AEG-35156(AEG-35156) - 药物靶点：XIAP_专利_临床

概要

基本信息

药物类型

ASO

别名

+ [3]

靶点

XIAP

作用机制

XIAP抑制剂(凋亡抑制蛋白-3抑制剂)

治疗领域

肿瘤免疫系统疾病消化系统疾病+ [6]

在研适应症-

非在研适应症

急性髓性白血病急性髓单核细胞白血病晚期乳腺癌+ [14]

原研机构

Idera Pharmaceuticals, Inc.

在研机构-

非在研机构

Aegera Therapeutics, Inc.

Idera, Inc.

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)无进展

特殊审评-

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结构/序列

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关联

11

项与 AEG-35156 相关的临床试验

NCT01018069

/ Terminated临床2期

An Open-Label Randomized Phase 2 Study of the X-Linked Inhibitor of Apoptosis (XIAP) Antisense AEG35156 Given in Combination With High-dose Cytarabine and Idarubicin in AML Following Failure of a Single Standard Dose Cytarabine Based Frontline Induction Regimen

To determine if AEG35156 can enhance the combined complete remission (CR) and CR with incomplete platelet recovery (CRp) rate of high-dose cytarabine and idarubicin in AML following failure of a single standard dose cytarabine based frontline induction regimen.

开始日期2009-11-01

申办/合作机构

Aegera Therapeutics, Inc.

NCT00882869

/ Completed临床1/2期

A Phase 1-2, Open-Label Study of The X-Linked Inhibitor of Apoptosis (XIAP) Antisense AEG35156 in Combination With Sorafenib in Patients With Advanced Hepatocellular Carcinoma (HCC)

AEG35156 is a second generation antisense which targets XIAP mRNA to lower XIAP levels and the apoptotic threshold of cancer cells, enhancing their sensitivity to intrinsic death and chemotherapy. Advanced HCC is an attractive target for AEG35156 since XIAP is highly expressed in HCC and may prevent cancer cells from undergoing apoptosis. Second generation antisense molecules are known to accumulate in liver where AEG35156 may down regulate XIAP protein expression in HCC cells thus promoting their apoptotic death.

开始日期2009-03-01

申办/合作机构

Aegera Therapeutics, Inc.

[+1]

NCT00768339

/ Terminated临床1/2期

AEG35156-204: A Phase 1-2, Multicenter, Open-Label Study of the X-Linked Inhibitor of Apoptosis (XIAP) Antisense AEG35156 in Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia and Indolent B-Cell Lymphomas

AEG35156 has shown early evidence of activity in patients with advanced indolent B-cell lymphomas in Phase 1 trials and merits further evaluation in this disease. This trial is designed to determine the recommended dose of AEG35156 in patients with relapsed or refractory chronic lymphocytic leukemia (CLL) and indolent B-cell lymphomas.

开始日期2008-09-01

申办/合作机构

Aegera Therapeutics, Inc.

[+1]

100 项与 AEG-35156 相关的临床结果

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100 项与 AEG-35156 相关的转化医学

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100 项与 AEG-35156 相关的专利（医药）

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19

项与 AEG-35156 相关的文献（医药）

2016-12-01·American Journal of Clinical Oncology

Randomized Phase II Study of the X-linked Inhibitor of Apoptosis (XIAP) Antisense AEG35156 in Combination With Sorafenib in Patients With Advanced Hepatocellular Carcinoma (HCC)

Article

作者: Jolivet, Jacques ; Lai, Maria ; Chong, Marc ; Tung, Steward ; Siu, Steven W. K. ; Kwok, Chloe ; Leung, Kwong Chuen ; Zee, Benny Chung-Ying ; Lee, Francis A. S. ; Kwong, Philip ; Lee, Conrad ; Chiang, Chi Leung ; Cheung, Foon Yiu

Objectives:This multicenter, randomized, open-label, phase II trial evaluated the efficacy and safety of AEG35156 in addition to sorafenib in patients with advanced hepatocellular carcinoma (HCC), as compared with sorafenib alone.Methods:Eligible patients were randomly assigned in a 2:1 ratio to receive AEG35156 (300 mg weekly intravenous infusion) in combination with sorafenib (400 mg twice daily orally) or sorafenib alone. The primary endpoint was progression-free survival (PFS). Other endpoints include overall survival (OS), objective response rates (ORR), and safety profile.Results:A total of 51 patients were enrolled; of them, 48 were evaluable. At a median follow-up of 16.2 months, the median PFS and OS were 4.0 months (95% CI, 1.2-4.1) and 6.5 months (95% CI, 3.9-11.5) for combination arm, and 2.6 (95% CI, 1.2-5.4) and 5.4 months (95% CI, 4.3-11.2) for sorafenib arm. Patients who had the study treatment interrupted or had dose modifications according to protocol did significantly better, in terms of PFS and OS, than those who had no dose reduction in combination arm and those in sorafenib arm. The ORR based on Choi and RECIST criteria were 16.1% and 9.7% in combination arm, respectively. The ORR was 0 in control arm. One drug-related serious adverse event of hypersensitivity occurred in the combination arm, whereas 2 gastrointestinal serious adverse events in the sorafenib arm.Conclusion:AEG35156 in combination with sorafenib showed additional activity in terms of ORR and was well tolerated. The benefit on PFS is moderate but more apparent in the dose-reduced subgroups.

