司美替尼(Selumetinib sulfate) - 药物靶点：MEK1 x MEK2_在研适应症：神经纤维瘤病，神经纤维瘤病1型，丛状神经纤维瘤_专利_临床

概要

基本信息

药物类型

小分子化药

别名

AZD-6244 hydrogen sulfate、KOSELUGO、Selumetinib

+ [20]

靶点

MEK1 x MEK2

作用方式

抑制剂

作用机制

MEK1抑制剂(双特异性丝裂原活化蛋白激酶激酶1抑制剂)、MEK2抑制剂(双特异性丝裂原活化蛋白激酶激酶2抑制剂)

治疗领域

肿瘤神经系统疾病遗传病与畸形+ [9]

在研适应症

神经纤维瘤病神经纤维瘤病1型丛状神经纤维瘤+ [57]

非在研适应症

急性早幼粒细胞白血病胆囊腺癌伴鳞状化生腺鳞癌+ [70]

原研机构

Array BioPharma, Inc.

在研机构

The University of Texas MD Anderson Cancer Center

National Cancer InstituteMerck Sharp & Dohme LLC

+ [10]

非在研机构

Boehringer Ingelheim GmbH

MedImmune LLC

Array BioPharma, Inc.

权益机构

Alexion Pharmaceuticals, Inc.

Merck & Co., Inc.

AstraZeneca PLC

+ [3]

最高研发阶段批准上市

首次获批日期

美国 (2020-04-10),

神经纤维瘤病1型丛状神经纤维瘤

最高研发阶段(中国)批准上市

特殊审评突破性疗法 (美国)、孤儿药 (美国)、孤儿药 (欧盟)、孤儿药 (韩国)、孤儿药 (澳大利亚)、优先审评 (中国)

登录后查看时间轴

结构/序列

分子式C17H17BrClFN4O7S

InChIKeyGRKFGZYYYYISDX-UHFFFAOYSA-N

CAS号943332-08-9

关联

132

项与司美替尼相关的临床试验

NCT05253131

/ Not yet recruiting临床2期IIT

A Phase 1/2 Trial of the MEK Inhibitor Selumetinib and Bromodomain Inhibitor With Durvalumab (MEDI4736), a PD-L1 Antibody for Sarcomas Including Malignant Peripheral Nerve Sheath Tumors (NF112)

A multi-institutional open-label phase 1/2 trial of selumetinib in combination with BI and durvalumab in refractory/unresectable sarcomas including MPNST. The phase 1 portion will be separated in two parts and will be open to all patients with refractory/relapsed sarcomas. The phase 2 portion will be for patients with refractory/unresectable NF1-associated MPNST.

开始日期2025-12-15

申办/合作机构

The University of Alabama at Birmingham

[+1]

NCT06188741

/ Not yet recruiting临床2期IIT

Phase 2 Trial of Selumetinib for the Prevention of Plexiform Neurofibroma Growth and Morbidity in Neurofibromatosis Type 1

Plexiform neurofibromas (PN) are known to cause significant morbidity in children with NF1. The recent FDA approval for selumetinib in children 2 years and older with inoperable symptomatic PN was based on the finding that selumetinib shrinks the majority of PN in children with NF1 and results in clinically meaningful benefit such as improvement in pain or range of motion. However, many morbidities, such as blindness or nerve damage, cannot be fully reversed with PN shrinkage. Therefore, there remains a critical need in this patient population to determine if young participants with PN in high-risk locations may benefit from early medical intervention prior to the development of clinical problems. This study will determine whether participants with asymptomatic PN in high-risk locations can potentially benefit from early treatment with selumetinib.

开始日期2025-09-01

申办/合作机构

The University of Alabama at Birmingham

[+1]

NCT06502171

/ Not yet recruiting临床1期IIT

A Phase 1/1b/2 Study of Cabozantinib in Combination With Selumetinib for Plexiform Neurofibroma in Adults and Adolescents With Neurofibromatosis Type 1

Based on the clinical activity of both selumetinib and cabozantinib as monotherapies in clinical trials, the demonstrated activity of these agents in reduced doses in preclinical studies, and the non-overlapping toxicity profiles, the study will assess the tolerability and efficacy of selumetinib and cabozantinib in combination in participants with NF1 ≥16 years old with progressive and/or symptomatic PN in a phase 1/1b/2 clinical trial.
Trial Design Phase 1 This will be an open label, dose escalation phase. Dose level escalation will be determined by a rolling six design. In this design, up to 6 participants can be enrolled at a given dose level and then evaluated for dose limiting toxicity (DLT) within the DLT window. The DLT window is defined as 16 weeks in this study based on the long half-life of cabozantinib and the desire to have maximum confidence about long-term tolerability of the combination prior to proceeding to the next dose level.
Phase 1b Once the recommended phase 2 dose has been determined in phase 1, an expanded cohort of 12 participants will be enrolled in phase 1b portion of the study.
Phase 2 This will be an open label, single-arm phase using the recommended phase 2 dose.

