(Xentuzumab) - 药物靶点：IGF-1 x IGF-2_在研适应症：乳腺癌，HR阳性/HER2阴性乳腺癌，转移性乳腺癌_专利_临床

概要

基本信息

药物类型

双特异性抗体

别名

靶点

IGF-1 x IGF-2

作用机制

IGF-1抑制剂(胰岛素样生长因子-I抑制剂)、IGF-2抑制剂(胰岛素样生长因子Ⅱ抑制剂)

治疗领域

肿瘤呼吸系统疾病皮肤和肌肉骨骼疾病+ [1]

在研适应症

乳腺癌HR阳性/HER2阴性乳腺癌转移性乳腺癌+ [5]

非在研适应症

ER阳性乳腺癌局部晚期乳腺癌

原研机构

C.H. Boehringer Sohn AG & Co. KG

在研机构

Boehringer Ingelheim GmbHC.H. Boehringer Sohn AG & Co. KG

非在研机构-

最高研发阶段临床2期

首次获批日期-

最高研发阶段(中国)无进展

特殊审评-

序列信息

Sequence Code 164717H

来源: *****

Sequence Code 164724L

来源: *****

关联

10

项与 Xentuzumab 相关的临床试验

NCT05110495 / Active, not recruiting早期临床1期IIT

Windows Trial of INsulin-like Growth Factor Neutralising Antibody Xentuzumab in MEN Scheduled for Radical Prostatectomy (WINGMEN)

The WINGMEN trial aims to understand how a hormone-like protein called insulin-like growth factor (IGF) helps prostate cancers grow and become aggressive. IGF is required for normal development, and also helps cancers grow and spread. Men with high blood IGF are at increased risk of developing prostate cancer, and tall men are more likely to get aggressive prostate cancer. The WINGMEN trial will recruit 30 men with prostate cancer who have been offered an operation to remove the prostate. Most men have to wait 4-5 weeks between a decision to have prostate removal surgery, and actually having the operation. In this 4-5 week window we will offer treatment with a new IGF-blocker drug called xentuzumab. The drug is provided by Boehringer Ingelheim and the trial is funded by Prostate Cancer UK.
Xentuzumab will be given as an outpatient by once weekly intravenous infusion (drip) in the Early Phase Clinical Trials Unit, Oxford Cancer Centre, Churchill Hospital. In other trials, xentuzumab is being tested in patients with advanced cancer, and is proving to be well-tolerated. After the 4-week treatment, WINGMEN trial patients will have routine prostate removal surgery. Samples of blood and prostate cancer that are surplus to diagnostic need will be taken from the diagnostic prostate biopsy (pre-xentuzumab) and the cancer removed at surgery (after xentuzumab) for research tests. These samples will be compared to measure how effectively xentuzumab reduces signs of tumour growth, and identify which genes and proteins are switched on or off by xentuzumab, and which may therefore be important in helping IGF promote prostate cancer growth. The information we get from the WINGMEN trial may help us to improve treatment of men with prostate cancer, with the long-term aim of reducing the risk of aggressive prostate cancer

开始日期2021-12-17

申办/合作机构

University of Oxford

[+2]

NCT03659136 / Completed临床2期

XENERA™1: A Multi-centre, Double-blind, Placebo-controlled, Randomised Phase II Trial to Compare Efficacy of Xentuzumab in Combination With Everolimus and Exemestane Versus Everolimus and Exemestane in Women With HR+ / HER2- Metastatic Breast Cancer and Non-visceral Disease

The main objective of the trial is to assess the efficacy of xentuzumab in combination with everolimus and exemestane over everolimus and exemestane in patients with HR+/ HER2- advanced or metastatic breast cancer and non-visceral disease.

