AZD-4877(AZD-4877) - 药物靶点：KIF11_在研适应症：实体瘤_专利_临床

概要

基本信息

药物类型

小分子化药

别名

靶点

KIF11

作用机制

KIF11抑制剂(驱动蛋白-1抑制剂)

治疗领域

肿瘤

在研适应症

实体瘤

非在研适应症

急性早幼粒细胞白血病晚期恶性实体瘤膀胱癌+ [8]

原研机构

阿斯利康制药有限公司

在研机构

University of Colorado Health Sciences CenterAstraZeneca, Inc.

Sarah Cannon Research Institute LLC

非在研机构

AstraZeneca PLC

最高研发阶段临床1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

分子式C28H33N5O2S

InChIKeySMFXSYMLJDHGIE-UHFFFAOYSA-N

CAS号758722-49-5

关联

8

项与 AZD-4877 相关的临床试验

EUCTR2008-000907-27-DE

/ Not yet recruitingN/A

A Phase II, Single Arm, Single Agent, Multicentre, Adaptive 2-Stage Study to Evaluate the Efficacy, Safety and Pharmacokinetics of AZD4877 Administered Weekly in Patients with Recurrent Advanced Urothelial Cancer

开始日期2008-06-06

申办/合作机构

AstraZeneca AB

NCT00661609

/ Completed临床2期

A Phase II, Single Arm, Single Agent, Multicentre, Adaptive 2-Stage Study to Evaluate the Efficacy, Safety, and Pharmacokinetics of AZD4877 Administered Weekly in Patients With Recurrent Advanced Urothelial Cancer

The purpose of this Phase II study is to determine if AZD4877, an experimental drug that is a novel anti-mitotic agent (Eg5 or Kinesin Spindle Protein inhibitor that interferes with tumor cell division leading to tumor growth), can reduce tumor sizes in patients with bladder cancer

开始日期2008-05-01

申办/合作机构

AstraZeneca PLC

JPRN-jRCT2080220530

/ Unknown status临床1期

A Phase I, Open-Label, Dose-Escalation Study to Assess the Safety, Tolerability and Pharmacokinetics of AZD4877 Administered Weekly in Japanese Adult Patients With Advanced Solid Malignancies

开始日期2008-03-18

申办/合作机构

AstraZeneca PLC

100 项与 AZD-4877 相关的临床结果

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100 项与 AZD-4877 相关的转化医学

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100 项与 AZD-4877 相关的专利（医药）

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7

项与 AZD-4877 相关的文献（医药）

2021-12-01·BMC Cancer2区 · 医学

Assessment of various continual reassessment method models for dose-escalation phase 1 oncology clinical trials: using real clinical data and simulation studies

2区 · 医学

ArticleOA

作者: Young, J ; Clack, G ; Symeonides, S ; James, G D ; Marshall, J

AbstractBackgroundThe continual reassessment method (CRM) identifies the maximum tolerated dose (MTD) more efficiently and identifies the true MTD more frequently compared to standard methods such as the 3 + 3 method. An initial estimate of the dose-toxicity relationship (prior skeleton) is required, and there is limited guidance on how to select this. Previously, we compared the CRM with six different skeletons to the 3 + 3 method by conducting post-hoc analysis on a phase 1 oncology study (AZD3514), each CRM model reduced the number of patients allocated to suboptimal and toxic doses. This manuscript extends this work by assessing the ability of the 3 + 3 method and the CRM with different skeletons in determining the true MTD of various “true” dose-toxicity relationships.MethodsOne thousand studies were simulated for each “true” dose toxicity relationship considered, four were based on clinical trial data (AZD3514, AZD1208, AZD1480, AZD4877), and four were theoretical. The 3 + 3 method and 2-stage extended CRM with six skeletons were applied to identify the MTD, where the true MTD was considered as the largest dose where the probability of experiencing a dose limiting toxicity (DLT) is ≤33%.ResultsFor every true dose-toxicity relationship, the CRM selected the MTD that matched the true MTD in a higher proportion of studies compared to the 3 + 3 method. The CRM overestimated the MTD in a higher proportion of simulations compared to the 3 + 3 method.The proportion of studies where the correct MTD was selected varied considerably between skeletons. For some true dose-toxicity relationships, some skeletons identified the true MTD in a higher proportion of scenarios compared to the skeleton that matched the true dose-toxicity relationship.ConclusionThrough simulation, the CRM generally outperformed the 3 + 3 method for the clinical and theoretical true dose-toxicity relationships. It was observed that accurate estimates of the true skeleton do not always outperform a generic skeleton, therefore the application of wide confidence intervals may enable a generic skeleton to be used. Further work is needed to determine the optimum skeleton.