开始日期2025-07-01

申办/合作机构

The University of Alabama at Birmingham

[+2]

100 项与司美替尼相关的临床结果

登录后查看更多信息

100 项与司美替尼相关的转化医学

登录后查看更多信息

100 项与司美替尼相关的专利（医药）

登录后查看更多信息

1,747

项与司美替尼相关的文献（医药）

2025-12-01·CHILDS NERVOUS SYSTEM

The state of targeted therapeutic pharmacological approaches in pediatric neurosurgery: report from the European Society for Pediatric Neurosurgery (ESPN) Consensus Conference 2024

Review

作者: Due-Tønnessen, B J ; Leblond, P ; Thompson, D ; Obersnel, M ; Thomale, U W ; Di Rocco, F ; Romano, A ; Knerlich-Lukoschus, F ; Frassanito, P

Abstract:

Objective:

The development of novel targeted therapies is opening new perspectives in the treatment of pediatric brain tumors. Their precise role in therapeutic protocols still needs still to be defined. Thus, these novel pharmacological approaches in pediatric neurosurgery were the topic of the European Society for Pediatric Neurosurgery (ESPN) Consensus Conference held in Lyon (France) in January 25–27, 2024.

Method:

The paper reviews the current knowledge about targeted therapy as well as the current literature published on the topic. The conference aimed for an interdisciplinary consensus debate among pediatric oncologists and pediatric neurosurgeons on the following questions.Question 1: What is the current role for targeted therapies as neoadjuvant treatments before pediatric brain tumor removal?Question 2: What are the benefits, cost/efficiency, and long-term side effects of targeted therapies in the treatment of pediatric brain tumors?Question 3: Based on contemporary data, at which stage and in which pathologies do targeted therapies play a significant role?

Results:

Ninety-two participants answered consensus polls on the state of the art of targeted therapies, the ethical issues related to their use, and the evolving change in the role of pediatric neurosurgeons. The neoadjuvant role of targeted therapies is difficult to define as there are many different entities to consider. Despite the recently reported potential benefits, questions regarding the use of targeted therapies are manifold, in particular regarding sustainable benefits and long-term side effects. Additionally, challenging cost issues is a limiting factor for the broader availability of these drugs. Studies have demonstrated superiority of targeted therapy compared to chemotherapy both in randomized trials and compared to historical cohorts in the management of a subset of low-grade gliomas. The same drug combinations, BRAFi and MEKi, may be effective in HGG that have relapsed, progressed, or failed to respond to first-line therapy. Similar conclusions on efficacy may be drawn for mTORi in TSC and selumetinib in plexiform neurofibromas. For other tumors, the picture is still obscure due to the lack of data or even the lack of suitable targets. In conclusion, targeted treatment may not always be the best option even when a target has been identified. Safe surgery remains to be a favorable option in the majority of cases.

Conclusion:

The constantly evolving drug technology and the absence of long-term safety and efficacy studies made it difficult to reach a consensus on the predefined questions. However, a report of the conference is summarizing the present debate and it might serve as a guideline for future perspectives and ongoing research.

2025-12-01·CHILDS NERVOUS SYSTEM

Severe cervical kyphosis in a complex child with NF1, case report and literature review

Review

作者: Piatelli, Gianluca ; Santoro, Claudia ; Pola, Enrico ; De Prisco, Ferruccio ; Miele, Giuseppina ; Perrotta, Silverio ; Nasto, Luigi Aurelio

Abstract:

Purpose:

We faced and herein report a detailed description of pre-operative assessment, management, and post-operative follow-up of a 2-year and 10-month-old girl with neurofibromatosis 1 (NF1) who presented with severe, dystrophic, cervical kyphosis (170 degrees) associated with extensive pre- and para-vertebral plexiform neurofibromas, who also went under MEK inhibitors therapy. Cervical kyphosis in NF1 is particularly rare, and there is no extensive literature available on the subject in terms of clinico-radiological features, surgical approach, and outcomes. We therefore also performed a comprehensive review of the available literature on the topic.

Methods:

The clinical report was made through the retrospective review of all medical documents and imaging of the patient. The systematic review was performed based on the inclusion and exclusion criteria set by the authors on surgical management of cervical kyphosis in NF1 patients according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA).