开始日期2018-11-28

申办/合作机构

Boehringer Ingelheim GmbH

NCT03099174 / Active, not recruiting临床1期

An Open Label, Phase Ib, Dose-escalation Study Evaluating the Safety and Tolerability of Xentuzumab and Abemaciclib in Patients With Locally Advanced or Metastatic Solid Tumours and in Combination With Endocrine Therapy in Patients With Locally Advanced or Metastatic Hormone Receptor-positive, HER2-, Breast Cancer, Followed by Expansion Cohorts.

This is a study in adult patients with different types of cancer. The purpose of this study is to find a safe dose of:
Xentuzumab in combination with abemaciclib
Xentuzumab in combination with abemaciclib and hormonal therapies The study also tests whether these medicines make tumours shrink in participants with lung and breast cancer.
Participants can stay in the study as long as they benefit from and can tolerate treatment. All participants get xentuzumab infusions and abemaciclib tablets. Participants who have breast cancer get different types of hormonal therapies in addition to xentuzumab and abemaciclib.
For all participants, the size of the tumour is measured regularly. Doctors also regularly check the general health of the participants."

开始日期2017-05-04

申办/合作机构

Boehringer Ingelheim GmbH

100 项与 Xentuzumab 相关的临床结果

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100 项与 Xentuzumab 相关的转化医学

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100 项与 Xentuzumab 相关的专利（医药）

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16

项与 Xentuzumab 相关的文献（医药）

2023-10-01·British journal of cancer

A Phase Ib/II study of IGF-neutralising antibody xentuzumab with enzalutamide in metastatic castration-resistant prostate cancer.

Article

作者: Bianchini, Diletta ; Climent, Miguel Ángel ; de Bono, Johann ; Lord, Simon ; Wang, Shian-Shiang ; Lin, Chia-Chi ; Jones, Robert Hugh ; Bogenrieder, Thomas ; Bailey, Mark ; Macaulay, Valentine M ; Hussain, Syed ; Schlieker, Laura ; Cook, Natalie ; Maroto, José Pablo

BACKGROUNDThis multicentre, open-label, Phase Ib/II trial evaluated the insulin-like growth factor (IGF) 1/2 neutralising antibody xentuzumab plus enzalutamide in metastatic castrate-resistant prostate cancer (mCRPC).METHODSThe trial included Phase Ib escalation and expansion parts and a randomised Phase II part versus enzalutamide alone. Primary endpoints in the Phase Ib escalation, Phase Ib expansion and Phase II parts were maximum tolerated dose (MTD), prostate-specific antigen response and investigator-assessed progression-free survival (PFS), respectively. Patients in the Phase Ib escalation and Phase II parts had progressed on/after docetaxel/abiraterone.RESULTSIn the Phase Ib escalation (n = 10), no dose-limiting toxicities were reported, and xentuzumab 1000 mg weekly plus enzalutamide 160 mg daily (Xe1000 + En160) was defined as the MTD and recommended Phase 2 dose. In the Phase Ib expansion (n = 24), median PFS was 8.2 months, and one patient had a confirmed, long-term response. In Phase II (n = 86), median PFS for the Xe1000 + En160 and En160 arms was 7.4 and 6.2 months, respectively. Subgroup analysis suggested trends towards benefit with Xe1000 + En160 in patients whose tumours had high levels of IGF1 mRNA or PTEN protein. Overall, the combination was well tolerated.CONCLUSIONSXentuzumab plus enzalutamide was tolerable but lacked antitumour activity in unselected patients with mCRPC.CLINICAL TRIAL REGISTRATIONEudraCT number 2013-004011-41.

2023-06-12·Breast cancer research : BCR

XENERA-1: a randomised double-blind Phase II trial of xentuzumab in combination with everolimus and exemestane versus everolimus and exemestane in patients with hormone receptor-positive/HER2-negative metastatic breast cancer and non-visceral disease.

