更新于：2024-11-01

VEGFR3

更新于：2024-11-01

基本信息

别名

Feline McDonough Sarcoma (FMS)-like tyrosine kinase 4、FLT-4、FLT4

+ [12]

简介

Tyrosine-protein kinase that acts as a cell-surface receptor for VEGFC and VEGFD, and plays an essential role in adult lymphangiogenesis and in the development of the vascular network and the cardiovascular system during embryonic development. Promotes proliferation, survival and migration of endothelial cells, and regulates angiogenic sprouting. Signaling by activated FLT4 leads to enhanced production of VEGFC, and to a lesser degree VEGFA, thereby creating a positive feedback loop that enhances FLT4 signaling. Modulates KDR signaling by forming heterodimers. The secreted isoform 3 may function as a decoy receptor for VEGFC and/or VEGFD and play an important role as a negative regulator of VEGFC-mediated lymphangiogenesis and angiogenesis. Binding of vascular growth factors to isoform 1 or isoform 2 leads to the activation of several signaling cascades; isoform 2 seems to be less efficient in signal transduction, because it has a truncated C-terminus and therefore lacks several phosphorylation sites. Mediates activation of the MAPK1/ERK2, MAPK3/ERK1 signaling pathway, of MAPK8 and the JUN signaling pathway, and of the AKT1 signaling pathway. Phosphorylates SHC1. Mediates phosphorylation of PIK3R1, the regulatory subunit of phosphatidylinositol 3-kinase. Promotes phosphorylation of MAPK8 at 'Thr-183' and 'Tyr-185', and of AKT1 at 'Ser-473'.

关联

项与 VEGFR3 相关的药物

Fruquintinib

呋喹替尼

靶点

VEGFR1 x VEGFR2 x VEGFR3

作用机制

VEGFR1拮抗剂 [+2]

在研机构

原研机构

在研适应症

非在研适应症

最高研发阶段批准上市

首次获批国家/地区

中国

首次获批日期2018-09-04

Anlotinib Dihydrochloride

盐酸安罗替尼

靶点

FGFRs x PDGFR x VEGFR1 x VEGFR2 x VEGFR3 x c-Kit

作用机制

FGFRs拮抗剂 [+6]

在研机构

正大天晴药业集团股份有限公司 [+2]

原研机构

Advenchen Laboratories LLC

在研适应症

广泛期小细胞肺癌 [+53]

非在研适应症

肢端雀斑恶性黑色素瘤 [+28]

最高研发阶段批准上市

首次获批国家/地区

中国

首次获批日期2018-05-08

Tivozanib

替沃扎尼

靶点

PDGFRβ x VEGFR1 x VEGFR2 x VEGFR3 x c-Kit

作用机制

PDGFRβ抑制剂 [+4]

在研机构

AVEO Pharmaceuticals, Inc. [+3]

原研机构

Kyowa Kirin Co., Ltd.

在研适应症

肾细胞癌 [+5]

非在研适应症

晚期肝细胞癌 [+10]

最高研发阶段批准上市

首次获批国家/地区

欧盟 [+3]

首次获批日期2017-08-24

3,797

项与 VEGFR3 相关的临床试验

NCT05077215 / Not yet recruiting临床3期

A Phase 3, Randomized, Open-Label, Active-Controlled, Superiority Trial of EG007, Added to the Combination of Lenvatinib Plus Pembrolizumab Vs. Lenvatinib Plus Pembrolizumab in Patients with Advanced Endometrial Cancer

This is a Phase 3, multicenter, randomized, open-label trial to evaluate whether EG-007 plus Len+Pem is superior to Len+Pem alone in patients with advanced endometrial cancer (Stage III or IV). This trial will be preceded by a safety lead-in study with up to 28 patients (the safety lead-in is a separate, free-standing protocol).
Approximately 450 patients will be randomized equally (1:1) to receive EG-007 plus Len+Pem or Len+Pem alone. The randomization will be stratified by the following stratification factors:
* Diagnosis Classification (advanced Stage III/IV vs. recurrent endometrial cancer)
* ECOG score at baseline (0 vs 1)
* Geographic region (Asia vs ROW)

开始日期2025-12-01

申办/合作机构

Evergreen Therapeutics, Inc

NCT05106127 / Not yet recruiting临床2期

A Phase 2, Open-Label, Safety Lead-In with Long Term Safety Study of EG-007, Added to the Combination of Lenvatinib Plus Pembrolizumab

This is a Phase 2 trial Safety Lead-in trial conducted in 3 cohorts of patients.
A safety lead-in study of the impact of adding the Repurposed Drugs a third agent will be conducted prior to opening enrollment into the compassionate use study. All patients enrolled in the safety lead-in study may continue long-term treatment under this protocol without interruption of dosing.