Results:

Our patient underwent a first-stage halo-gravity traction followed by a single-stage occipito-cervical posterior fusion. The six-week traction resulted in a reduction of the deformity from 170 to 90°. A further amelioration was obtained by surgery with a final 60% correction of the curvature (69° at last post-operative X-ray). No complications were observed at 1-and-a-half-year follow-up. The plexiform neurofibromas were treated with MEK inhibitors: trametinib for 1 year and 11 months until performing halo traction, and with selumetinib after surgery. We just found 19 papers suitable according to our selection criteria.

Conclusion:

Combined anterior and posterior fusion (CAP) is generally the best treatment option, although it is not always feasible. When plexiform, symptomatic, inoperable neurofibromas coexist, surgery can be preceded or followed by MEK inhibitor treatment for better control or a volumetric reduction of the tumors. The best therapeutic choice should always be the result of a multidisciplinary, expert approach and patient-tailored design.

2025-08-01·GENE

Exploring the functional and prognostic roles of EPHX4 in pancreatic cancer: Insights from bioinformatics and experimental validation

Article

作者: Gu, Dandan ; Xiong, Wei ; Huang, Shaoyang

BACKGROUND:

Epoxide hydrolase-4 (EPHX4) belongs to the epoxide hydrolase enzyme family, but its biological function remains unclear, especially its potential involvement in the development of pancreatic tumours. This research sought to examine the function of EPHX4 in pancreatic adenocarcinoma (PAAD).

METHODS:

The expression of EPHX4 across cancers was examined through The Cancer Genome Atlas (TCGA). Bioinformatics was employed, leveraging multiple databases to investigate EPHX4 gene expression in pancreatic cancer and its association with survival prognosis, functional enrichment, immune infiltration, tumour mutation load, and drug sensitivity, among other variables. To evaluate EPHX4 expression in PAAD cells, Western blotting and reverse transcription quantitative PCR were used. A series of in vitro functional experiments was performed to assess the proliferation, migration, and invasion of PAAD cells.

RESULTS:

EPHX4 expression was markedly elevated in a number of malignancies, including PAAD, and was associated with patient sex, clinical stage, and metastasis to the lymph nodes. High EPHX4 expression was significantly associated with a worse outcome in PAAD patients. According to functional and enrichment studies, EPHX4 is involved in many signalling pathways linked to cancer. The study of immune infiltration revealed that EPHX4 was connected to the existence of a variety of immune cells inside the tumour. Our study revealed that EPHX4 knockdown significantly decreased PAAD cell migration, proliferation, and invasion.

CONCLUSION:

EPHX4 is highly expressed in PAAD and independently predicts poor survival. Functional experiments demonstrate its tumor-promoting effects. Its involvement in multiple cancer-related signaling pathways and immune regulation mechanisms highlights the dual prognostic and therapeutic potential of EPHX4 in PAAD.