Article

作者: Burris, Howard A ; Blau, Sibel ; Lemieux, Julie ; Biyukov, Tsvetan ; Cortes, Javier ; Neven, Patrick ; Díaz-Redondo, Tamara ; Morales, Serafín ; Joaquim, Ana ; Rugo, Hope S ; Schmid, Peter ; Baktash, Navid ; Massey, Dan ; Hart, Lowell ; Jañez, Noelia Martínez ; García-Sáenz, José Ángel

BACKGROUNDXentuzumab is a humanised monoclonal antibody that binds to IGF-1 and IGF-2, neutralising their proliferative activity and restoring inhibition of AKT by everolimus. This study evaluated the addition of xentuzumab to everolimus and exemestane in patients with advanced breast cancer with non-visceral disease.METHODSThis double-blind, randomised, Phase II study was undertaken in female patients with hormone-receptor (HR)-positive/human epidermal growth factor 2 (HER2)-negative advanced breast cancer with non-visceral disease who had received prior endocrine therapy with or without CDK4/6 inhibitors. Patients received a weekly intravenous infusion of xentuzumab (1000 mg) or placebo in combination with everolimus (10 mg/day orally) and exemestane (25 mg/day orally). The primary endpoint was progression-free survival (PFS) per independent review.RESULTSA total of 103 patients were randomised and 101 were treated (n = 50 in the xentuzumab arm and n = 51 in the placebo arm). The trial was unblinded early due to high rates of discordance between independent and investigator assessment of PFS. Per independent assessment, median PFS was 12.7 (95% CI 6.8-29.3) months with xentuzumab and 11.0 (7.7-19.5) months with placebo (hazard ratio 1.19; 95% CI 0.55-2.59; p = 0.6534). Per investigator assessment, median PFS was 7.4 (6.8-9.7) months with xentuzumab and 9.2 (5.6-14.4) months with placebo (hazard ratio 1.23; 95% CI 0.69-2.20; p = 0.4800). Tolerability was similar between the arms, with diarrhoea (33.3-56.0%), fatigue (33.3-44.0%) and headache (21.6-40.0%) being the most common treatment-emergent adverse events. The incidence of grade ≥ 3 hyperglycaemia was similar between the xentuzumab (2.0%) and placebo (5.9%) arms.CONCLUSIONSWhile this study demonstrated that xentuzumab could be safely combined with everolimus and exemestane in patients with HR-positive/HER2-negative advanced breast cancer with non-visceral disease, there was no PFS benefit with the addition of xentuzumab. Trial registration ClinicalTrials.gov, NCT03659136. Prospectively registered, September 6, 2018.

2023-04-03·Molecular Cancer Therapeutics

Identification ofIGF2as Genomic Driver and Actionable Therapeutic Target in Hepatoblastoma

Article

作者: Morland, Bruce ; Guccione, Ernesto ; Losic, Bojan ; Rialdi, Alex ; Puigvehi, Marc ; Balaseviciute, Ugne ; Del Río-Álvarez, Álvaro ; Peix, Judit ; Sia, Daniela ; Maibach, Rudolf ; Pinyol, Roser ; Cairo, Stefano ; Czauderna, Piotr ; Andreu-Oller, Carmen ; Alaggio, Rita ; Domingo-Sàbat, Montserrat ; Akers, Nicholas K. ; Abril-Fornaguera, Jordi ; Willoughby, Catherine E. ; Torres-Martin, Miguel ; Llovet, Josep M. ; Royo, Laura ; Childs, Margaret ; Mazzaferro, Vincenzo ; Torrens, Laura ; Carrillo-Reixach, Juan ; Armengol, Carolina ; Montironi, Carla ; Haber, Philipp K.

