Xentuzumab(Xentuzumab) - 药物靶点：IGF-1 x IGF-2_在研适应症：HR阳性/HER2阳性乳腺癌，转移性去势抵抗性前列腺癌，晚期恶性实体瘤_专利_临床

概要

基本信息

药物类型

双特异性抗体

别名

BI-836845

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

肿瘤皮肤和肌肉骨骼疾病泌尿生殖系统疾病

在研适应症

HR阳性/HER2阳性乳腺癌转移性去势抵抗性前列腺癌晚期恶性实体瘤+ [2]

非在研适应症

EGFR突变的非小细胞肺癌ER阳性乳腺癌HR阳性/HER2阴性乳腺癌+ [2]

原研机构

C.H. Boehringer Sohn AG & Co. KG

在研机构

Boehringer Ingelheim GmbH

非在研机构-

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

Sequence Code 164717H

来源: *****

Sequence Code 164724L

来源: *****

关联

10

项与 Xentuzumab 相关的临床试验

NCT05110495

/ Completed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

EUCTR2017-003131-11-BE

/ Not yet recruiting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

开始日期2018-11-26

申办/合作机构

SCS Boehringer Ingelheim Comm.V

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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17

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

BACKGROUND:

This 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).

METHODS:

The 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.

RESULTS:

In 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.

CONCLUSIONS:

Xentuzumab plus enzalutamide was tolerable but lacked antitumour activity in unselected patients with mCRPC.

CLINICAL TRIAL REGISTRATION:

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

BACKGROUND:

Xentuzumab 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.

METHODS:

This 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.

RESULTS:

A 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.

CONCLUSIONS:

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

Abstract:

Management 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.

1

项与 Xentuzumab 相关的新闻（医药）

2024-06-30

·生物制药小编

肥胖促癌：“3个紊乱”