开始日期2025-08-01

申办/合作机构

Evergreen Therapeutics, Inc

NCT05690035 / Withdrawn临床2期IIT

PD-1 Antibody (Tislelizumab) Combined With VEGFR 1/2/3 Inhibitor (Fruquintinib) for ARID1A-mutated Metastatic pMMR/MSS Colorectal Cancer: an Open-label, Multi-center, Phase II Clinical Trial

This is an open-label phase II study, with the aim of investigating the efficacy and safety of Tislelizumab + Fruquintinib combination therapy in ARID1A-mutated pMMR/MSS metastatic colorectal cancer who have been treated with standard chemotherapy that includes fluoropyrimidine, oxaliplatin, and irinotecan. Patients with hypermutated CRC that carries POLE/POLD1 mutations cannot be included.

开始日期2025-07-01

申办/合作机构

中山大学

[+2]

100 项与 VEGFR3 相关的临床结果

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100 项与 VEGFR3 相关的转化医学

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0 项与 VEGFR3 相关的专利（医药）

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2,620

项与 VEGFR3 相关的文献（医药）

2025-01-01·International Journal of Hygiene and Environmental Health

Associations between metal/metalloid exposure during pregnancy and placental growth characteristics: Findings from the Hangzhou birth cohort study II

Article

作者: Zhou, Jiena ; Zhong, Kunhong ; Tang, Jun ; Huang, Kegui ; Luo, Qiong ; Xu, Yang ; Jin, Lanfei ; Zhao, Hao ; Zhang, Dan ; Chen, Guangdi ; Zhu, Qinheng ; Zhou, Yexinyi ; Guo, Jing

Previous studies have suggested that metal/metalloid (hereafter referred to as metal) exposure may influence placental growth by affecting gene expression in the placenta. However, no epidemiological studies have been conducted to validate the relationships between metals exposure, placental gene expression, and placental growth at the population level. This study aims to investigate these relationships based on Hangzhou birth cohort study II (HBCS-II). Totally, 1025 participants were derived from HBCS-II. Thirteen metals levels in the placenta were measured using inductively coupled plasma mass spectrometry. Placental growth characteristics were assessed, including placental weight, chorionic disc area, placental eccentricity, and distance from cord insertion site to the nearest edge of placenta (DCIEP). The relationships between metals exposure and placental growth characteristics were examined using the elastic net model combined unpenalized linear regression model. Placental gene expression levels were analyzed through RNA sequencing and real-time polymerase chain reaction (RT-qPCR), and mediation analysis was conducted to investigate whether placental gene expression could mediate the relationship between metal exposure and placental growth. Notably, the results showed that a unite increase in Ln-transformed cadmium (Cd) levels was associated with a reduction of 16.4 g [95% confidence interval (CI): 31.2, -1.5] in placental weight, 13.9 cm² (95%CI: 20.0, -7.8) in chorionic disc area, and 0.3 cm (95%CI: 0.55, -0.06) in DCIEP. Through RNA sequencing followed by validation, significant associations were observed between placental Cd level and increased expression of placental genes, including TNFAIP2, OLAH, FLT4, SH3PXD2A, LIMCH1, BCL6, SLCO2A1, and CPSF1. Additionally, increased placental TNFAIP2, OLAH, FLT4, SH3PXD2A and LIMCH1 expression was linked to reduced placental weight. Moreover, SH3PXD2A was associated with decreased chorionic disc area. Mediation analysis showed that placental Cd level was associated with a 12.0 g (95%CI: 23.8, -2.7) decrease in placental weight mediated through the upregulation of FTL4 gene expression. The study provides evidence of the association between placental Cd exposure and decreased placental weight, and the FLT4 gene may play a mediating role in this relationship. Future experiment studies should be performed to validate the results.