AbstractManagement of hepatoblastoma (HB), the most frequent pediatric liver cancer, is based on surgical resection and perioperative chemotherapy regimens. In this study, we aimed to identify actionable targets in HB and assess the efficacy of molecular therapies in preclinical models of HB. Paired tumor and adjacent tissues from 31 HBs and a validation set of 50 HBs were analyzed using RNA-seq, SNP, and methylation arrays. IGF2 overexpression was identified as the top targetable HB driver, present in 71% of HBs (22/31). IGF2high tumors displayed progenitor cell features and shorter recurrence-free survival. IGF2 overexpression was associated in 91% of cases with fetal promoter hypomethylation, ICR1 deregulation, 11p15.5 loss of heterozygosity or miR483-5p overexpression. The antitumor effect of xentuzumab (a monoclonal antibody targeting IGF1/2) alone or in combination with the conventional therapeutic agent cisplatin was assessed in HB cell lines, in PDX-derived HB organoids and in a xenograft HB murine model. The combination of xentuzumab with cisplatin showed strong synergistic antitumor effects in organoids and in IGF2high cell lines. In mice (n = 55), the combination induced a significant decrease in tumor volume and improved survival compared with cisplatin alone. These results suggest that IGF2 is an HB actionable driver and that, in preclinical models of HB, the combination of IGF1/2 inhibition with cisplatin induces superior antitumor effects than cisplatin monotherapy. Overall, our study provides a rationale for testing IGF2 inhibitors in combination with cisplatin in HB patients with IGF2 overexpression.

100 项与 Xentuzumab 相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
-	-	-	DB14871

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
转移性乳腺癌	临床2期	德国	Boehringer Ingelheim GmbH	2018-11-28
转移性乳腺癌	临床2期	美国	Boehringer Ingelheim GmbH	2018-11-28
转移性乳腺癌	临床2期	加拿大	Boehringer Ingelheim GmbH	2018-11-28
转移性乳腺癌	临床2期	葡萄牙	Boehringer Ingelheim GmbH	2018-11-28
转移性乳腺癌	临床2期	意大利	Boehringer Ingelheim GmbH	2018-11-28
转移性乳腺癌	临床2期	英国	Boehringer Ingelheim GmbH	2018-11-28
非小细胞肺癌	临床2期	-	C.H. Boehringer Sohn AG & Co. KG	-
前列腺癌	临床2期	-	C.H. Boehringer Sohn AG & Co. KG	-
乳腺癌	临床前	奥地利	Boehringer Ingelheim GmbH	2014-04-01
乳腺癌	临床前	爱尔兰	Boehringer Ingelheim GmbH	2014-04-01

