英妥木单抗(Intetumumab) - 药物靶点：CD51_专利_临床

概要

基本信息

药物类型

单克隆抗体

别名

Intetumumab (USAN/INN)、CNTO 095、CNTO-095

+ [1]

靶点

CD51

作用机制

CD51拮抗剂(整合素α-V拮抗剂)

治疗领域

肿瘤皮肤和肌肉骨骼疾病泌尿生殖系统疾病

在研适应症-

非在研适应症

恶性黑色素瘤IV期黑色素瘤前列腺癌

原研机构

Janssen Global Services LLC

在研机构-

非在研机构

Ajinomoto Althea, Inc.Centocor, Inc.

Janssen Biotech, Inc.

+ [2]

最高研发阶段终止临床2期

首次获批日期-

最高研发阶段(中国)终止

特殊审评-

序列信息

Sequence Code 1052166H

来源: *****

Sequence Code 1052172L

来源: *****

关联

3

项与英妥木单抗相关的临床试验

NCT00888043 / Completed临床1期IIT

A Phase I/Biomarker Study of Bevacizumab in Combination With CNTO 95 in Patients With Refractory Solid Tumors

The purpose of this research study is to find out what side effects the combination of the two study drugs, bevacizumab (Avastin) and CNTO 95 have on the body and to determine the highest dose of CNTO 95 that can be given with bevacizumab that is safe and well tolerated.

开始日期2009-03-01

申办/合作机构

Centocor, Inc.

[+1]

NCT00537381 / Completed临床2期

A Randomized, Double-blind, Multicenter, Phase 2 Study of a Human Monoclonal Antibody to Human av Integrins (CNTO 95) in Combination With Docetaxel for the First-Line Treatment of Subjects With Metastatic Hormone Refractory Prostate Cancer

The purpose of this study is to assess the effects of intetumumab when given in combination with docetaxel and prednisone to participants with metastatic (spread of cancer cells from one part of the body to another) hormone-refractory (not responding to treatment) prostate cancer (abnormal tissue that grows and spreads in the body until it kills).

开始日期2007-05-01

申办/合作机构

Centocor, Inc.

NCT00246012 / Completed临床1/2期

A Phase 1/2, Multi-Center, Blinded, Randomized, Controlled Study of the Safety and Efficacy of the Human Monoclonal Antibody to Human α ν Integrins (CNTO 95), Alone and in Combination With Dacarbazine, in Subjects With Stage IV Melanoma

The purpose of this study is to evaluate the safety and effectiveness of the intetumumab, alone and in combination with dacarbazine, in patients with stage 4 melanoma.

开始日期2005-05-01

申办/合作机构

Centocor, Inc.

100 项与英妥木单抗相关的临床结果

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100 项与英妥木单抗相关的转化医学

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100 项与英妥木单抗相关的专利（医药）

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24

项与英妥木单抗相关的文献（医药）

2018-09-01·Journal of cancer research and clinical oncology3区 · 医学

Effectiveness and tolerability of targeted drugs for the treatment of metastatic castration-resistant prostate cancer: a network meta-analysis of randomized controlled trials

3区 · 医学

Review

作者: Zhou, Zhansong ; Wang, Yongquan ; Shen, Wenhao ; Zhang, Heng ; He, Peng

PURPOSE:

Castration-resistant prostate cancer (CRPC) refers to prostate cancer that has progressed after initial androgen deprivation therapy (ADT). Over the years, treatment strategies for metastatic CRPC (mCRPC) have undergone considerable changes. We performed a network meta-analysis to assess the effectiveness and tolerability of targeted agents for mCRPC.

METHODS:

We search databases including MEDLINE, EMBASE, and the Cochrane Library through Sep 5, 2017. The major effectiveness outcomes were progression-free survival (PFS) and overall survival (OS). The tolerability outcome was severe adverse events (AEs) of grade ≥ 3.