2024-12-01·Cellular and Molecular Life Sciences

VEGFD signaling balances stability and activity-dependent structural plasticity of dendrites

Article

作者: Mauceri, Daniela ; Missirlis, Dimitris ; Sánchez Romero, Javier ; Yan, Jing ; Aksan, Bahar ; Kenkel, Ann-Kristin

AbstractMature neurons have stable dendritic architecture, which is essential for the nervous system to operate correctly. The ability to undergo structural plasticity, required to support adaptive processes like memory formation, is still present in mature neurons. It is unclear what molecular and cellular processes control this delicate balance between dendritic structural plasticity and stabilization. Failures in the preservation of optimal dendrite structure due to atrophy or maladaptive plasticity result in abnormal connectivity and are associated with various neurological diseases. Vascular endothelial growth factor D (VEGFD) is critical for the maintenance of mature dendritic trees. Here, we describe how VEGFD affects the neuronal cytoskeleton and demonstrate that VEGFD exerts its effects on dendrite stabilization by influencing the actin cortex and reducing microtubule dynamics. Further, we found that during synaptic activity-induced structural plasticity VEGFD is downregulated. Our findings revealed that VEGFD, acting on its cognate receptor VEGFR3, opposes structural changes by negatively regulating dendrite growth in cultured hippocampal neurons and in vivo in the adult mouse hippocampus with consequences on memory formation. A phosphoproteomic screening identified several regulatory proteins of the cytoskeleton modulated by VEGFD. Among the actin cortex-associated proteins, we found that VEGFD induces dephosphorylation of ezrin at tyrosine 478 via activation of the striatal-enriched protein tyrosine phosphatase (STEP). Activity-triggered structural plasticity of dendrites was impaired by expression of a phospho-deficient mutant ezrin in vitro and in vivo. Thus, VEGFD governs the equilibrium between stabilization and plasticity of dendrites by acting as a molecular brake of structural remodeling.

2024-11-01·Arthritis & Rheumatology

ERG Regulates Lymphatic Vessel Specification Genes and Its Deficiency Impairs Wound Healing‐Associated Lymphangiogenesis

Article

作者: Chakraborty, Adri ; Bujor, Andreea ; Gritli, Sami ; Yamashita, Takashi ; Browning, Jeffrey L. ; Trojanowski, Marcin ; Trojanowska, Maria ; Roh, Daniel ; Kaplan, Ulas ; Ligresti, Giovanni ; Browning, Jeffrey L ; Marden, Grace

ObjectiveRarefaction of blood and lymphatic vessels in the skin has been reported in systemic sclerosis (SSc) (scleroderma). E26 transformation–specific–related factor (ERG) and Friend leukemia virus–induced erythroleukemia 1 (FLI‐1) are important regulators of angiogenesis, but their role in lymphatic vasculature is lesser known. The goal of this study was to determine the role of ERG and FLI‐1 in postnatal lymphangiogenesis and SSc lymphatic system defects.MethodsImmunofluorescence was used to detect ERG and FLI‐1 in skin biopsy samples from patients with SSc and healthy controls. Transcriptional analysis of ERG or FLI‐1–silenced human dermal lymphatic endothelial cells (LECs) was performed using microarrays. Effects of ERG and FLI‐1 deficiency on in vitro tubulogenesis in human dermal LECs were examined using a Matrigel assay. ERG and FLI‐1 endothelial–specific knockouts and ERG lymphatic–specific knockouts were generated to examine vessel regeneration in mice.ResultsERG and FLI‐1 protein levels were reduced in the blood and lymphatic vasculature in SSc skin biopsy samples. ERG levels were shown to regulate genes involved in lymphatic vessel specification, including vascular endothelial growth factor receptor 3/FLT‐4, lymphatic vessel endothelial hyaluronan receptor 1, SOX‐18, and prospero homeobox 1 (PROX‐1), whereas FLI‐1 enhanced the function of ERG. The ERG–FLT‐4 pathway regulated in vitro tubulogenesis in human LECs. Deficiency of ERG or FLI‐1 similarly impaired the function of blood vessels in mice. However, only ERG deficiency affected the regeneration of lymphatic vessels during wound healing.ConclusionERG and FLI‐1 are essential regulators of blood and lymphatic vessel regeneration. Deficiency of ERG and FLI‐1 in SSc endothelial cells may contribute to the impairment of blood and lymphatic vasculature in patients with SSc.