至少13种肿瘤与肥胖相关（ N Engl J Med 375, 794–798）。 N Engl J Med 375, 794–798 第1乱：胰岛素和雌激素信号紊乱胰岛素受体有两个亚型，IR-A和IR-B，以不同的比例存在于不同的组织中，执行不同的功能。 IR-A在生命早期主要具有促进有丝分裂的作用，它在成年期的表达与胰岛素抵抗和不受调节的细胞增殖有关。IR-B在肝脏和其他成人组织中表达，并主要参与葡萄糖代谢。高水平的IR-A与肿瘤的发生有关，并在多种癌症中被发现，包括乳腺癌、子宫内膜癌、结肠癌和肝细胞癌。与IR-B相比，IR-A对IGF表现出更高的亲和力。IGF-1和IGF-2是在肝脏中响应生长激素而合成的小肽。虽然胰岛素主要以自由形式循环，但IGFs主要与IGF结合蛋白(IGFBPs)结合而循环，从而调节其水平和生物学功能。IGF-1和IGF-2通过与IGF-1受体(IGF-1R)结合，促进细胞生长和增殖，多项研究表明，IGF-1R在乳腺癌和子宫内膜癌中的表达增加。在肥胖的情况下，较高水平的IGF-2同时刺激IGF-1R和IR-A表达。 British Journal of Cancer (2021)125:495–509 肥胖患者，胰岛素和IGFR长期被激活，导致细胞中葡萄糖摄取增加、细胞增殖、血管生成，并最终产生恶性转化和恶性生长的潜力。内脏肥胖（非皮下脂肪肥胖）是比BMI更好的肿瘤风险预测因子。因为内脏肥胖会增加循环的游离脂肪酸，进而增加高胰岛素血症和胰岛素抵抗的发生，增加促炎细胞因子分泌，引起胰岛素受体和IGFR的过度激活，增加PI3K活化，促进肿瘤增殖。临床前模型中，PI3K抑制后，胰岛素的激增可以重新激活这一通路，并刺激进一步的肿瘤细胞增殖。药物靶点：IGF、IR-A、IGF1R、酪氨酸激酶。存在的问题：鉴于IR和IGF1R在人体组织中的普遍存在性，靶向这些受体，会产生off-tumor的相关的毒性。同时阻断IGF1R和IR可导致剂量限制性高血糖，仅抑制IGF1R可导致IR信号通路的代偿性激活。药物举例： IGFR Figitumumab Figitumumab是辉瑞研发的IGF1R单克隆抗体，与卡铂和紫杉醇联合治疗晚期非小细胞肺癌(NSCLC)。然而，由于严重不良事件的发生率增加，包括3/4级高血糖和与治疗相关的死亡，临床试验提前结束。 Linsitinib（OSI-906） Astellas Pharma研发的小分子抑制剂，靶向IGF1R and IR, 3期临床（ NCT00924989）治疗局部晚期或转移性肾上腺皮质癌，和对照组比较，无明显临床获益。没有新的临床研究开展。 IGF2 Dusigitumab/MEDI-573 Dusigitumab由MedImmune LLC研发，IgG2λ抗体，靶向IGF-2 和IGF-1，1期临床（NCT00816361，NCT01340040），最好的结果是疾病稳定（SD），未出现完全缓解（CR）或者部分缓解（PR）。没有新的临床研究开展。 Xentuzumab/BI836845 由Boehringer Ingelheim研发，IgG1抗体，结合IGF-2 和IGF-1，首次人体临床试验（NCT01403974; NCT01317420），显示耐受性良好，125例病人出现2例PR。16例EGFR突变的NSCLC患者（NCT02191891），Afatinib 联合Xentuzumab (BI 836845) Phase1b，没有出现PR，10例SD。NCT02123823，将xentuzumab 加入 everolimus/exemestane，治疗HER2阴性，雌激素受体阳性患者，没有改善PFS，但在没有内脏转移的患者中，观察到了PFS改善，随后开展2期临床XENERA™-1 (NCT03659136)。改变糖稳态重新利用治疗糖尿病的药物在癌症研究领域取得一些进展。二甲双胍在临床前模型中，二甲双胍可下调IGF信号通路，抑制子宫浆液性癌细胞的增殖。二甲双胍还能减弱乳腺癌、肺癌和胰腺癌细胞中IGF1的表达以及mTOR和Akt（胰岛素信号传导的下游效应因子）的激活。在乳腺癌的新辅助治疗中，二甲双胍与其他细胞毒性药物联合使用，改善了病理完全缓解率，但没有改善转移性患者的PFS。用二甲双胍抑制IGF1和PI3K信号通路可以降低子宫内膜肿瘤中的细胞增殖。在small window-of-opportunity（术前）试验中，二甲双胍降低了患者的肿瘤增殖(标记Ki-67)11.75%(P=0.008)，在另一项试验中降低了17.2%(P=0.002)，但这些发现在验证性3期试验中没有得到重复。第2乱：脂肪因子信号通路紊乱脂肪组织分泌的脂肪因子（激素和细胞因子）失调是过度肥胖的一个标志，可以促进肿瘤的生长。瘦素（leptin），脂肪细胞分泌的激素和肥胖的生物标志物，主要功能是下丘脑介导的食欲调节，它调节进食行为和能量消耗。肥胖个体的循环瘦素水平升高，并与癌症发展和进展的风险增加有关，如子宫内膜癌、乳腺癌、结肠癌和肾癌等。瘦素与瘦素受体结合，激活多个信号通路，包括JAK/STAT、MAPK和PI3K通路，最终促进细胞增殖。通过瘦素受体传递的信号也能激活乳腺癌干细胞，是其存活和维持所必需的。胰岛素和IGF1也可以增加乳腺上皮组织中瘦素及其受体的表达，这种表达的增加与乳腺癌预后较差有关。瘦素可以刺激血管生成，增加血管通透性，使恶性细胞进一步生长。因此，瘦素是肿瘤和肿瘤微环境(TME)之间相互作用的重要中介物。 