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临床结果

适应症

分期

评价

查看全部结果

研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT02191891 (WCLC2016)	临床1期	非小细胞肺癌	16	BI 836845 1,000mg/week + afatinib 30mg/day	(選鑰鏇觸艱繭鏇壓壓積) = 繭鹹夢鹹醖鏇夢鹽願壓構觸艱獵壓鬱齋餘餘艱 (築製衊夢蓋憲顧衊願顧 )	-	2016-12-07
				BI 836845 1,000mg/week + afatinib 40mg/day	(選鑰鏇觸艱繭鏇壓壓積) = 衊築夢鑰構鑰遞艱糧遞構觸艱獵壓鬱齋餘餘艱 (築製衊夢蓋憲顧衊願顧 )
NCT02123823 (Study 1280.4, ASCO2016)	临床1/2期	HR阳性乳腺癌	24	BI 836845 1000mg	(獵鹽積鬱構窪憲蓋鹹憲) = 餘築鑰觸夢簾夢鬱簾構夢壓艱遞鏇鑰積衊憲鑰 (醖鹹餘衊糧範網鹹齋獵 ) 更多	积极	2016-05-20
NCT03659136 (XENERA-1, Pubmed)	临床2期	HR阳性/HER2阴性乳腺癌	103	Xentuzumab	(獵夢範簾構憲觸淵鏇願) = 廠積積糧獵願鬱糧衊構選築築網鑰淵鑰觸艱繭 (繭鬱積艱鑰積願網壓糧, 6.8 ~ 29.3) 更多	不佳	2023-06-12
				Placebo	(獵夢範簾構憲觸淵鏇願) = 醖憲衊顧膚範夢壓鏇積選築築網鑰淵鑰觸艱繭 (繭鬱積艱鑰積願網壓糧, 7.7 ~ 19.5) 更多
NCT03099174 (ASCO2021)	临床1期	HR阳性/HER2阳性乳腺癌	64	Xentuzumab	(鹹齋鹹齋蓋鏇餘築鹽選) = 鏇願築遞鬱築製餘夢網獵遞淵鏇鏇壓憲衊鏇積 (夢襯醖鬱鹹鬱餘襯鏇夢 )	-	2021-05-28
				Abemaciclib	(鹹齋鹹齋蓋鏇餘築鹽選) = 鏇網製壓選齋襯餘範膚獵遞淵鏇鏇壓憲衊鏇積 (夢襯醖鬱鹹鬱餘襯鏇夢 )
AACR2020	临床1期	非小细胞肺癌二线	25	Xentuzumab 1000 mg weekly + Abemaciclib 150 mg Q12h	(醖憲齋範艱醖夢艱艱顧) = 餘獵艱鬱願遞淵醖獵鏇膚觸願窪膚膚製襯壓範 (襯選餘鹽襯願製鏇窪顧, 1.2 ~ 5.3)	积极	2020-08-15
NCT02145741 (Pubmed \| Cancer Sci) 人工标引	临床1期	实体瘤	21	xentuzumab	(簾鬱糧築願獵觸齋繭餘) = There were no dose-limiting toxicities at any dose. 糧淵願淵糧選窪膚鏇夢 (觸顧憲繭齋顧鹽鑰餘網 ) 更多	积极	2021-12-06
NCT02123823 (Pubmed) 人工标引	临床1/2期	HR阳性HER2阴性淋巴结阳性乳腺癌 HR positive \| HER2-negative	140	exemestane+everolimus+xentuzumab	(鬱鑰鏇鹹憲遞顧築簾選) = 壓蓋淵廠餘衊遞繭顧夢膚遞廠窪鏇鹽餘顧觸鑰 (積鹹構願夢衊窪窪艱糧, 3.3 ~ NR)	不佳	2021-01-15
				exemestane+everolimus	(鬱鑰鏇鹹憲遞顧築簾選) = 鬱糧廠顧鏇廠糧壓襯糧膚遞廠窪鏇鹽餘顧觸鑰 (積鹹構願夢衊窪窪艱糧, 3.7-9.1)
NCT02204072 (ASCO2019) 人工标引	临床2期	转移性去势抵抗性前列腺癌	86	enzalutamide+xentuzumab	(遞願範夢襯構遞築窪構) = 願範選壓鹹夢衊鬱憲鹹願製構夢願襯觸構繭觸 (獵製憲壓憲糧夢網遞繭, 3.5 ~ 8.7) 更多	不佳	2019-06-01
				enzalutamide	(遞願範夢襯構遞築窪構) = 鏇獵壓齋衊選憲襯醖鏇願製構夢願襯觸構繭觸 (獵製憲壓憲糧夢網遞繭, 3.5 ~ 11.1) 更多
NCT02191891 (Pubmed) 人工标引	临床1期	EGFR-T790M 突变非小细胞肺癌 EGFR Positive \| EGFR T790M Negative	32	Afatinib+Xentuzumab (part A)	(構糧鏇壓構網夢網糧鹹) = Maximum tolerated dose was xentuzumab 1000 mg/wk plus afatinib 40 mg/d. 鏇鏇餘衊積膚糧鹹鑰膚 (鑰鏇糧窪襯觸糧廠簾鑰 ) 更多	不佳	2021-07-10
				Afatinib+Xentuzumab (part B)
NCT01317420 \| NCT01403974 (Study 1280.1 \| Study 1280.2, Pubmed \| Med J Aust)	临床1期	晚期恶性实体瘤 \| 恶性实体肿瘤	-	Xentuzumab	艱鑰醖範築蓋淵網網遞(齋願鏇淵選積選蓋膚繭) = 衊製齋夢衊壓願壓蓋願築鑰獵構願鬱願窪壓鑰 (選蓋淵簾鬱鹹鏇鹽衊膚 )	-	2020-04-01