2013-06-01·American Journal of Clinical Oncology4区 · 医学

Phase I Trial of AEG35156 an Antisense Oligonucleotide to XIAP Plus Gemcitabine in Patients With Metastatic Pancreatic Ductal Adenocarcinoma

4区 · 医学

Article

作者: Ramesh K. Ramanathan ; Diane Rensvold ; Sandy Kurtin ; Daniel D. Von Hoff ; Glen J. Weiss ; Jacques Jolivet ; Pavani Chalasani ; Chris Pretzinger ; Daruka Mahadevan

OBJECTIVESAEG35156 is an antisense oligonucleotide (ASO) that targets the X-linked inhibitor of apoptosis mRNA. Preclinical studies showed potent activity of AEG35156 in combination with gemcitabine in pancreatic ductal adenocarcinoma (PDA). A phase I study was conducted to establish the maximum-tolerated dose, safety, and antitumor activity of AEG35156 plus gemcitabine in metastatic PDA.METHODSFourteen patients with metastatic PDA were enrolled. Nine patients were treated at 350 mg IV and 5 patients at 500 mg IV of AEG35156, 3 weeks on/1 week off of a 28-day cycle. Gemcitabine was administered at 1000 mg/m(2) IV over 30 minutes immediately after AEG35156 in both groups. Because of perceived neurotoxicity dose deescalation to 350 mg was recommended.RESULTSAll 14 patients were evaluable for tolerability and toxicity. Toxicities include neutropenia (grade 3/4, 6 patients), thrombocytopenia (grade 3, 2 patients), peripheral neuropathy (grade 3, 2 patients), fatigue (grade 3, 4 patients), ascites (grade 3, 2 patients), and nausea/vomiting (grade 4, 2 patients). Five patients (45%) experienced stable disease with a median progression-free survival of 58 days (95% CI, 52-107 d).CONCLUSIONSThe maximum-tolerated dose is AEG35156 500 mg plus gemcitabine 1000 mg/m(2) given on days 1, 8, and 15 every 28 days. AEG35156 plus gemcitabine failed to show significant clinical activity in advanced PDA.

2013-05-01·Cancer Letters1区 · 医学

Pulling the plug on a cancer cell by eliminating XIAP with AEG35156

1区 · 医学

Review

作者: LaCasse, Eric C

XIAP, the X-linked inhibitor of apoptosis, is the best example of an endogenous cellular suppressor of apoptosis. XIAP is effective because it directly limits the activity of several critical death-inducing caspases, notably caspase-3, -7 and -9, either by direct enzyme inhibition or through ubiquitin-mediated proteasomal degradation. Furthermore, XIAP acts simultaneously at several nodes in the apoptotic cascade, blocking both the intrinsic and extrinsic death pathways, and thereby preventing feed-forward amplification loops that would otherwise lead to cell death. XIAP over-expression, or increased activity, is associated with cancer progression, resistance to therapy and poor prognosis. Targeting XIAP gene expression by antisense oligonucleotides, or other approaches, demonstrates anti-cancer effects with XIAP down-regulation. These early preclinical studies led to the development of a clinical candidate mixed-backbone antisense oligonucleotide, AEG35156, against XIAP for the treatment of cancer. Published clinical results for the first-in-class and first-in-human trials of AEG35156 are summarized herein, including single agent and combination chemotherapy phase-I or -II trials for solid tumors, lymphoma, and acute myeloid leukemia. These trials demonstrate the safety of AEG35156, as well as some initial promising signs of anti-cancer activity.

100 项与 AEG-35156 相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
-	-	-	DB06184

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
晚期非小细胞肺癌	临床2期	美国	Aegera Therapeutics, Inc.	2007-09-01
急性髓单核细胞白血病	临床2期	美国	Aegera Therapeutics, Inc.	2005-10-01
难治性急性髓细胞白血病	临床2期	加拿大	Aegera Therapeutics, Inc.	2005-10-01
难治性急性髓细胞白血病	临床2期	美国	Aegera Therapeutics, Inc.	2005-10-01
急性髓性白血病	临床2期	-	Idera, Inc.	-
肝细胞癌	临床2期	-	Idera, Inc.	-
肝细胞癌	临床2期	-	Idera, Inc.	-
胰腺癌	临床2期	-	Idera, Inc.	-
胰腺癌	临床2期	-	Idera, Inc.	-
急性髓单核细胞白血病	药物发现	加拿大	Aegera Therapeutics, Inc.	2005-10-01

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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


NCT00882869 (Pubmed) 人工标引	临床2期	晚期肝细胞癌	51	AEG35156+Sorafenib	(夢構襯鹽壓蓋獵憲壓鬱) = 遞憲餘餘鬱夢蓋襯繭獵襯鹹範醖網糧壓鏇夢鏇 (淵鏇艱獵顧積襯憲憲鹹, 1.2 ~ 4.1) 更多	积极	2016-12-01
NCT00882869 (Pubmed) 人工标引	临床2期	晚期肝细胞癌	51	Sorafenib	(夢構襯鹽壓蓋獵憲壓鬱) = 簾醖遞積衊鹽衊醖齋襯襯鹹範醖網糧壓鏇夢鏇 (淵鏇艱獵顧積襯憲憲鹹, 1.2 ~ 5.4) 更多	积极	2016-12-01
ASCO2008	临床1期	肿瘤	-	AEG35156	糧鹽遞廠醖醖襯選鑰淵(觸範範鏇鏇淵鏇窪鏇鏇) = Three DLTs were observed at AEG35156 350mg: Grade 3 chills/lethargy (mesothelioma), grade 3 transaminitis (colon), transient grade 3 chills/tumour lysis syndrome/transaminitis (small lymphocytic lymphoma) 壓鏇鹹構遞夢範築簾夢 (醖醖廠餘蓋選衊餘憲簾 ) 更多	-	2008-05-20
ASCO2006	临床1期	肿瘤	16	AEG35156	(壓鏇蓋構衊製觸壓艱鏇) = 夢醖繭觸夢遞廠鹹艱艱構糧鹽蓋製蓋鹽顧鬱襯 (鬱憲鹹淵醖廠繭鹹齋齋 )	-	2006-06-20