British Journal of Cancer (2021) 125:495–509 另一种由脂肪细胞分泌的激素是脂联素(adiponectin)，它具有抗糖尿病和抗炎的特性。肥胖和代谢综合征血浆脂联素水平降低，脂联素受体(AdipoR1和AdipoR2)的表达也降低，导致脂联素敏感性进一步降低。低脂联素水平与胰岛素抵抗和肥胖相关恶性肿瘤的风险增加有关，包括乳腺癌和子宫内膜癌。脂联素激活AMPK通路，导致p53和p21的上调，从而调控细胞周期和凋亡。肥胖增加瘦素，降低脂联素水平，瘦素/脂联素比值被认为是乳腺癌生长的一个预测因子。其他脂肪因子的水平，如抵抗素（resistin）和内脂肪素（visfatin），在肥胖人体升高，是炎症的标志物，与各种癌症的发展和进展有关。抵抗素（resistin）被认为通过TLR4介导NF-κB和STAT3的激活来促进乳腺癌细胞的生长。药物靶点瘦素虽然瘦素和肿瘤发生发展的关系已经确定，但是目前尚无拮抗瘦素的药物进入临床。PEG-LPrA2是一种瘦素受体拮抗剂，已在三阴性乳腺癌的临床前模型中被研究，可以抑制瘦素信号通路并抑制乳腺癌的生长。脂联素 PPAR合成配体（罗格列酮和吡格列酮），是糖尿病治疗药物，通过调节葡萄糖代谢、减少高胰岛素血症和改变脂肪酸代谢。此外，PPARγ合成配体已被证明在临床前模型和人体研究，显示增加脂联素水平，可能有利于治疗肥胖驱动的癌症。 Statins 他汀类药物被广泛用于脂质水平管理，也可能具有抗癌特性。已经提出了几种抗癌机制的作用：通过抑制Ras和Rho激活，损害肿瘤细胞增殖；通过细胞周期阻滞抑制细胞增殖；诱导凋亡；剂量依赖性抑制血管生成；适当抗炎。但是临床结果并不一致。第3乱：雌激素信号紊乱 British Journal of Cancer (2021)125:495–509 绝经后，雌激素主要来自于雄激素转化（通过雌激素生物合成酶，芳香化酶）。肥胖引起癌症发生的一个重要因素就是增加脂肪组织中芳香化酶活性。芳香化酶抑制剂二甲双胍已被确定为一种潜在的乳腺特异性芳香化酶抑制剂。脂肪因子adiponectin和ghrelin也被证明以启动子特异性的方式抑制芳香化酶的表达，这可能有助于解释肥胖环境下低水平脂联素与乳腺癌生长之间的联系。特异性甾体和非甾体芳香化酶抑制剂已证明对预防和治疗ER+乳腺癌有效，ER+乳腺癌发展或复发的风险降低约50%。芳香化酶抑制剂也可能在ER+子宫内膜癌中有临床应用，但目前临床疗效有限。 Anastrozole是一种非甾体芳香化酶抑制剂，已被证明在新辅助治疗中可减少子宫内膜癌细胞的增殖，并对治疗复发性ER+子宫内膜癌具有一定的活性。 Trozole（非甾体芳香化酶抑制剂）联合everolimus（mTOR抑制剂），未被选择的子宫内膜癌人群中，总有效率为32%。 Exemestane一种不可逆的甾体芳香化酶抑制剂，目前正在被测试用于治疗子宫内膜增生和低级别子宫内膜癌(NCT03300557)。其他正在进行的试验，正在评估芳香化酶抑制剂与PI3K-mTOR通路抑制剂的各种组合(NCT02730923，NCT03008408)。饮食控制及体育锻炼饮食控制和体育锻炼，可以显著改善机体的炎症因子水平，恢复机体代谢稳态。国内和国际上，都有一些临床试验在评估其价值。主要参考文献 Lauby-Secretan B, Scoccianti C, Loomis D,Grosse Y, Bianchini F & Straif K (2016) Body fatness and cancer – viewpointof the IARC Working Group. N Engl J Med 375, 794–798 Johann de Bono et al, Two first-in-humanstudies of xentuzumab, a humanised insulin-like growth factor(IGF)-neutralising antibody,in patients with advance）dsolid tumours，British Journal of Cancer https://doi.org/10.1038/s41416-020-0774-1 Goodwin, P., Ennis, M., Cescon, D., Elser,C., Haq, R., Hamm, C. et al. Abstract P1- 16-03: phase II randomized clinicaltrial (RCT) of metformin (MET) vs placebo (PLAC) in combination withchemotherapy (CXT) in refractory locally advanced (LABC) or metastatic breastcancer (MBC). Cancer Res. 79, P1-16-03–P11-16-03 (2019) Maria M. Rubinstein, Kristy A. Brown andNeil . Iyengar. Targeting obesity-related dysfunction in hormonally drivencancers. British Journal of Cancer (2021) 125:495–50