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127

项与 VEGFR3 相关的新闻（医药）

2024-10-25

·ioncology

ILCA 2024丨元云飞教授：REFINE研究报道介入治疗亚组数据，真实世界TACE联合靶向治疗有生存获益

编者按：第18届国际肝癌协会（ILCA）年会于2024年10月17—19日在加拿大多伦多举行。本次大会上,美国加州大学洛杉矶分校（UCLA）大卫·格芬医学院的Richard S. Finn教授再次报道了真实世界REFINE研究的亚组分析，结果表明在接受瑞戈非尼治疗的不可切除肝细胞癌（uHCC）患者中，接受过经动脉化疗栓塞（TACE）和经动脉放射栓塞（TARE）的患者具有更好的生存获益趋势。《肿瘤瞭望》特邀中山大学肿瘤防治中心元云飞教授介绍和点评该研究如下。研究简介在常规临床实践中接受瑞戈非尼治疗的不可切除肝细胞癌患者的观察性研究（REFINE）：根据先前的经动脉化疗栓塞（TACE）和经动脉放射栓塞（TARE）的亚组分析背景瑞戈非尼被批准用于治疗不可切除肝细胞癌（uHCC）患者，这些患者在接受索拉非尼治疗后发生病情进展，这一批准是基于 III期RESORCE试验中总生存期（OS）改善。国际前瞻性观察性研究REFINE研究（NCT03289273）证实了瑞戈非尼在广泛uHCC患者群体中的安全性和有效性，这与RESORCE的结果一致。这项REFINE研究的亚组分析根据先前的经动脉化疗栓塞（TACE）和经动脉放射栓塞（TARE）对患者进行了评估。方法 REFINE研究包括了由医生在登记前决定使用瑞戈非尼治疗的uHCC患者，且符合当地卫生当局批准的标签。主要目标是评估安全性（根据MedDRA v25编码；根据NCI CTCAE v4.03分级）以及由于治疗紧急不良事件（TEAEs）导致的剂量调整。次要终点包括OS和治疗持续时间（DoT）。结果共有1005例患者可供评估。基线时，中位年龄为66岁，83%为男性，62%为BCLC C期，82%的ECOG PS为0或1，55%来自亚洲。大多数患者曾接受过索拉非尼治疗（96%），10%的患者曾接受过免疫检查点抑制剂。大多数患者（58%）既往接受过TACE，3%的患者接受过TARE。在接受过TACE的患者中，68%来自亚洲，而只有29%接受过TARE的患者来自亚洲。总体而言，基线特征在亚组间是一致的。接受过TACE或TARE治疗的患者的整体安全性概况与未接受过的患者相似。接受过TACE治疗的患者具有更长的中位OS（log-rank P = 0.03），中位OS（95% CI）达到了41.7个月（38.7, 45.5）。接受过TARE相关的OS益处的趋势也相似（log-rank P = 0.47），中位OS（95% CI）为35.1个月（25.7, 51.2）。结论在瑞戈非尼治疗的患者中，与没有接受过TACE的患者相比，接受过TACE治疗的患者具有OS获益。这种趋势在接受过TARE治疗的患者中也较明显，尽管分析中的患者数量很少。研究点评瑞戈非尼是一种口服的多激酶抑制剂，可阻断肿瘤生长和进展过程中的多种蛋白激酶，包括血管形成（VEGFR1—3、TIE2）、肿瘤增殖（KIT、RET、RAF-1、BRAF）、肿瘤微环境（VEGFR3、PDGFR、FGFR）以及肿瘤免疫（CSF1R）的激酶。国际多中心3期RESORCE研究[2]的阳性结果，使得瑞戈非尼成为第一个获批的uHCC二线靶向治疗药物，真实世界REFINE研究[3]进一步验证了瑞戈非尼的疗效和安全性。RESORCE研究发表至今已过去7年（Lancet,2017），在此期间，国内外进行了大量的中晚期HCC介入联合系统治疗的探索，其中TACE联合靶向治疗是较为常见的探索方案。理论上，TACE等介入治疗除了能够降低肿瘤负荷以外，还可以和靶向治疗、免疫治疗发挥协同抗肿瘤作用，主要由于这些综合治疗手段能够促进肿瘤血管正常化、改善免疫微环境和促进肿瘤抗原的释放[4-5]。因此，在TACE治疗基础上联合靶向、免疫等系统治疗，或可进一步提高疗效和增加生存获益。这次ILCA报道的REFINE研究亚组分析再次验证了这一理念，在瑞戈非尼治疗的患者中，接受过TACE或TARE的患者表现出更好的生存获益。联合治疗的耐受性是临床较为关注的问题之一，在这项研究中，总体上接受过或未接受过TACE（50% vs 58%）患者的≥3级治疗期间不良事件（TEAEs）发生率相当，表明TACE联合瑞戈非尼没有增加不良反应。当然，这是一项真实世界研究，具体的介入治疗时机、次数等情况并不清楚，但总体上患者是可以耐受的，接受过或未接受过TACE（30% vs 32%）患者的停药率相当。国内曾回顾性报道过瑞戈非尼联合TACE用于uHCC二线治疗，结果显示有较好的ORR（42.3%）和DCR（66.1%），仅有9例患者出现3/4级不良反应[6]。这些结果都验证了TACE联合瑞戈非尼用于晚期HCC治疗的可行性。随着靶向、免疫治疗的发展，近年来有了更多的TACE联合治疗探索，尤其是TACE作为中期HCC治疗标准，在此基础上联合靶向、免疫治疗已经积累了丰富的循证医学证据。例如，今年ESMO大会报道的3期LEAP-012研究[7]中，在TACE基础上联合“可乐组合”（帕博利珠单抗＋仑伐替尼）用于中期肝癌可显著改善无进展生存期（PFS：14.6 vs 10.0个月；HR 0.66，P=0.0002）；而既往报道的3期EMERALD-1研究[8]中，局晚期肝癌患者在TACE基础上联合“D+B”（度伐利尤单抗＋贝伐珠单抗），同样可以显著改善PFS（15.0 vs 8.2个月，HR 0.77，P=0.032）。综上所述，TACE等介入治疗与靶向、免疫联合治疗具有良好的协同增效机制，随着药物组合的丰富以及治疗范围的拓展，该联合治疗方案有望为HCC带来更多治疗变革，造福更多患者。