Tovetumab(Tovetumab) - 药物靶点：PDGFRα_专利_临床

概要

基本信息

药物类型

单克隆抗体

别名

Anti-PDGFRa MAb、Tovetumab (USAN)

靶点

PDGFRα

作用机制

PDGFRα调节剂(血小板衍生生长因子受体α调节剂)

治疗领域

肿瘤神经系统疾病呼吸系统疾病+ [1]

在研适应症-

非在研适应症

晚期非小细胞肺癌晚期恶性实体瘤胶质母细胞瘤+ [3]

原研机构

Cambridge Antibody Technology

在研机构-

非在研机构

MedImmune LLCCambridge Antibody Technology

AstraZeneca PLC

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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序列信息

Sequence Code 319372699L

来源: *****

Sequence Code 319372631H

来源: *****

关联

5

项与 Tovetumab 相关的临床试验

NCT01268566 / Completed临床2期

A Phase 2 Study of MEDI-575 in Adult Subjects With Recurrent Glioblastoma Multiforme

The primary objective of this Phase II study is to evaluate the progression-free survival at 6 months in adult subjects with a first recurrence of Glioblastoma Multiforme who are treated with MEDI-575.

开始日期2011-01-01

申办/合作机构

MedImmune LLC

NCT01268059 / Terminated临床1/2期

A Phase 1b/2 Randomized Study of MEDI-575 in Combination With Carboplatin Plus Paclitaxel Versus Carboplatin Plus Paclitaxel Alone in Adult Subjects With Previously Untreated, Advanced Non-Small Cell Lung Cancer

The purpose of this study is to evaluate the dose, antitumor activity, safety and pharmacology of MEDI-575 in combination with carboplatin/paclitaxel in subjects with previously untreated, advanced non-small cell lung cancer (NSCLC).

开始日期2010-12-16

申办/合作机构

MedImmune LLC

JPRN-jRCT2080221095 / Unknown status临床1期

A Phase I, Open-Label Study to Assess the Safety, Tolerability and Pharmacokinetics of Ascending Doses of MEDI-575 in Patients With Advanced Solid Malignancies

开始日期2010-05-12

申办/合作机构

AstraZeneca PLC

[+1]

100 项与 Tovetumab 相关的临床结果

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100 项与 Tovetumab 相关的转化医学

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100 项与 Tovetumab 相关的专利（医药）

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11

项与 Tovetumab 相关的文献（医药）

2021-02-01·ESMO Open3区 · 医学

Expression and prognostic significance of PDGF ligands and receptors across soft tissue sarcomas

3区 · 医学

ArticleOA

作者: Toulmonde, M ; Chibon, F ; Italiano, A ; Brahmi, M ; Karanian, M ; Bonvalot, S ; Lesluyes, T ; Le Loarer, F ; Blay, J-Y ; Valentin, T ; Le Guellec, S ; Le Cesne, A ; Mir, O ; Chevreau, C ; Coindre, J-M ; Dufresne, A ; Penel, N

BACKGROUNDWhile the anti-PDGFRA antibody olaratumab failed to confirm an impact on survival in unselected advanced soft tissue sarcoma (STS) patients, the level of expression and the prognosis of platelet-derived growth factor (PDGF) receptors and ligands in STS remain unclear.PATIENTS AND METHODSWe analyzed PDGF ligands and receptors' expression levels in a series of 255 patients with different histologies of STS [gastrointestinal stromal tumor (GIST), myxoid liposarcoma (MLPS), sarcoma with complex genomics, synovial sarcoma (SyS)] with Agilent single-color micro-arrays. We explored expression levels as prognostic values in univariate and multivariate analysis using R software (version 3.4.2).RESULTSComplex patterns of correlation of expression between ligands and receptors were observed for each histotype. PDGFA levels were highest in SyS and lowest in MLPS (P < 4 × 10^-9), PDGFB and C levels were lower in GIST (P < 2 × 10^-15 and P < 3 × 10^-9) while PDGFD expression was similar across histological subtypes. PDGF receptor (PDGFR) A expression was lowest in MLPS (P < 0.002), whereas PDGFRB and L expressions were lowest in GIST and SyS (P < 0.0004). Interestingly, high PDGFA expression levels were associated with higher risk of metastasis (P = 0.006), whereas PDGFD levels above average were associated with a reduced risk of metastasis (P = 0.01) in univariate and multivariate analysis.CONCLUSIONSThe expression of PDGF ligands and receptors varies across sarcoma histological subtypes. PDGFA and D expression levels independently and inversely correlate with the risk of metastatic relapse.