192

项与司美替尼相关的新闻（医药）

2025-06-12

·漫游药化

学懂通路第三期： MAPK信号通路

导读前两期，我们讲到了受体酪氨酸激酶 RTKs（学懂通路第一期、第二期）。RTKs既是承接胞外信号的细胞膜受体，也是将信号传递至细胞内的“中转站”。本期我们将打开细胞的大门，走进细胞，学习一种重要的细胞内信号传递通路，感受信号通路从胞外进入胞内，直到进入核内并调控基因的表达、诱导特定生理效应产生的神奇过程。01前言促分裂素原活化蛋白激酶(mitogen-activated protein kinases, MAPK)信号通路是真核生物信号传递网络中的重要途径之一，是细胞增殖、分化、细胞凋亡以及正常条件和病理条件下应激反应的关键信号通路。MAPK 是一组进化保守的丝氨酸-苏氨酸激酶，可分为4个亚族：ERK、p38、JNK和BMK1（也称：ERK5），分别代表四条经典的MAPK通路。MAPK信号通路是一个级联磷酸化的过程，核心成员包括：MAP kinase kinase kinase ( MAPKKK或MKKK)、MAP kinase kinase (MAPKK或MKK)和MAP Kinase（MAPK）。目前，已经分别有25、7、13种MAPKKK、MAPKK、MAPK被鉴定出。其中，以RAF为代表的MAPKKK，作用于以MEK为代表的MAPKK，使之磷酸化并活化，活化的MEK再作用于MAPK家族信号分子，使之磷化并活化，活化的MAPK进入细胞核内调节转录调控。图 1. MAPK的四条经典通路02RAS-Raf-MEK 1/2-ERK 1/2 通路1.1 信号传递过程目前，MAPK家族中研究最为广泛的是ERK1/ERK2激酶。该通路的具体过程是：胞外的生长因子如EGF，激活酪氨酸激酶受体（如EGFR），提供接头蛋白GRB2的结合位点，招募SOS蛋白到细胞膜上。SOS通过消耗GTP活化Ras形成Ras-GTP。图 2. Ras的下游蛋白如上图所示，Ras活化后可以与下游多个蛋白产生效应，包括：AF6、PI3K、PLCε、RAF等。其中，Ras-GTP通过将Raf蛋白招募到质膜上后，使其被其他多种激酶(PKA、PAK、SRC)磷酸化，激活其激酶功能。Raf蛋白家族包含BRAF、ARAF和CRAF（Raf1），BRAF在恶性肿瘤形成、发展过程中发挥重要作用。活化的Raf激酶再进一步与下游的MEK 1/2结合并使ERK1/2激活。激活的ERK1/2 能够继续磷酸化ELK1, ETS, FOS, JUN, MYC 和SP1等转录因子，诱导与细胞周期与细胞增殖有关的基因表达；此外，激活的ERK1/2 也可以磷酸化多种细胞内的激酶，例如：RAKs、MSKs、MNKs，这些激酶对细胞的增殖和粘附产生作用。1.2 信号通路与肿瘤下图是不同实体瘤中发现的与RTK/RAS/RAF 通路相关的突变，这条信号通路与多个癌种的发生密切相关，针对这条通路上的关键靶点，已成功上市多个药物。图 3. 实体瘤中与Ras-Raf-MEK通路有关的突变1.2.1 Ras与肿瘤Ras是一种GTP结合蛋白，主要包括：H-Ras/K-Ras/N-Ras，三者相互间具有85％的氨基酸同源序列，是癌症研究的重要靶标。其中， Kras是Ras家族中最常出现的亚型，占Ras基因突变总数的85%。研究发现，Kras在90 % 胰腺导管癌中均发现突变；此外，在黑色素瘤中，Ras突变近于28％左右，其中N-Ras为主要突变体（93％）。虽然Ras与肿瘤的发生发展密切相关，但是目前仍未有直接针对Ras的靶向药物上市。最主要一个原因在于Ras蛋白的无特征、近乎球形的结构，无明显结合位点，因此在很长一段时间都被当做“不可成药靶点”。但是近年来，针对共价抑制剂研究和靶向降解剂的出现使得靶向KRAS突变体成为可能。图 4. 针对该通路各个环节开发靶向药物1.2.2 BRAF与肿瘤 RAF基因家族包含BRAF、ARAF和CRAF，其中，BRAF在恶性肿瘤形成、发展过程中发挥重要作用。BRAF最常见突变形式为第15外显子的第1,799位核苷酸上T突变为A，导致其编码的缬氨酸变为谷氨酸，即BRAF V600E突变（占BRAF所有突变的80 %）。这一突变使BRAF蛋白持续激活，活性提高约500倍，并且能够不依赖于上游RAS激酶单体，持续激活下游的ERK，最终导致细胞的无限增殖和分裂。目前针对BRAF单靶点/多靶点的药物主要有：达拉非尼、瑞戈非尼、维罗非尼、索拉非尼等。1.2.3 MEK与肿瘤MEK1/2作为易突变的蛋白Ras、Raf下游蛋白，因此也可以作为一个靶点。目前，该靶点获批的抑制剂主要用于黑色素瘤以及肺腺癌，如曲美替尼（trametinib）、司美替尼（selumetinib）等。1.2.4 ERK与肿瘤 ERK激酶是MEK激酶的唯一下游靶点，研究显示，靶向于ERK靶点的抑制剂能够有效阻断RAS-RAF-MEK-ERK信号通路，同时能够有效逆转由上游BRAF、MEK突变而导致的耐药。目前ERK抑制剂处于临床试验的主要有：AZD0364、KO-947、Ulixertinib。值得注意的是，由上海海和药物与中国科学院上海药物研究所合作开发的小分子抑制剂HH2710也已于2019年9月获美国FDA的临床试验许可，拟用于治疗经检测确认存在MAPK信号通路基因异常的恶性肿瘤。03其他三种MAPK通路图 5. ERK 1/2 和其他三种MAPK通路除了大家熟知的的Ras-Raf-MEK-ERK通路，根据MAPK的种类不同（p38、JNK、ERK5），MAPK还有三条经典的通路。其中，p38和JNK通路涉及的生理效应主要与炎症和细胞凋亡等应激反应有关。2.1 JNK/SAPK级联反应 JNK（JUN N -terminal kinases, JNK）主要包括JNK1/2/3，也称作SAPKs（stress-activated protein kinases）。JNK/SAPK信号通路可被应激刺激(如紫外线、热休克、高渗刺激及蛋白合成抑制剂等)、细胞因子(TNFα，IL-1)、生长因子(EGF)及某些G蛋白偶联的受体激活。应激反应信号经小分子G蛋白Ras超家族的成员之一Rho 亚家族（Rac、Rho、cdc42）传递到MAPKKK，进一步地依次活化MEK4/7和JNK。JNK磷酸化激活后可以作用下游多种转录因子（例如：JUN、ELK1、ETS2等）与激酶（主要是MNK），产生促进生长、分化、存活、凋亡等多种生理效应。图 6. JNK/SAPK级联反应2.2 p38级联反应P38激酶主要有四种：p38 α, β, γ 和δ，诱导该通路的主要诱因有：缺氧，紫外线辐射，渗透性休克，炎症等应激反应。P38 MAPK激酶主要由ERK3/6磷酸化激活，进一步地通过诱导转录因子及激酶促进细胞凋亡，抑制细胞增殖。此外，该通路对细胞运动也有促进作用。2.3 BMK1 （ERK5）级联反应ERK5可以被上游的MEK5激活。与ERK1/2通路类似，该通路也与细胞增殖有关。参考文献：[1] Robert, Jacques. Textbook of Cell Signalling in Cancer [M]. Springer International Publishing, 2015.[2] Wagener C , Stocking C , O. Müller. Cancer Signaling - From Molecular Biology to Targeted Therapy[M]. 2017.[3] Amanda H . Cancer cell signalling[M]. Wiley Blackwell, 2014.[4] Comprehensive pancancer genomic analysis reveals (RTK)-RAS-RAF-MEK as a key dysregulated pathway in cancer: Its clinical implications. https://doi-org.libproxy1.nus.edu.sg/10.1016/j.semcancer.2017.11.016.部分素材来源于互联网，只为知识传播，不做商业用途，侵删。预告第二期：PI3K通路；第三期：细胞因子通路；做号不易，感恩“分享”