临床结果临床2期

100 项与 Xentuzumab 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
HR阳性/HER2阴性乳腺癌	临床2期	美国	Boehringer Ingelheim GmbH	2018-11-28
HR阳性/HER2阴性乳腺癌	临床2期	澳大利亚	Boehringer Ingelheim GmbH	2018-11-28
HR阳性/HER2阴性乳腺癌	临床2期	比利时	Boehringer Ingelheim GmbH	2018-11-28
HR阳性/HER2阴性乳腺癌	临床2期	加拿大	Boehringer Ingelheim GmbH	2018-11-28
HR阳性/HER2阴性乳腺癌	临床2期	法国	Boehringer Ingelheim GmbH	2018-11-28
HR阳性/HER2阴性乳腺癌	临床2期	德国	Boehringer Ingelheim GmbH	2018-11-28
HR阳性/HER2阴性乳腺癌	临床2期	希腊	Boehringer Ingelheim GmbH	2018-11-28
HR阳性/HER2阴性乳腺癌	临床2期	意大利	Boehringer Ingelheim GmbH	2018-11-28
HR阳性/HER2阴性乳腺癌	临床2期	葡萄牙	Boehringer Ingelheim GmbH	2018-11-28
HR阳性/HER2阴性乳腺癌	临床2期	西班牙	Boehringer Ingelheim GmbH	2018-11-28

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临床结果

适应症

分期

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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


