This clinical trial evaluated the safety and tolerability of CRS-100, an investigational agent containing a live-attenuated strain of Listeria monocytogenes (Lm). CRS-100 is attenuated by genetic modification to limit cell to cell spread and invasion of liver cells. These attenuations result in decreased virulence of CRS-100 in mice but retain the ability of the investigational agent to stimulate immunity in test animals and generate anti-tumor activity in mice. The primary objective of this study was to determine the maximum tolerated dose (MTD) and to explore the safety profile of a single intravenous dose of CRS-100 in consenting volunteers. Immunological response to CRS-100 and tumor status of study participants were also measured. Participation in this first clinical trial with CRS-100 was restricted to adults with carcinoma refractory to standard treatment (or for whom no standard treatment is available) and who additionally had liver metastases.

开始日期2006-10-01

申办/合作机构

Anza Therapeutics, Inc.

100 项与 ANZ-100 相关的临床结果

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100 项与 ANZ-100 相关的转化医学

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100 项与 ANZ-100 相关的专利（医药）

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项与 ANZ-100 相关的文献（医药）

2012-02-01·Clinical Cancer Research1区 · 医学

A Live-Attenuated Listeria Vaccine (ANZ-100) and a Live-Attenuated Listeria Vaccine Expressing Mesothelin (CRS-207) for Advanced Cancers: Phase I Studies of Safety and Immune Induction

1区 · 医学

Article

作者: Moyer, Bentley ; Mathur, Shruti ; Nemunaitis, John ; Hampl, Johannes ; Murphy, Aimee Luck ; Hassan, Raffit ; Dubensky, Thomas W. ; Sugar, Elizabeth A. ; Eiden, Joseph E. ; Nir-Paz, Ran ; Jaffee, Elizabeth M. ; Giedlin, Martin ; Brockstedt, Dirk G. ; Illei, Peter ; Levine, Jordana ; Pons, Alice ; Sterman, Daniel H. ; Laheru, Daniel A. ; Cox, Andrea L. ; Le, Dung T. ; Louis, Jana-Lynn ; Lutz, Eric

AbstractPurpose: Listeria monocytogenes (Lm)-based vaccines stimulate both innate and adaptive immunity. ANZ-100 is a live-attenuated Lm strain (Lm ΔactA/ΔinlB). Uptake by phagocytes in the liver results in local inflammatory responses and activation and recruitment of natural killer (NK) and T cells, in association with increased survival of mice bearing hepatic metastases. The Lm ΔactA/ΔinlB strain, engineered to express human mesothelin (CRS-207), a tumor-associated antigen expressed by a variety of tumors, induces mesothelin-specific T-cell responses against mesothelin-expressing murine tumors. These two phase I studies test ANZ-100 and CRS-207 in subjects with liver metastases and mesothelin-expressing cancers, respectively.Experimental Design: A single intravenous injection of ANZ-100 was evaluated in a dose escalation study in subjects with liver metastases. Nine subjects received 1 × 106, 3 × 107, or 3 × 108 colony-forming units (cfu). CRS-207 was evaluated in a dose-escalation study in subjects with mesothelioma, lung, pancreatic, or ovarian cancers. Seventeen subjects received up to 4 doses of 1 × 108, 3 × 108, 1 × 109, or 1 × 1010 cfu.Results: A single infusion of ANZ-100 was well tolerated to the maximum planned dose. Adverse events included transient laboratory abnormalities and symptoms associated with cytokine release. Multiple infusions of CRS-207 were well tolerated up to 1 × 109 cfu, the determined maximum tolerated dose. Immune activation was observed for both ANZ-100 and CRS-207 as measured by serum cytokine/chemokine levels and NK cell activation. In the CRS-207 study, listeriolysin O and mesothelin-specific T-cell responses were detected and 37% of subjects lived ≥15 months.Conclusions: ANZ-100 and CRS-207 administration was safe and resulted in immune activation. Clin Cancer Res; 18(3); 858–68. ©2011 AACR.

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外链

KEGG	Wiki	ATC	Drug Bank
-	-	-	DB05967

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
恶性上皮肿瘤	临床1期	美国	Anza Therapeutics, Inc.	2006-10-01
肝转移	临床1期	美国	Anza Therapeutics, Inc.	2006-10-01
肝癌	临床1期	美国	Aduro BioTech, Inc.	-
肝癌	临床1期	-	Cerus Corp.	-

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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


Phase 1 Trial of CRS-100 (ASGCT2008)	临床1期	肝转移	6	CRS-100 1×10^6 cfu	蓋鬱餘憲選窪齋鏇網醖(膚鹹糧憲膚遞範網淵醖) = Transient fever and mild gastrointestinal symptoms were observed otherwise treatment was well tolerated 網遞壓鏇製網製糧齋網 (膚鬱襯壓簾築餘窪積壓 ) 更多	积极	2008-05-01
				CRS-100 1×10^7 cfu