2021-01-01·The AAPS Journal3区 · 医学

A Novel Pharmacodynamic Biomarker and Mechanistic Modeling Facilitate the Development of Tovetumab, a Monoclonal Antibody Directed Against Platelet-Derived Growth Factor Receptor Alpha, for Cancer Therapy

3区 · 医学

Article

作者: Wang, Bing ; Vainshtein, Inna ; Schneider, Amy ; Liang, Meina ; Roskos, Lorin

Tovetumab (MEDI-575) is a fully human IgG2κ monoclonal antibody that specifically binds to human platelet-derived growth factor receptor alpha (PDGFRα) and blocks receptor signal transduction by PDGF ligands. The affinity of tovetumab determined using surface plasmon resonance technology and flow cytometry demonstrated comparable binding affinity for human and monkey PDGFRα. In single and repeat-dose monkey pharmacokinetic-pharmacodynamic (PK-PD) studies, tovetumab administration resulted in dose-dependent elevation of circulating levels of PDGF-AA, a member of the PDGF ligand family, due to displacement of PDGF-AA from PDGFRα by tovetumab and subsequent blockade of PDGFRα-mediated PDGF-AA degradation. As such, PDGF-AA accumulation is an indirect measurement of receptor occupancy and is a novel PD biomarker for tovetumab. The nonlinear PK of tovetumab and dose-dependent increase in circulating PDGF-AA profiles were well described by a novel mechanistic model, in which tovetumab and PDGF-AA compete for the binding to PDGFRα. To facilitate translational simulation, the internalization half-lives of PDGF-AA and tovetumab upon binding to PDGFRα were determined using confocal imaging to be 14 ± 4 min and 30 ± 8 min, respectively. By incorporating PDGFRα internalization kinetics, the model not only predicted the target receptor occupancy by tovetumab, but also the biologically active agonistic ligand-receptor complex. This work described a novel PD biomarker approach applicable for anti-receptor therapeutics and the first mechanistic model to delineate the in vivo tri-molecular system of a drug, its target receptor, and a competing endogenous ligand, which collectively have been used for optimal dose recommendation supporting clinical development of tovetumab.

2019-05-01·Clinical Lung Cancer2区 · 医学

Phase 1b/2 Randomized Study of MEDI-575 in Combination With Carboplatin Plus Paclitaxel Versus Carboplatin Plus Paclitaxel Alone in Adult Patients With Previously Untreated Advanced Non–Small-Cell Lung Cancer

2区 · 医学

Article

作者: Blumenschein, George R ; Gadgeel, Shirish ; Takahashi, Toshiaki ; Dar, Mohammed ; Li, Xia ; Wheatley-Price, Paul

INTRODUCTIONPlatinum doublet chemotherapy has represented the standard of care in advanced non-small-cell lung cancer for decades. Targeting platelet-derived growth factor receptors (PDGFR) is a potential mechanism to improve the efficacy of first-line therapy. This randomized phase 1b/2 trial investigated the addition of the anti-PDGFRα monoclonal antibody MEDI-575 to first-line carboplatin/paclitaxel (CP) chemotherapy.PATIENTS AND METHODSThe phase 1b component was a dose-escalation study combining MEDI-575 with carboplatin area under the plasma concentration versus time curve 6 and paclitaxel 200 mg/m² (CPM), with the end point of identifying a recommended phase 2 dose. The phase 2 component randomized patients to CPM or CP, with primary end point of progression-free survival. Secondary end points included overall survival, overall response rate, and adverse event rates.RESULTSOverall, 99 patients were enrolled and received either CPM (n = 53; 4 phase 1b, 49 phase 2) or CP (n = 46). Demographics were as follows: 63/36 male/female, 78/21 aged ≤ 70/> 70 years; 37/62 squamous/nonsquamous, 42/53 Eastern Cooperative Oncology Group performance status 0/1. The phase 2 portion of the trial did not meet its primary end point: progression-free survival was shorter with CPM (4.6 vs. 5.5 months) than CP. No significant difference was seen in overall response rate (31.7% vs. 22.5%) or median overall survival (10.0 vs. 11.8 months). More serious adverse events were observed in patients receiving CPM (47% vs. 40%); in particular, 9 patients in the CPM group had significant gastrointestinal or respiratory adverse events (including abscess, perforation, and pneumothorax).CONCLUSIONThe addition of MEDI-575 to CP chemotherapy as first-line treatment of advanced non-small-cell lung cancer did not improve efficacy and resulted in increased toxicity.