临床2期临床1期临床终止

2025-05-30

·摩熵医药

5款MEK抑制剂上市，复星医药、百济领衔，20+在路上

注：本文不构成任何投资意见和建议，以官方/公司公告为准；本文仅作医疗健康相关药物介绍，非治疗方案推荐（若涉及），不代表平台立场。任何文章转载需要得到授权。5月29日，复星医药的1类创新药芦沃美替尼（FCN-159，商品名：复迈宁）获批上市，适用于朗格汉斯细胞组织细胞增生症（LCH）和组织细胞肿瘤成人患者；2岁及2岁以上伴有症状、无法手术的丛状神经纤维瘤（PN）的I型神经纤维瘤病（NF1）儿童及青少年患者。芦沃美替尼基本信息图片来源：摩熵医药全球药物研发数据库说到I型神经纤维瘤病（NF1），这是一种较为常见的常染色体显性遗传性疾病。在神经纤维瘤病的三种主要临床类型中，它占据了96%的比例，且已被纳入国家罕见病目录，全球发病率为1/2500-1/3000。大约30%-50%的NF1患者会出现丛状神经纤维瘤（PN），这种瘤体沿神经长轴呈弥漫性生长，常累及多条神经干、分支及神经丛，并侵及周围组织，从而引发毁容、疼痛、运动及呼吸功能障碍、视力受损以及膀胱或肠道功能障碍等一系列严重问题。鉴于NF1相关PN瘤体复杂的生长特性和侵入性生长方式，手术治疗面临着诸多挑战。瘤体往往生长于头部、颈部、脊椎等特殊部位，致使手术风险巨大、难度极高，部分瘤体无法被完全切除，且复发率居高不下，这使得手术治疗效果极为有限，因此，研发有效的治疗药物迫在眉睫。FCN-159作为复星医药开发的高活性、高选择性MEK1/2抑制剂，其作用机制至关重要。MEK是细胞外信号相关激酶（ERK）通路的上游调节因子，通过抑制MEK的活性，能够有效抑制RAS调节RAF/MEK/ERK通路的活性，进而抑制肿瘤生长。而在NF1中，RAS-丝裂原活化蛋白激酶（RAS-MAPK）通路常常发生异常，这种异常会促使细胞增殖和肿瘤沿神经生长，因此，MEK被认为是F1相关PN药物开发的潜力靶点。MEK 抑制剂的应用不仅局限于治疗NF1相关 PN，它还在黑色素瘤、结直肠癌、淋巴瘤等肿瘤的治疗领域展现出巨大潜力。据摩熵医药数据库显示，目前国内已批准5款MEK抑制剂，除了芦沃美替尼，还有诺华/百济神州的Trametinib（曲美替尼）、阿斯利康/默克的Selumetinib（氢司美替尼）、泽璟生物的Donafenibtosylate（甲苯磺酸多纳非尼）和科州制药的Tunlametinib（妥拉美替尼）。国内获批上市的MEK抑制剂图片来源：摩熵医药全球药物研发数据库此外，国内还有20余款MEK抑制剂正处于研发阶段，如卫材的E-6201（II期临床）、恒瑞医药的SHR7390（I期临床）、基石药业的CS3006（I期临床）、正大天晴的TQ-B3234（I期临床）、来凯医药的GSK-795（I期临床）、璧辰医药的ABM-168（I期临床）等。此次11款创新药集中获批，既是中国药审改革成果的集中体现，也标志着本土药企在肿瘤、罕见病等高壁垒领域实现技术突破。随着政策支持力度加大和研发体系完善，未来将有更多创新药进入临床，为患者带来生命希望。END本文为原创文章，转载请留言获取授权近期热门资源获取数据透视：中药创新药、经典验方、改良型新药、同名同方的申报、获批、销售情况-2025042023H2-2024H1中国药品分析报告-2025042024年中国1类新药靶点白皮书-202503中国AI医疗健康企业创新发展百强榜单-202502解码护肤抗衰：消费偏好洞察与市场格局分析-2025022024年FDA批准上市的新药分析报告-2025012024年NMPA批准上市的新药分析报告-2025012024年医保谈判及市场分析报告-2025.012024年中国医疗健康投融资全景洞察报告-202501小分子化药白皮书（上）-2025012024医美注射材料市场发展分析报告-202412中国放射性药物产业白皮书-202410近期更多摩熵咨询热门报告，识别下方二维码领取联系我们，体验摩熵医药更多专业服务会议合作园区服务数据库咨询定制服务媒体合作点击上方图片，即可开启摩熵化学数据查询点击阅读原文，申请摩熵医药企业版免费试用！