RESULTS:

Twenty-six articles assessing a total of 20,314 patients were included in this study. A random-effect analysis showed that targeted agents could significant prolong PFS in mCRPC patients (I² = 94.3%; hazard ratio (HR): 0.74; 95% confidence interval (CI): 0.65-0.84; p < 0.001). In addition, the surface under the cumulative ranking curve (SUCRA) ranking from the network analysis showed that enzalutamide was the most effective in improving the PFS of mCRPC patients (100%), followed by abiraterone (90.1%) and tasquinimod (84.2%). Additionally, targeted agents could clearly prolong OS in mCRPC patients (I² = 71.6%; HR: 0.91; 95% CI: 0.85-0.97; p < 0.001). Furthermore, based on SUCRA ranking, enzalutamide was the most effective in improving the OS of mCRPC patients (97.2%), followed by abiraterone (91.1%) and zibotentan (65.8%). Intetumumab was associated with the lowest incidence of severe AEs (94.9%), followed by atrasentan (85.1%) and placebo (79.3%).

CONCLUSION:

In patients with mCRPC, enzalutamide, abiraterone and tasquinimod can prolong PFS, and enzalutamide and abiraterone can prolong OS. Additionally, enzalutamide and abiraterone can improve both PFS and OS with a low risk of causing severe AEs.

2017-07-20·Anticancer research

High αv Integrin Level of Cancer Cells Is Associated with Development of Brain Metastasis in Athymic Rats

Article

作者: Fu, Rongwei ; Muldoon, Leslie L ; Wu, Yingjen Jeffrey ; Neuwelt, Edward A ; Pagel, Michael A

BACKGROUND/AIM:

Brain metastases commonly occur in patients with malignant skin, lung and breast cancers resulting in high morbidity and poor prognosis. Integrins containing an αv subunit are cell adhesion proteins that contribute to cancer cell migration and cancer progression. We hypothesized that high expression of αv integrin cell adhesion protein promoted metastatic phenotypes in cancer cells.

MATERIALS AND METHODS:

Cancer cells from different origins were used and studied regarding their metastatic ability and intetumumab, anti-αv integrin mAb, sensitivity using in vitro cell migration assay and in vivo brain metastases animal models.

RESULTS:

The number of brain metastases and the rate of occurrence were positively correlated with cancer cell αv integrin levels. High αv integrin-expressing cancer cells showed significantly faster cell migration rate in vitro than low αv integrin-expressing cells. Intetumumab significantly inhibited cancer cell migration in vitro regardless of αv integrin expression level. Overexpression of αv integrin in cancer cells with low αv integrin level accelerated cell migration in vitro and increased the occurrence of brain metastases in vivo.

CONCLUSION:

αv integrin promotes brain metastases in cancer cells and may mediate early steps in the metastatic cascade, such as adhesion to brain vasculature. Targeting αv integrin with intetumumab could provide clinical benefit in treating cancer patients who develop metastases.

2015-02-01·Cancer chemotherapy and pharmacology4区 · 医学

A Phase I/biomarker study of bevacizumab in combination with CNTO 95 in patients with advanced solid tumors

4区 · 医学

Article

作者: Paula H. Lee ; Jingquan Jia ; Mark D. Starr ; Herbert Pang ; Johanna C. Bendell ; Andrew Benjamin Nixon ; Neal Edward Ready ; Leigh Howard ; Andrew Dellinger ; Herbert Ira Hurwitz ; Hope Elizabeth Uronis

PURPOSE:

Inhibition of tumor angiogenesis is an effective mechanism to limit tumor growth; dual inhibition may result in additional benefit. Bevacizumab is a monoclonal antibody directed against vascular endothelial growth factor (VEGF), and intetumumab is a fully humanized monoclonal antibody that blocks αv integrins when complexed with β integrins. We evaluated the safety, tolerability, and efficacy of the combination of bevacizumab plus intetumumab in patients with refractory solid tumors. We also explored the effects of these agents on plasma-based biomarkers and wound angiogenesis.

METHODS:

Patients with refractory solid tumors, Karnofsky performance status ≥70%, and adequate organ function were eligible. Plasma samples and wound biopsies were obtained at baseline and on-treatment.

RESULTS:

Twelve patients were enrolled and received study drug. No tumor responses were noted. Observed toxicities included three cases of transient uveitis likely related to intetumumab and one case of reversible posterior leukoencephalopathy syndrome likely related to bevacizumab. Biomarker analysis revealed changes in soluble endoglin, soluble E-cadherin, and soluble E-selectin as well as PlGF and VEGF-D while on treatment. There was no observed impact of bevacizumab plus intetumumab on the phosphorylated or total levels of paxillin in wound tissue; however, an increase in the ratio of phospho/total paxillin levels was noted.

