EpCAM monoclonal antibody MT201、Monoclonal antibody MT201

+ [3]

靶点

EpCAM

作用机制

EpCAM抑制剂(上皮细胞粘附分子抑制剂)、ADCC(抗体依赖的细胞毒作用)

治疗领域

肿瘤消化系统疾病皮肤和肌肉骨骼疾病+ [1]

在研适应症-

非在研适应症

乳腺癌结直肠癌肝癌+ [2]

原研机构

Amgen, Inc.

在研机构-

非在研机构

Amgen Research (Munich) GmbHMerck Serono SA

Amgen, Inc.

最高研发阶段无进展临床2期

首次获批日期-

最高研发阶段(中国)-

特殊审评-

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序列信息

Sequence Code 94529H

来源: *****

Sequence Code 211155L

来源: *****

关联

3

项与阿德木单抗相关的临床试验

EUCTR2008-004706-14-FR / Not yet recruiting临床2期

A randomized, open-label, controlled, multi-center Phase II study to evaluate the efficacy and safety of adecatumumab alone or sequentially to FOLFOX relative to FOLFOX after R0 resection of colorectal liver metastases

开始日期2009-04-30

申办/合作机构

Micromet AG

NCT00866944 / Completed临床2期

A Randomized, Open-label, Controlled, Multi-center Phase II Study to Evaluate the Efficacy and Safety of Adecatumumab Alone or Sequentially to FOLFOX Relative to FOLFOX After R0 Resection of Colorectal Liver Metastases

The purpose of this study is to determine the effect of adecatumumab alone or following FOLFOX in patients with R0 resected liver metastases from CRC (colorectal carcinoma) and to compare the effect to FOLFOX alone.

开始日期2009-03-01

申办/合作机构

Amgen Research (Munich) GmbH

EUCTR2008-004706-14-DE / Not yet recruitingN/A

A randomized, open-label, controlled, multi-center Phase II study to evaluate the efficacy and safety of adecatumumab alone or sequentially to FOLFOX relative to FOLFOX after R0 resection of colorectal liver metastases

开始日期2009-02-09

申办/合作机构

Micromet AG

100 项与阿德木单抗相关的临床结果

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100 项与阿德木单抗相关的转化医学

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100 项与阿德木单抗相关的专利（医药）

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27

项与阿德木单抗相关的文献（医药）

2023-02-01·Monoclonal antibodies in immunodiagnosis and immunotherapy

Epitope Mapping of an Anti-EpCAM Monoclonal Antibody (EpMab-37) Using the Alanine Scanning Method

Article

作者: Kaneko, Mika K. ; Yoshikawa, Takeo ; Kato, Yukinari ; Suzuki, Hiroyuki ; Tanaka, Tomohiro ; Asano, Teizo ; Li, Guanjie

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.

2019-04-09·Proceedings of the National Academy of Sciences of the United States of America1区 · 综合性期刊

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

1区 · 综合性期刊

Article

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

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.

2018-10-17·Current cancer drug targets4区 · 医学

Antibody Based EpCAM Targeted Therapy of Cancer, Review and Update

4区 · 医学

Review

作者: 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.

1

项与阿德木单抗相关的新闻（医药）

2007-08-30

·BioSpace

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:

合作抗体

100 项与阿德木单抗相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
-	阿德木单抗	-	DB05006

研发状态

10 条进展最快的记录,

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适应症	最高研发状态	国家/地区	公司	日期
结直肠癌	临床2期	法国	Amgen Research (Munich) GmbH	2009-03-01
结直肠癌	临床2期	德国	Amgen Research (Munich) GmbH	2009-03-01
肝癌	临床2期	法国	Amgen Research (Munich) GmbH	2009-03-01
肝癌	临床2期	德国	Amgen Research (Munich) GmbH	2009-03-01
肝转移	临床2期	法国	Amgen Research (Munich) GmbH	2009-03-01
肝转移	临床2期	德国	Amgen Research (Munich) GmbH	2009-03-01
乳腺癌	临床2期	-	Merck Serono SA	-
乳腺癌	临床2期	-	Amgen, Inc.	-
前列腺癌	临床2期	-	Amgen, Inc.	-
前列腺癌	临床2期	-	Merck Serono SA	-

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临床结果

适应症

分期

评价

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


ASCO2009	临床1期	转移性乳腺癌	22	MT201 (180 mg/m2)	壓糧範簾顧憲襯膚範顧(鬱構鹽淵齋壓餘積願鏇) = 衊壓艱鬱糧窪鬱觸壓築願艱鹹鹽襯齋願齋壓繭 (願遞憲蓋廠願鏇鏇積醖 )	-	2009-05-20
				MT201 (550 mg/m2)	壓糧範簾顧憲襯膚範顧(鬱構鹽淵齋壓餘積願鏇) = 壓鬱積網築願願範獵襯願艱鹹鹽襯齋願齋壓繭 (願遞憲蓋廠願鏇鏇積醖 )
ASCO2007 人工标引	临床2期	转移性乳腺癌	109	adecatumumab (high-level EpCAM expression)	鏇觸網網壓願醖憲窪壓(簾製蓋獵鹹廠艱簾選範) = 遞範繭製鬱壓遞鹽願鹹襯繭鹽簾範遞蓋遞積鏇 (夢顧夢鹽鹹選構醖構積 ) 更多	非优	2007-06-20
				adecatumumab (low-level EpCAM expression)	鏇觸網網壓願醖憲窪壓(簾製蓋獵鹹廠艱簾選範) = 壓繭製糧衊夢觸夢遞醖襯繭鹽簾範遞蓋遞積鏇 (夢顧夢鹽鹹選構醖構積 )