上市批准临床2期临床1期申请上市

2025-05-29

·医药魔方Info

复星医药MEK1/2抑制剂「芦沃美替尼」获批上市

5月29日，国家药监局网站显示，复星医药自主研发的芦沃美替尼（曾用名：复迈替尼，研发代号：FCN-159）获批上市，用于治疗朗格汉斯细胞组织细胞增生症（LCH）和组织细胞肿瘤成人患者；2岁及2岁以上伴有症状、无法手术的丛状神经纤维瘤（PN）的I型神经纤维瘤病（NF1）儿童及青少年患者。芦沃美替尼是复星医药自主研发的创新型小分子MEK1/2选择性抑制剂，目前正在开展治疗NF1成人患者的III期临床试验。针对组织细胞肿瘤的II期研究结果显示，初治或复发/难治性、不限制基因突变类型的组织细胞肿瘤患者接受芦沃美替尼（8mg）治疗后，独立评审委员会（IRC）和研究者评估的确认的客观缓解率（cORR）分别为82.8%（24/29，其中14例CMR、10例PMR）和75.9%（22/29，其中12例CMR、10例PMR），中位至缓解时间均为2.9个月。在这29例患者中，共有13例患者进行了基线cfDNA基因突变检测（其中10例BRAFmut，3例MAP2K1mut），在2次肿瘤评估后，92.3%的患者的基因突变频率降低（69.2%，9/13）或未检测到（23.1%，3/13），该检测结果与临床反应（ORR）一致。针对神经纤维瘤的II期研究结果显示，NF1儿童患者接受芦沃美替尼（5mg/2）治疗后，盲法独立审查委员会（BIRC）和研究者评估的ORR分别为44.2%和60.5%。中位缓解持续时间（DOR）和中位无进展生存期（PFS）仍未达到。研究者评估的1年 PFS 率为95.3%。根据医药魔方NextPharma数据库，目前全球范围内已获批上市的MEK1/2选择性抑制剂共7款，包括曲美替尼（诺华）、比美替尼（辉瑞）、司美替尼（阿斯利康）、考比替尼（罗氏）、妥拉美替尼（科州制药）、mirdametinib（默克）和芦沃美替尼（复星医药）。Copyright © 2025 PHARMCUBE. All Rights Reserved.欢迎转发分享及合理引用，引用时请在显要位置标明文章来源；如需转载，请给微信公众号后台留言或发送消息，并注明公众号名称及ID。免责申明：本微信文章中的信息仅供一般参考之用，不可直接作为决策内容，医药魔方不对任何主体因使用本文内容而导致的任何损失承担责任。

