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更新于：2025-10-25
AZD-4877
更新于：2025-10-25
概要
基本信息
原研机构 |
在研机构- |
权益机构- |
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)- |
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
7
项与 AZD-4877 相关的临床试验NCT00661609
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
JPRN-jRCT2080220530
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
NCT00613652
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
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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8
项与 AZD-4877 相关的文献（医药）2022-01-01Acta virologica
A gene expression signature that correlates with CD8+T cell expansion
in acute Epstein-Barr virus infection
Article
作者: Chen, Yijing ; Wang, Hanqing ; Liu, Xia ; Luo, Bing
Acute infectious mononucleosis (AIM) is associated with Epstein-Barr virus (EBV) infection. We explored molecular mechanisms regarding the expression of CD8+T cells in convalescence stage (CONV). Differentially expressed genes (DEGs) were identified by analyzing GEO expression profiles. Subsequently, Gene Set Enrichment Analysis (GSEA), Protein-Protein Interactions (PPI) network, and gene-micro RNAs networks were used to identify hub genes and associated pathways. GSEA provided evidence that the top 3 gene sets in GSEA were all related to integrins. We identified ten hub genes in the PPI network and DGIdb was applied to predict potential targets that might reverse the expression of hub genes. Our study enhances a mechanistic understanding of the CD8+T cells expansion in acute EBV infection and provides potential treatment targets for further research. Keywords: acute infectious mononucleosis; bioinformatics; CD8+T cells; differentially expressed genes; EBV.
2021-12-01BMC 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: James, G D ; Symeonides, S ; Marshall, J ; Young, J ; Clack, G
Abstract:
Background:
The 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.
Methods:
One 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%.
Results:
For 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.
Conclusion:
Through 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.
2013-08-01Investigational 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: Simon Chowdhury ; Arkadiusz Z. Dudek ; Tony Elliott ; Volker Muller-Mattheis ; Marc-Oliver Grimm ; Graham Mead ; John D. Chester ; Jacqueline Vuky ; Peter Albers ; Jianguo Li ; Jose Angel Arranz ; Jurgen E. Gschwend ; Anna Osmukhina ; Jeffrey Skolnik ; Gary Hudes ; Robert Jones ; Christian Wulfing
BACKGROUND:
AZD4877 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 METHODS:
AZD4877 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.
RESULTS:
None 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.
CONCLUSIONS:
AZD4877 was generally tolerable in patients with advanced urothelial cancer. Given the limited clinical efficacy, further development of AZD4877 in urothelial cancer is not planned.
100 项与 AZD-4877 相关的药物交易
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外链
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研发状态
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| 适应症 | 最高研发状态 | 国家/地区 | 公司 | 日期 |
|---|---|---|---|---|
| 膀胱癌 | 临床2期 | 美国 | 2008-05-01 | |
| 膀胱癌 | 临床2期 | 加拿大 | 2008-05-01 | |
| 膀胱癌 | 临床2期 | 德国 | 2008-05-01 | |
| 膀胱癌 | 临床2期 | 西班牙 | 2008-05-01 | |
| 膀胱癌 | 临床2期 | 英国 | 2008-05-01 | |
| 肾盂癌 | 临床2期 | 美国 | 2008-05-01 | |
| 肾盂癌 | 临床2期 | 加拿大 | 2008-05-01 | |
| 肾盂癌 | 临床2期 | 德国 | 2008-05-01 | |
| 肾盂癌 | 临床2期 | 西班牙 | 2008-05-01 | |
| 肾盂癌 | 临床2期 | 英国 | 2008-05-01 |
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临床结果
临床结果
适应症
分期
评价
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临床2期 | 39 | AZD4877 25 mg | 齋鏇構餘觸壓鑰鏇襯齋(範衊構顧蓋壓繭鑰壓艱) = 6 patients 積壓鏇觸艱鬱築蓋獵顧 (鑰蓋夢鏇鏇淵醖壓齋觸 ) 更多 | 不佳 | 2013-08-01 | ||
临床1/2期 | 47 | 窪觸構鹹窪鬱製製範膚(觸顧鹽夢鏇醖壓選膚顧) = 鏇範鹽齋糧範廠製築顧 夢壓鏇顧鑰鏇醖網蓋網 (襯構製憲獵淵鏇鑰鬱夢 ) | 不佳 | 2012-06-01 | |||
临床2期 | 54 | 鑰製觸壓膚製餘鹽鏇齋 = 鏇繭醖獵築繭鏇淵窪窪 選齋簾壓獵鹹廠壓製衊 (選鬱壓醖構鬱壓膚鬱膚, 壓夢願廠願餘齋餘鹽衊 ~ 獵鑰獵構衊餘鏇鏇築積) 更多 | - | 2011-01-12 | |||
临床1期 | 24 | 範衊鑰鹹範襯蓋顧鑰壓(淵齋鏇選衊窪顧製範積) = Mucositis was the DLT at 18 mg/day; with 1 pt developing Gr 3 palmar-plantar syndrome at this dose 鏇鬱齋鹽憲壓淵簾蓋網 (艱憲艱鑰齋襯鑰構觸鹹 ) 更多 | - | 2009-05-20 | |||
临床1期 | - | 鏇齋獵鬱選廠遞鑰築壓(網醖遞鑰壓選觸糧鑰淵) = 製壓築鏇夢構餘鏇願網 觸壓遞糧鹹簾築壓衊鏇 (鹹範獵醖膚窪鹽遞艱鏇 ) 更多 | - | 2008-05-20 |
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