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

作用方式

抑制剂

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

乳腺癌结直肠癌肝转移肝癌+ [2]

原研机构

Amgen, Inc.

在研机构-

非在研机构

Amgen Research (Munich) GmbH

Amgen, Inc.Merck Serono SA

权益机构-

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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结构/序列

Sequence Code 94529H

来源: *****

Sequence Code 211155L

来源: *****

关联

1

项与阿德木单抗相关的临床试验

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

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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20

项与阿德木单抗相关的文献（医药）

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.

2012-09-01·Annals of oncology : official journal of the European Society for Medical Oncology1区 · 医学

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

1区 · 医学

Article

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

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.

2010-12-01·INTERNATIONAL JOURNAL OF GYNECOLOGICAL CANCER

Primary cervical carcinoma cell lines overexpress epithelial cell adhesion molecule (EpCAM) and are highly sensitive to immunotherapy with MT201, a fully human monoclonal anti-EpCAM antibody.

Article

作者: Silasi, Dan-Arin ; Casagrande, Francesca ; Rutherford, Thomas J ; Bellone, Marta ; Cocco, Emiliano ; Richter, Christine E ; Pecorelli, Sergio ; Santin, Alessandro D ; Schwartz, Peter E ; Bellone, Stefania ; Rüttinger, Dominik ; Todeschini, Paola ; Azodi, Masoud

INTRODUCTION:

Epithelial cell adhesion molecule (EpCAM) is a surface glycoprotein highly differentially expressed in many epithelial malignancies. The goal of this study was to evaluate the expression of EpCAM and the potential of MT201 (adecatumumab), a human monoclonal antibody targeting EpCAM, against multiple primary cervical carcinoma cell lines.

METHODS:

Epithelial cell adhesion molecule expression was evaluated by real-time polymerase chain reaction and flow cytometry in a total of 8 primary cervical cancer cell lines. Sensitivity to MT201-mediated cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity was tested in standard 4-hour 51Cr release assays. To investigate the effect of interleukin-2 (IL-2) on MT201-mediated ADCC, 4-hour 51Cr release assays were also conducted in the presence of low doses of IL-2.

RESULTS:

High messenger RNA expression by real-time polymerase chain reaction and high EpCAM surface expression by flow cytometry were detected in 4 (50%) of 8 primary cervical carcinoma cell lines. With no exception, the primary cell lines derived from clinically aggressive tumors showed EpCAM overexpression. Whereas these cell lines were highly resistant to complement-dependent cytotoxicity and natural killer (NK)-dependent cytotoxicity in vitro (range of killing, 4%-19%), EpCAM-positive cell lines showed high sensitivity to MT201-mediated ADCC (range of killing, 23%-59%). Incubation with IL-2 in addition to MT201 significantly increased the cytotoxic activity against EpCAM-positive cervical cancer cell lines (P = 0.007). Addition of human serum also further increased the MT201-mediated killing of EpCAM-positive cell lines (P = 0.03).

CONCLUSIONS:

Epithelial cell adhesion molecule is highly expressed in primary cervical carcinoma cell lines, and these biologically aggressive tumors are highly sensitive to MT201-mediated cytotoxicity in vitro. MT201 may represent a novel, potentially highly effective treatment option for patients with cervical carcinoma, especially for those with advanced, recurrent, or metastatic disease refractory to standard salvage therapy.

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
结直肠癌肝转移	临床2期	法国	Amgen Research (Munich) GmbH	2009-03-01
结直肠癌肝转移	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	-	Amgen, Inc.	-
乳腺癌	临床2期	-	Merck Serono SA	-
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)	網壓鏇蓋製願醖淵鑰鹹(蓋夢製夢簾醖構鬱襯鹹) = 憲襯襯願夢選鹹淵選衊鏇遞艱網網夢襯鹽願積 (鹹獵齋艱餘網範壓鏇齋 )	-	2009-05-20
				MT201 (550 mg/m2)	網壓鏇蓋製願醖淵鑰鹹(蓋夢製夢簾醖構鬱襯鹹) = 淵築積網憲遞遞膚餘選鏇遞艱網網夢襯鹽願積 (鹹獵齋艱餘網範壓鏇齋 )
ASCO2007 人工标引	临床2期	转移性乳腺癌	109	adecatumumab (high-level EpCAM expression)	夢艱獵廠蓋顧蓋廠鹹憲(構遞製簾鏇淵淵構糧壓) = 糧顧製願網壓鏇構鑰築餘襯齋衊鬱構構選顧鹹 (鹽憲艱廠醖積窪餘簾壓 ) 更多	非优	2007-06-20
				adecatumumab (low-level EpCAM expression)	夢艱獵廠蓋顧蓋廠鹹憲(構遞製簾鏇淵淵構糧壓) = 窪醖壓衊構觸積遞襯廠餘襯齋衊鬱構構選顧鹹 (鹽憲艱廠醖積窪餘簾壓 )