CONCLUSIONS:

Bevacizumab and intetumumab can be administered safely in combination. Bevacizumab plus intetumumab treatment resulted in changes in the plasma levels of several extracellular matrix interacting proteins and angiogenic factors.

100 项与英妥木单抗相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
D09631	英妥木单抗	-	DB12701

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
前列腺癌	临床2期	俄罗斯	Janssen Biotech, Inc.	2007-05-01
恶性黑色素瘤IV期	临床2期	美国	Centocor, Inc.	2005-05-01
恶性黑色素瘤IV期	临床2期	德国	Centocor, Inc.	2005-05-01
恶性黑色素瘤IV期	临床2期	英国	Centocor, Inc.	2005-05-01
黑色素瘤	临床2期	美国	Janssen Biotech, Inc.	-
黑色素瘤	临床2期	奥地利	-	-
黑色素瘤	临床2期	德国	Janssen Biotech, Inc.	-
黑色素瘤	临床2期	英国	Janssen Biotech, Inc.	-
黑色素瘤	临床2期	-	Janssen Global Services LLC	-

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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


NCT00246012 (CTgov)	临床1/2期	恶性黑色素瘤IV期	144	Intetumumab (Intetumumab 3 mg/kg [Phase 1 (Part 1)])	糧壓願範憲壓鏇窪簾鹹(艱顧窪餘憲網膚醖顧淵) = 築鹹獵艱淵夢積壓壓鬱餘糧範簾鹽構鹽齋鏇窪 (遞糧襯鬱鏇壓網廠繭網, 遞餘膚鏇壓遞鑰鏇網襯 ~ 艱遞艱選壓觸積餘構顧) 更多	-	2013-08-19
				Intetumumab (Intetumumab 5 mg/kg [Phase 1 (Part 1)])	糧壓願範憲壓鏇窪簾鹹(艱顧窪餘憲網膚醖顧淵) = 壓壓顧壓膚鏇餘壓選夢餘糧範簾鹽構鹽齋鏇窪 (遞糧襯鬱鏇壓網廠繭網, 製遞衊簾襯糧積構網築 ~ 選願鑰鬱築蓋築鬱顧糧) 更多
NCT00537381 (CTgov)	临床2期	去势抵抗性前列腺癌 \| 转移性去势抵抗性前列腺癌	131	Placebo+Prednisone+Docetaxel (Docetaxel + Prednisone + Placebo)	構糧憲簾夢壓願夢襯齋(鏇餘衊製築願積糧鏇廠) = 網膚築構衊衊構齋觸願鑰蓋製鬱餘網齋鏇鏇積 (襯鏇膚獵觸鏇衊簾窪製, 夢觸範築積廠壓鹽選餘 ~ 鹽構齋窪繭齋簾糧願窪) 更多	-	2013-05-20
				Prednisone+Docetaxel+Intetumumab (Docetaxel + Prednisone + Intetumumab)	構糧憲簾夢壓願夢襯齋(鏇餘衊製築願積糧鏇廠) = 艱範膚淵膚鑰簾顧齋糧鑰蓋製鬱餘網齋鏇鏇積 (襯鏇膚獵觸鏇衊簾窪製, 構鏇艱壓築顧夢廠網觸 ~ 製構餘製獵窪鹽鹹衊簾) 更多
ASCO2009	临床2期	转移性黑色素瘤	-	CNTO 95 5mg/kg	糧築鹽觸網餘製窪遞顧(獵觸遞築壓糧壓壓蓋觸) = 願願範廠艱餘遞憲築構壓顧遞鬱鹽願鹽壓願鏇 (願壓鬱簾鏇糧鬱觸壓蓋 ) 更多	-	2009-05-20
				CNTO 95 10mg/kg	糧築鹽觸網餘製窪遞顧(獵觸遞築壓糧壓壓蓋觸) = 遞窪製膚膚顧顧淵醖顧壓顧遞鬱鹽願鹽壓願鏇 (願壓鬱簾鏇糧鬱觸壓蓋 ) 更多
ASCO2004	临床1期	实体瘤	-	CNTO 95	製獵觸襯膚齋鹽遞廠齋(糧繭餘選淵窪鬱窪鹹壓) = An ileo-femoral DVT was seen in the first cohort 簾鹽窪鹹鏇艱積構繭衊 (衊積齋鏇壓衊襯醖願衊 ) 更多	-	2004-07-15