参考文献上下滑动查看更多内容 [1]Richard S. Finn, et al.OBSERVATIONAL STUDY OF PATIENTS WITH UNRESECTABLE HEPATOCELLULAR CARCINOMA TREATED WITH REGORAFENIB IN ROUTINE CLINICAL PRACTICE (REFINE): SUBGROUP ANALYSIS BY PRIOR TRANSARTERIAL CHEMOEMBOLIZATION (TACE) AND TRANSARTERIAL RADIOEMBOLIZATION (TARE).ILCA 2024;P-69 [2]Bruix J, Qin S, Merle P, et al. Regorafenib for patients with hepatocellular carcinoma who progressed on sorafenib treatment (RESORCE): a randomised, double-blind, placebo-controlled, phase 3 trial [published correction appears in Lancet. 2017 Jan 7;389(10064):36. doi: 10.1016/S0140-6736(16)32615-0]. Lancet. 2017;389(10064):56-66. doi:10.1016/S0140-6736(16)32453-9 [3]Richard S. Finn,et al.Real-world dosing of regorafenib in patients with unresectable hepatocellular carcinoma (uHCC): Final analysis of the prospective, observational REFINE study. Journal of Clinical Oncology,Volume 41, Number 4_suppl. https://doi.org/10.1200/JCO.2023.41.4_suppl.518 [4]Perfahl H, Jain HV, Joshi T, et al. Hybrid Modelling of Transarterial Chemoembolisation Therapies (TACE) for Hepatocellular Carcinoma (HCC). Sci Rep. 2020;10(1):10571. Published 2020 Jun 29. doi:10.1038/s41598-020-65012-1 [5]Tachiiri T, Nishiofuku H, Maeda S, et al. Vascular Normalization Caused by Short-Term Lenvatinib Could Enhance Transarterial Chemoembolization in Hepatocellular Carcinoma. Curr Oncol. 2023;30(5):4779-4786. Published 2023 May 5. doi:10.3390/curroncol30050360 [6]Wang H, Xiao W, Han Y, et al. Study on safety and efficacy of regorafenib combined with transcatheter arterial chemoembolization in the treatment of advanced hepatocellular carcinoma after first-line targeted therapy. J Gastrointest Oncol. 2022;13(3):1248-1254. doi:10.21037/jgo-22-395 [7]Llovet JM, et al. Transarterial chemoembolization (TACE) with or without lenvatinib (len) +pembrolizumab (pembro) for intermediate-stage hepatocellular carcinoma (HCC): Phase III LEAP-012 study.2024ESMO LBA3. [8]Riccardo Lencioni,et al.EMERALD-1: A phase 3, randomized, placebo-controlled study of transarterial chemoembolization combined with durvalumab with or without bevacizumab in participants with unresectable hepatocellular carcinoma eligible for embolization.Journal of Clinical Oncology,Volume 42, Number 3_suppl.https://doi.org/10.1200/JCO.2024.42.3_suppl.LBA432 元云飞教授中山大学二级教授、二级研究员、一级主任医师、博士生导师中山大学附属肿瘤医院肝脏外科主诊教授华南恶性肿瘤防治全国重点实验室PI 专长：肝脏肿瘤的外科治疗和介入治疗中国医师协会外科医师分会肝脏外科专家工作组专家委员广东省抗癌协会肿瘤转移专业委员会主任委员广东省临床医学学会肝癌与肝转移瘤专业委员会主任委员《Cancer Communications》编委《中华普通外科学文献电子版》编委《中华肝脏外科手术学电子版》编委《岭南现代临床外科》编委（来源：《肿瘤瞭望》编辑部）声明凡署名原创的文章版权属《肿瘤瞭望》所有，欢迎分享、转载。本文仅供医疗卫生专业人士了解最新医药资讯参考使用，不代表本平台观点。该等信息不能以任何方式取代专业的医疗指导，也不应被视为诊疗建议，如果该信息被用于资讯以外的目的，本站及作者不承担相关责任。