2013-08-01·Investigational New Drugs3区 · 医学

Phase II study to assess the efficacy, safety and tolerability of the mitotic spindle kinesin inhibitor AZD4877 in patients with recurrent advanced urothelial cancer

3区 · 医学

Article

作者: Jacqueline Vuky ; Arkadiusz Z. Dudek ; John D. Chester ; Simon Chowdhury ; Marc-Oliver Grimm ; Robert Jones ; Anna Osmukhina ; Tony Elliott ; Graham Mead ; Gary Hudes ; Volker Muller-Mattheis ; Jeffrey Skolnik ; Christian Wulfing ; Jurgen E. Gschwend ; Jose Angel Arranz ; Jianguo Li ; Peter Albers

BACKGROUNDAZD4877 is a potent inhibitor of the mitotic spindle kinesin, Eg5. Early-phase clinical studies in a broad range of cancers showed that AZD4877 is well tolerated. This Phase II study evaluated the efficacy, safety and pharmacokinetics (Cmax) of AZD4877 in patients with previously treated advanced urothelial cancer (ClinicalTrials.gov identifier NCT00661609).PATIENTS AND METHODSAZD4877 25 mg was administered once-weekly for 3 weeks of each 4-week cycle until disease progression, death, unacceptable toxicity or withdrawal. The primary objective was to determine the objective response rate (RECIST). Recruitment was to be halted if ≤ 2 of the first 20 evaluable patients achieved an objective tumor response. Cmax was assessed on days 1 and 8 of cycle 1.RESULTSNone of the first 20 patients evaluable for efficacy achieved an objective response; enrollment was therefore halted. During this initial analysis, a further 21 patients were recruited. Overall, 39 patients were evaluable for efficacy, including one with confirmed partial response (PR) and seven patients with stable disease for ≥ 8 weeks (including one unconfirmed PR). The most commonly reported treatment-related adverse events (TRAEs) were neutropenia (22 patients), fatigue (12), leukopenia (7) and constipation (6); the most commonly reported grade ≥ 3 TRAE was neutropenia (21). Four patients had serious TRAEs. On days 1 and 8, the geometric mean Cmax of AZD4877 was 138 ng/ml (CV = 75 %) and 144 ng/ml (CV = 109 %), respectively.CONCLUSIONSAZD4877 was generally tolerable in patients with advanced urothelial cancer. Given the limited clinical efficacy, further development of AZD4877 in urothelial cancer is not planned.

2013-04-01·Investigational New Drugs3区 · 医学

A Phase I trial of the kinesin spindle protein (Eg5) inhibitor AZD4877 in patients with solid and lymphoid malignancies

3区 · 医学

Article

作者: Dennis Huszar ; Joe J. Stephenson ; Anna Osmukhina ; Jianguo Li ; Jeffrey M. Skolnik ; Gary K. Schwartz ; John F. Gerecitano ; Kaida Wu ; Nancy L. Lewis ; Zhiping You