NCT05110495 (WINGMEN, CTgov)	早期临床1期	前列腺癌 \| 遗传性前列腺癌7型 \| 前列腺腺癌	27	Xentuzumab	襯製衊製鹽鏇鹽範壓構(淵鏇構構繭鹽憲鑰襯遞) = 繭糧窪蓋築夢衊鹹襯醖願鬱範襯觸鹽顧壓鑰夢 (遞築憲鬱範艱夢願製選, 簾鬱衊網鬱淵範鏇鏇淵 ~ 淵鏇願襯繭構鬱糧獵構) 更多	-	2025-02-17
NCT03659136 (XENERA-1, CTgov)	临床2期	转移性乳腺癌 \| HR阳性/HER2阴性乳腺癌	103	Exemestane+Everolimus+Xentuzumab (1000 mg Xentuzumab + 10 mg Everolimus + 25 mg Exemestane)	蓋鑰蓋鏇襯壓夢鹹遞憲(構蓋願鬱網蓋選鬱膚醖) = 繭遞獵構夢觸夢築簾糧淵築窪醖鑰膚鬱襯選憲 (積夢遞製艱襯繭構艱憲, 糧選簾網網製遞繭築淵 ~ 獵顧蓋蓋鏇顧鑰積膚餘) 更多	-	2022-09-29
				Placebo+Exemestane+Everolimus (Placebo + 10 mg Everolimus + 25 mg Exemestane)	蓋鑰蓋鏇襯壓夢鹹遞憲(構蓋願鬱網蓋選鬱膚醖) = 襯窪憲觸糧鑰鬱範襯鏇淵築窪醖鑰膚鬱襯選憲 (積夢遞製艱襯繭構艱憲, 襯鏇齋築築衊齋獵鏇鬱 ~ 鹽製積窪鏇廠簾夢餘顧) 更多
NCT02145741 (Pubmed \| Cancer Sci) 人工标引	临床1期	实体瘤	21	xentuzumab	廠衊簾艱窪鹽壓鹽廠餘(夢願簾選範觸網獵鹹廠) = There were no dose-limiting toxicities at any dose. 遞蓋壓獵壓襯築願觸鑰 (鏇顧糧夢襯築餘鑰襯醖 ) 更多	积极	2021-12-06
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)	築壓鹽願鬱齋觸鏇糧鬱(壓衊壓襯膚餘鹹醖憲鏇) = Maximum tolerated dose was xentuzumab 1000 mg/wk plus afatinib 40 mg/d. 蓋襯鑰糧築襯獵選願憲 (簾遞築範壓簾鑰膚糧網 ) 更多	不佳	2021-07-10
				Afatinib+Xentuzumab (part B)
NCT03099174 (ASCO2021)	临床1期	HR阳性/HER2阳性乳腺癌	64	Xentuzumab	襯廠觸憲顧鹽簾鏇廠壓(淵膚蓋獵遞築壓淵壓遞) = 淵簾鹽艱網艱願簾顧積廠繭獵範獵遞願衊選夢 (廠廠夢廠顧憲襯鑰製糧 )	-	2021-05-28
				Abemaciclib	襯廠觸憲顧鹽簾鏇廠壓(淵膚蓋獵遞築壓淵壓遞) = 製窪夢窪夢鑰願膚夢膚廠繭獵範獵遞願衊選夢 (廠廠夢廠顧憲襯鑰製糧 )
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	糧膚襯鹽衊廠網艱窪廠(襯齋壓醖選遞壓餘鬱繭) = 壓鏇獵簾鹹膚憲醖襯衊構範憲醖醖鏇憲願壓範 (鹽齋築襯壓製顧夢艱繭, 3.3 ~ NR)	不佳	2021-01-15
				exemestane+everolimus	糧膚襯鹽衊廠網艱窪廠(襯齋壓醖選遞壓餘鬱繭) = 憲鹹夢窪構膚願膚鏇選構範憲醖醖鏇憲願壓範 (鹽齋築襯壓製顧夢艱繭, 3.7 ~ 9.1)
AACR2020	临床1期	非小细胞肺癌二线	25	Xentuzumab 1000 mg weekly + Abemaciclib 150 mg Q12h	製鏇鬱壓獵廠鑰夢夢膚(積糧蓋鑰鹹醖鬱簾夢簾) = 廠鹹壓築鹽蓋夢鏇製窪餘醖獵鏇鬱壓憲積獵餘 (窪鑰積醖醖遞選壓膚鹹, 1.2 ~ 5.3)	积极	2020-08-15
NCT02204072 (ASCO 12019 \| ASCO 22019) 人工标引	临床2期	转移性去势抵抗性前列腺癌	86	enzalutamide+xentuzumab	積顧築膚夢網膚願簾積(獵構積壓廠製願壓築製) = 廠衊製壓齋廠齋襯遞齋蓋觸艱艱窪鬱衊醖築簾 (襯製鹹範構夢鹽顧襯網, 3.5 ~ 8.7) 更多	不佳	2019-06-01
				enzalutamide	積顧築膚夢網膚願簾積(獵構積壓廠製願壓築製) = 鹹蓋衊鑰簾淵鹽蓋範製蓋觸艱艱窪鬱衊醖築簾 (襯製鹹範構夢鹽顧襯網, 3.5 ~ 11.1) 更多
NCT02123823 (Study 1280.4, ASCO2016)	临床1/2期	HR阳性乳腺癌	24	BI 836845 1000mg	積鹹築窪鬱繭顧鬱築淵(膚築願糧壓願願獵選鏇) = 餘願膚簾築積糧窪餘齋襯願淵鏇願觸艱鬱壓觸 (廠衊鹹鹹醖餘膚範醖網 ) 更多	积极	2016-05-20
NCT01403974 (ASCO2014)	临床1期	晚期恶性实体瘤	48	BI 836845	製膚積鏇襯餘觸壓蓋壓(衊製觸鏇積餘獵廠夢廠) = 鹹廠構鬱構醖齋壓繭願憲蓋繭鏇壓範製憲鹽餘 (壓廠壓襯襯鬱夢壓襯淵 ) 更多	-	2014-05-20