临床结果临床3期申请上市临床研究

2024-10-14

·医药观澜

卫材口服癌症新药「仑伐替尼」新适应症在中国申报上市

10月12日，中国国家药监局药品审评中心（CDE）官网公示，卫材（Eisai）申报的甲磺酸仑伐替尼胶囊新适应症上市申请获得受理，具体适应症尚未公示。仑伐替尼为卫材公司研发的一种口服多激酶抑制剂，此前已经在全球范围内获批多项癌症适应症。公开资料显示，仑伐替尼（lenvatinib）是一种口服多种激酶抑制剂，可以选择性抑制多种激酶的活性，包括血管内皮生长因子受体（VEGFR1、VEGFR2和VEGFR3），以及成纤维细胞生长因子受体（FGFR1、FGFR2、FGFR3和FGFR4），此外还有致病性血管生成、肿瘤生长和癌症进展相关受体酪氨酸激酶，如血小板衍生生长因子受体α（PDGFRα）、KIT和RET。仑伐替尼作为单药，已经在日本、美国、欧洲、中国等国家和地区获批用于一线治疗甲状腺癌和肝细胞癌，在日本也被批准用于治疗胸腺癌。仑伐替尼与依维莫司联合疗法已经在美国、欧洲和亚洲等地被批准用于二线治疗肾细胞癌；与抗PD-1单抗帕博利珠单抗组成的联合疗法已经在多地获批用于一线治疗肾细胞癌、既往经过全身治疗的子宫内膜癌等。根据卫材官网最新管线信息，仑伐替尼还有3项国际多中心（含中国）3期临床研究正在进行中，针对适应症包括：联合经动脉化疗栓塞术（TACE）一线治疗肝细胞癌（LEAP-012研究）；联合化疗一线治疗食管癌（LEAP-014）；联合化疗一线治疗胃癌（LEAP-015）。在今年的美国临床肿瘤学会（ASCO）年会上，研究人员还公布了LEAP-012研究的研究结果，该研究旨在评估评估帕博利珠单抗+仑伐替尼联合TACE与双安慰剂+TACE治疗不可切除的非转移性肝细胞癌（HCC）患者的疗效。研究表明，在中位随访25.6个月后，帕博利珠单抗+仑伐替尼联合TACE在无进展生存方面显示出具有统计学意义和临床意义的改善，与单独使用TACE相比，将疾病进展或死亡风险降低了34%。帕博利珠单抗+仑伐替尼方案的中位无进展生存期为14.6个月，而TACE方案的中位无进展生存期为10.0个月。期待仑伐替尼后续临床研究也顺利进行，早日为更多的患者带来新的治疗选择。参考资料： [1]中国国家药监局药品审评中心（CDE）官网. Retrieved Oct 12，2024, From https://www.cde.org.cn/main/xxgk/listpage/4b5255eb0a84820cef4ca3e8b6bbe20c [2]卫材官网研发管线. Retrieved Aug 2, 2024, from https://www.eisai.com/innovation/research/pipeline/index.html [3]LEAP-012: Pembrolizumab Plus Lenvatinib Added to TACE Improved Progression-Free Survival in HCC. Retrieved Sep 16, 2024, from https://ascopost.com/news/september-2024/leap-012-pembrolizumab-plus-lenvatinib-added-to-tace-improved-progression-free-survival-in-hcc/ 内容来源于网络，如有侵权，请联系删除。