100 项与 Tovetumab 相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
D10411	Tovetumab	-	DB12609

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
复发性胶质母细胞瘤	临床2期	美国	MedImmune LLC	2011-01-01
晚期非小细胞肺癌	临床2期	匈牙利	MedImmune LLC	2010-12-16
晚期非小细胞肺癌	临床2期	加拿大	MedImmune LLC	2010-12-16
晚期非小细胞肺癌	临床2期	波兰	MedImmune LLC	2010-12-16
晚期非小细胞肺癌	临床2期	德国	MedImmune LLC	2010-12-16
晚期非小细胞肺癌	临床2期	美国	MedImmune LLC	2010-12-16
晚期非小细胞肺癌	临床2期	法国	MedImmune LLC	2010-12-16
晚期非小细胞肺癌	临床2期	日本	MedImmune LLC	2010-12-16
胶质母细胞瘤	临床2期	-	Cambridge Antibody Technology	-
非小细胞肺癌	临床2期	-	Cambridge Antibody Technology	-

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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


NCT01268059 (CTgov)	临床1/2期	晚期非小细胞肺癌	99	Carboplatin+MEDI-575+Paclitaxel (Carboplatin/Paclitaxel + MEDI-575 - Phase 1b)	築構廠齋願醖積鬱鹹願(網獵蓋醖顧鏇膚鹽簾顧) = 築鹽網積鏇積蓋淵鏇夢淵顧構積築遞鑰願夢網 (膚繭鏇壓積膚餘鬱鏇憲, 構餘艱觸簾衊壓願艱顧 ~ 顧蓋繭願觸齋艱網艱鏇) 更多	-	2020-12-23
NCT01268059 (CTgov)	临床1/2期	晚期非小细胞肺癌	99	Carboplatin+Paclitaxel (Carboplatin/Paclitaxel - North America/European Union (EU))	齋鑰範憲鏇簾選醖簾襯(網簾蓋網繭壓艱觸膚鹽) = 糧顧遞築選遞範淵廠遞繭糧夢顧鑰製築醖衊繭 (範願夢醖簾簾餘艱鹽選, 製齋製顧醖繭糧襯積窪 ~ 選鹹遞繭淵願壓築襯餘) 更多	-	2020-12-23
NCT01268059 (Pubmed) 人工标引	临床1/2期	非小细胞肺癌一线	95	Carboplatin+Paclitaxel+MEDI-575	(窪壓鹽顧範壓鏇窪網積) = 簾選鬱醖鑰構鬱壓鏇艱製壓淵鏇觸獵鹽鑰網構 (廠鬱遞選夢獵繭鑰衊製 ) 更多	不佳	2019-05-01
NCT01268059 (Pubmed) 人工标引	临床1/2期	非小细胞肺癌一线	95	Carboplatin+Paclitaxel	(窪壓鹽顧範壓鏇窪網積) = 淵製構築壓壓憲鹽齋蓋製壓淵鏇觸獵鹽鑰網構 (廠鬱遞選夢獵繭鑰衊製 ) 更多	不佳	2019-05-01
NCT01268566 (CTgov)	临床2期	多形性胶质母细胞瘤 \| 复发性胶质母细胞瘤	62	MEDI-575	遞壓夢憲鬱廠觸鏇選範(襯蓋積築襯鹽糧鹹襯積) = 鏇艱蓋艱觸鏇艱廠構壓製獵夢鏇襯選衊憲鹹壓 (齋廠繭範糧簾積壓蓋築, 築膚襯構選艱選鏇淵壓 ~ 夢遞鬱積範願獵蓋觸積) 更多	-	2017-04-06
NCT01268566 (Pubmed \| J Neurooncol) 人工标引	临床2期	复发性胶质母细胞瘤	56	MEDI-575	(鹽鏇選鑰顧鏇襯憲顧蓋) = 觸繭鹹齋憲淵網製構獵餘繭繭蓋醖齋繭觸艱鏇 (鬱夢簾糧襯鏇壓餘襯鏇, 8.1 ~ 24.9) 更多	不佳	2017-01-01