BACKGROUNDThis Phase I study assessed the safety and maximum tolerated dose (MTD) of the kinesin spindle protein inhibitor AZD4877 in patients with relapsed/refractory solid tumors and lymphoma.METHODSIn this multicenter study, a standard 3 + 3 dose-escalation design was used. AZD4877 was given as an intravenous infusion on days 1, 4, 8 and 11 of each 21-day cycle. Responses were assessed with CT scans +/- PET after 6 and 12 weeks, then every 12 weeks while on therapy. An additional four patients with lymphoma were enrolled at the MTD.RESULTS29 patients were enrolled and 22 patients received at least one dose of AZD4877 and were evaluable for safety. The MTD was 11 mg. Dose-limiting toxicity was neutropenia (n = 2 patients, 15 mg cohort). The most common adverse events were grade 1/2 fatigue, nausea, neutropenia and dyspnea. AZD4877 exposure generally increased with dose, with mean elimination half-life approximately 16 h at the MTD. Pharmacodynamic analyses demonstrated moderate correlation between plasma drug concentrations at 6 or 24 h and monoaster formation in peripheral blood mononuclear cells (PBMCs).CONCLUSIONSAZD4877 is generally well-tolerated with pharmacodynamic evidence of target inhibition in circulating PBMCs.

100 项与 AZD-4877 相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
-	-	-	DB11671

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
尿道肿瘤	药物发现	加拿大	AstraZeneca PLC	2008-05-01
尿道肿瘤	药物发现	德国	AstraZeneca PLC	2008-05-01
尿道肿瘤	药物发现	西班牙	AstraZeneca PLC	2008-05-01
尿道肿瘤	药物发现	英国	AstraZeneca PLC	2008-05-01
尿道肿瘤	药物发现	美国	AstraZeneca PLC	2008-05-01
膀胱尿路上皮癌	药物发现	英国	AstraZeneca PLC	2008-05-01
膀胱尿路上皮癌	药物发现	德国	AstraZeneca PLC	2008-05-01
膀胱尿路上皮癌	药物发现	美国	AstraZeneca PLC	2008-05-01
膀胱尿路上皮癌	药物发现	西班牙	AstraZeneca PLC	2008-05-01
膀胱尿路上皮癌	药物发现	加拿大	AstraZeneca PLC	2008-05-01

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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


NCT00486265 (Pubmed \| Invest New Drugs)	临床1/2期	难治性急性髓细胞白血病	47	AZD4877	(遞網獵鹽鏇淵鏇簾淵範) = 齋構遞憲淵壓憲餘窪築襯願製壓衊夢餘構廠膚 (構襯鏇繭簾顧鹽築艱窪 )	不佳	2012-06-01
NCT00661609 (CTgov)	临床2期	输尿管肿瘤 \| 肾盂癌 \| 膀胱尿路上皮癌 \| 复发性尿路上皮癌 \| 膀胱癌 \| 尿道肿瘤	54	AZD4877	蓋壓鬱憲網艱繭膚繭鑰(顧齋廠積獵窪淵餘構壓) = 製襯積鹹衊鹹鹽襯鬱糧選選觸淵鬱鏇壓鑰壓膚 (顧鏇憲窪鹹襯積鏇餘網, 窪簾廠鏇顧積築簾蓋餘 ~ 蓋簾觸構選窪廠膚鬱遞) 更多	-	2011-01-12
ASCO2009	临床1期	难治性急性髓细胞白血病巩固	24	AZD4877	(鬱構築遞鹹衊構願觸鹽) = Mucositis was the DLT at 18 mg/day; with 1 pt developing Gr 3 palmar-plantar syndrome at this dose 選鬱構鏇夢獵繭願觸積 (廠簾簾築鹹構積鑰築衊 ) 更多	-	2009-05-20
ASCO2008	临床1期	晚期恶性实体瘤	-	AZD4877	(選觸壓艱鑰鏇衊觸壓製) = 衊遞壓鑰壓壓鹽築餘築範顧選廠獵選觸遞觸壓 (衊製獵顧糧繭製顧壓構 ) 更多	-	2008-05-20