上市批准临床结果临床2期临床3期

100 项与司美替尼相关的药物交易

登录后查看更多信息

外链

KEGG	Wiki	ATC	Drug Bank
-	司美替尼	L01XE	DB11689

研发状态

批准上市

10 条最早获批的记录,

登录

后查看更多信息

适应症	国家/地区	公司	日期
神经纤维瘤病	韩国	AstraZeneca PLC	2021-05-28
神经纤维瘤病1型	美国	AstraZeneca Pharmaceuticals LP	2020-04-10
丛状神经纤维瘤	美国	AstraZeneca Pharmaceuticals LP	2020-04-10

未上市

10 条进展最快的记录,

登录

后查看更多信息

适应症	最高研发状态	国家/地区	公司	日期
NF1突变型丛状神经纤维瘤	申请上市	中国	AstraZeneca UK Ltd.	2025-02-20
复发性胶质母细胞瘤	临床3期	美国	National Cancer Institute	2021-02-16
复发性胶质母细胞瘤	临床3期	加拿大	National Cancer Institute	2021-02-16
复发性低级别星形细胞瘤	临床3期	美国	National Cancer Institute	2021-02-16
复发性低级别星形细胞瘤	临床3期	加拿大	National Cancer Institute	2021-02-16
复发性 WHO II 级胶质瘤	临床3期	美国	National Cancer Institute	2021-02-16
复发性 WHO II 级胶质瘤	临床3期	加拿大	National Cancer Institute	2021-02-16
结节性硬化症	临床3期	美国	National Cancer Institute	2021-02-16
结节性硬化症	临床3期	加拿大	National Cancer Institute	2021-02-16
低级别星形细胞瘤	临床3期	美国	National Cancer Institute	2020-01-31