ASCO会议临床结果申请上市

2024-09-30

·正大天晴药业集团

正大天晴安罗替尼闪耀2024 CSCO，彰显抗肿瘤巨大潜力

9月29日，第27届全国临床肿瘤学大会暨2024年CSCO学术年会在厦门圆满落幕。会上，正大天晴药业集团的5项口头报告、8项壁报交流、13项摘要收录相继亮相。其中，4项口头报告展示了正大天晴抗血管生成“明星”靶向药——安罗替尼治疗肉瘤、胰腺癌、尿路上皮癌的最新研究成果，彰显了其在抗肿瘤领域的非凡潜力。安罗替尼是中正大天晴自主研发的一款口服新型小分子多靶点受体酪氨酸激酶抑制剂（TKI），能抑制VEGFR 1-3、PDGFR α/β、FGFR 1-4、c-Kit等激酶，达到抑制肿瘤血管新生、抑制肿瘤生长、调控免疫微环境的作用。目前，该产品已在国内获批6个适应症：晚期非小细胞肺癌、软组织肉瘤、三线小细胞肺癌、甲状腺髓样癌、分化型甲状腺癌、一线广泛期小细胞肺癌，并在今年7月荣获“中国新药开拓奖”。口头报告亮点骨与软组织肿瘤专场安罗替尼联合特瑞普利单抗一线治疗不可切除或转移性未分化多形性肉瘤的单臂、多中心研究初步分析研究内容：从2019年11月至2024年6月，本研究共入组17例患者接受安罗替尼联合特瑞普利单抗治疗。中位随访时间为14.9个月，主要终点3个月无进展生存率（PFR3m）为76.92%，次要终点客观缓解率（ORR）61.54%、疾病控制率（DCR）84.62%、中位总生存期（mOS）22.14个月，中位无进展生存（mPFS）7.96个月、3-4级与治疗相关的不良事件（3-4级TRAEs）发生率7.89%。研究表明，安罗替尼联合特瑞普利单抗治疗不可切除或转移性未分化多形性肉瘤可显示出抗肿瘤作用。[1] 安罗替尼对比安慰剂辅助治疗局部高级别软组织肉瘤的随机对照、双盲、Ⅱ期临床研究研究内容：从2019年6月至2023年11月，本研究入组88例高级别软组织肉瘤完全切除后未接受辅助化疗的成人患者，入组者随机分为两组接受安罗替尼或安慰剂治疗。截至2024年1月，安罗替尼组主要终点1年无病生存期（DFS）率和2年无病生存期（DFS）率分别为88%和77%，安慰剂组分别为64%和58%。研究表明，术后安罗替尼单药辅助可以降低完全切除的高级别软组织肉瘤患者的疾病复发风险。[2] 胰腺癌专场派安普利单抗和安罗替尼联合白蛋白结合型紫杉醇/吉西他滨一线治疗转移性胰腺癌—一项前瞻性、多中心、Ⅱ期临床研究研究内容：本研究共纳入66例既往未经治疗的晚期转移性胰腺癌患者，接受派安普利单抗和安罗替尼，以及白蛋白结合型紫杉醇、吉西他滨的治疗。研究显示，主要终点客观缓解率（ORR）为50.0%、疾病控制率（DCR）为95.5%，次要终点中位无进展生存期（mPFS）为8.8个月、中位总生存期（mOS）为13.7个月。此外，基线时低血清CA724水平、高T细胞募集、低Th17细胞募集和高NK CD56dim的细胞评分可以作为潜在预测性生物标志物，未来有望通过对此类生物标志物的探索实现个性化治疗和精准医疗。[3] 尿路上皮癌专场安罗替尼联合吉西他滨和顺铂或安罗替尼联合派安普利单抗围术期治疗局部晚期尿路上皮癌（ALTER-UC-007）—一项开放标签、前瞻性、Ⅱ期临床研究研究内容：本研究共入组6例膀胱癌患者，PD-L1表达阴性患者接受安罗替尼+吉西他滨+顺铂新辅助治疗4个周期后，接受根治性手术和2个周期的辅助治疗，PD-L1表达阳性患者接受安罗替尼+派安普利单新辅助治疗4个周期后，接受根治性手术和2个周期的辅助治疗。截至2024年6月3日，中位随访时间为7.8个月，主要终点客观缓解率（ORR）为50%，5例接受手术的患者病理完全缓解率（pCR）为40.0%。研究表明，安罗替尼联合吉西他滨、顺铂或安罗替尼联合派安普利单抗围手术期治疗局部晚期尿路上皮癌显示出初步疗效。[4] 今年7月，安罗替尼联合化疗一线治疗晚期软组织肉瘤的研究取得阳性成果以来，更多肉瘤领域的研究进展逐步显现。今年8月，安罗替尼联合贝莫苏拜单抗一线治疗晚期肾癌的上市申请获受理后，本次大会公布其用于尿路上皮癌的全新前瞻性研究，表明企业进一步开拓泌尿系统的肿瘤布局。此次大会，正大天晴还有1类创新药贝莫苏拜单抗、艾贝格司亭α、派安普利单抗、TQB3616和TQB2618的其他20余项研究入选。未来，正大天晴将继续秉承“健康科技，温暖更多生命”的理念，在抗肿瘤药物的研发道路上砥砺前行。参考文献： [1]Zhen Guo.CSCO 2024 [2]Chunmeng Wang.CSCO 2024 [3]Juan Du.CSCO 2024 [4]Hailiang Zhang.CSCO 2024 声明： 1. 本新闻稿旨在促进医药信息的沟通和交流，仅供医疗卫生专业人士参阅，非广告用途。 2. 本公司不对任何药品和/或适应症作推荐。 3. 本新闻稿中涉及的信息仅供参考，不能以任何方式取代专业的医疗指导，也不应被视为诊疗建议。若您想了解具体疾病诊疗信息，请遵从医生或其他医疗卫生专业人士的意见或指导。内容来源：正大天晴“晴医荟”公众号 ● 主要终点PFS双重显著获益！正大天晴乳腺癌1类新药库莫西利亮相2024 CSCO ● 展现难治性疾病治疗潜力，正大天晴BCL-2抑制剂等四项创新药研究临床数据公布 ● 中位无进展生存期18.96个月！正大天晴双国产创新药组合一线治疗晚期肾癌最新研究数据亮相2024 ESMO ● 双终点阳性！正大天晴安罗替尼联合派安普利单抗一线治疗晚期肝癌重要突破闪耀2024ESMO

CSCO会议临床结果临床2期