登录后查看更多信息

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


NCT04924608 (KOMET, Pubmed \| Lancet)	临床3期	神经纤维瘤病1型 \| 丛状神经纤维瘤	184	Selumetinib 25 mg/m^2	醖襯衊遞簾網醖鑰觸繭(鏇選鏇遞積鹹鑰廠鹹餘) = 壓糧顧蓋構範廠鏇鬱範構願範構願網構窪範壓 (製範鹽廠壓觸獵範鬱構, 11.2 ~ 30.9)	积极	2025-06-01
				Placebo	醖襯衊遞簾網醖鑰觸繭(鏇選鏇遞積鹹鑰廠鹹餘) = 選壓獵築網鑰選遞範窪構願範構願網構窪範壓 (製範鹽廠壓觸獵範鬱構, 1.5 ~ 13.3)
NCT04924608 (KOMET, ASCO2025)	临床3期	NF1突变型丛状神经纤维瘤	145	Selumetinib 25 mg/m2 BID	遞顧遞製願窪範鹹鹹艱(遞選蓋夢夢願齋製鏇鹹) = 鏇鬱鏇艱鑰膚顧鑰壓鏇觸壓觸襯遞鹽鹽襯膚選 (顧顧蓋夢齋淵構鏇淵繭, 11.2 ~ 30.9)	积极	2025-05-30
				Placebo	遞顧遞製願窪範鹹鹹艱(遞選蓋夢夢願齋製鏇鹹) = 醖觸範遞鏇醖淵遞願憲觸壓觸襯遞鹽鹽襯膚選 (顧顧蓋夢齋淵構鏇淵繭, 1.5 ~ 13.3)
NCT02407405 (Pubmed \| Nat Med)	临床2期	神经纤维瘤病1型 \| 丛状神经纤维瘤	33	Selumetinib	範壓築選選鑰餘遞繭築(艱襯淵繭遞遞鑰襯遞鏇) = acneiform rash was the most prevalent AE 蓋衊艱窪網艱壓淵蓋積 (構顧繭網齋襯鬱憲餘積 )	积极	2025-01-01
NCT04924608 (KOMET, Company_Website) 人工标引	临床3期	神经纤维瘤病1型	145	selumetinib	鏇觸夢鏇鹽願積簾構廠(餘鏇糧顧鏇蓋範範簾艱) = Topline results showed that KOSELUGO, an oral, selective MEK inhibitor, demonstrated a statistically significant and clinically meaningful improvement in objective response rate (ORR), the study’s primary endpoint, versus placebo, in these adult patients. 糧鹹鑰繭簾衊壓壓窪憲 (製廠觸築築廠範餘構膚 ) 达到	积极	2024-11-12
NCT03833427 (MK-5618-001, CTgov)	临床1期	实体瘤	32	Selumetinib+Pembrolizumab (Selumetinib 50mg + Pembrolizumab)	遞獵襯簾製選鬱鏇築廠 = 簾製築窪廠鑰夢餘襯繭憲鏇糧糧膚網憲襯顧膚 (簾範構餘鹹構顧顧夢憲, 築衊衊艱選鏇獵艱鬱鏇 ~ 鹽淵觸鑰簾糧襯製觸襯) 更多	-	2024-10-30
				Selumetinib+Pembrolizumab (Selumetinib 75mg + Pembrolizumab)	遞獵襯簾製選鬱鏇築廠 = 觸窪鏇壓窪夢鏇範積醖憲鏇糧糧膚網憲襯顧膚 (簾範構餘鹹構顧顧夢憲, 獵鹽醖窪窪糧齋糧繭積 ~ 繭壓齋艱鏇鹽積艱艱獵) 更多
NCT01256359 (DOC-MEK, CTgov)	临床2期	黑色素瘤 \| 不可切除的黑色素瘤	83	AZD6244+Docetaxel (Docetaxel and AZD6244)	襯廠鬱衊衊齋鏇製範壓(遞顧廠窪願簾構艱顧齋) = 製繭餘膚鑰膚膚憲憲願餘淵鹽衊範積鏇衊鏇鏇 (遞選艱鹽簾齋網淵餘憲, 簾齋鑰願鬱築壓選鏇糧 ~ 夢構繭觸壓選選膚積淵) 更多	-	2024-08-15
				Docetaxel and placebo (Docetaxel and Placebo)	襯廠鬱衊衊齋鏇製範壓(遞顧廠窪願簾構艱顧齋) = 繭夢糧網鏇夢製積網繭餘淵鹽衊範積鏇衊鏇鏇 (遞選艱鹽簾齋網淵餘憲, 鑰鹽顧廠餘襯製願齋膚 ~ 窪簾餘積糧憲憲觸簾積) 更多
NCT02839720 (Pubmed)	临床2期	神经纤维瘤	4	Selumetinib	積廠壓鹽選遞遞艱鏇壓(選廠鹽遞鏇積網鹽顧簾) = 淵鏇窪繭範膚繭窪蓋餘觸夢範遞糧廠糧糧鹹廠 (衊範窪膚艱觸廠壓顧廠 )	-	2024-06-21
				Placebo	積廠壓鹽選遞遞艱鏇壓(選廠鹽遞鏇積網鹽顧簾) = 夢構築遞築艱窪餘選廠觸夢範遞糧廠糧糧鹹廠 (衊範窪膚艱觸廠壓顧廠 )
NCT01362803 (SPRINT, Pubmed \| Future Oncol)	临床1/2期	神经纤维瘤病1型 \| 丛状神经纤维瘤	50	Selumetinib	衊醖膚艱願願構構鹹醖(顧顧醖膚範願衊淵壓繭) = mainly mild and could be managed by doctors 簾襯窪艱壓壓齋膚糧艱 (蓋網獵簾糧選範製餘糧 ) 更多	积极	2024-05-01
AAN2024	N/A	神经纤维瘤病1型	-	Selumetinib 20mg/10mg	構鬱艱選遞願鹹醖壓築(鬱選窪遞蓋壓選選艱構) = 鑰鹽獵鹽夢夢壓憲艱鑰鑰繭築夢糧夢鑰壓蓋遞 (顧艱艱夢夢鑰窪獵網鏇 )	-	2024-04-09
				Selumetinib 20mg b.i.d.	構鬱艱選遞願鹹醖壓築(鬱選窪遞蓋壓選選艱構) = 選顧鬱廠窪選壓艱構顧鑰繭築夢糧夢鑰壓蓋遞 (顧艱艱夢夢鑰窪獵網鏇 )
NCT03833427 (Pubmed) 人工标引	临床1期	实体瘤 PDCD1 Positive	32	selumetinib 50mgselumetinib 50mg + pembrolizumabpembrolizumab 200 mg	艱艱製願構蓋憲壓醖鹽(製選夢糧艱夢鑰醖鑰艱) = 2/11 patients (18.2%) experienced DLTs (n = 1 grade 3 diarrhea, n = 1 grade 3 fatigue). In the selumetinib 125 mg group, 3/14 (21.4%) experienced DLTs (n = 1 grade 2 retinal detachment, n = 1 grade 3 retinopathy, n = 1 grade 3 stomatitis) 糧遞蓋夢餘淵鑰餘鹽獵 (醖築齋願襯鹹選廠願鏇 ) 更多	不佳	2024-03-14
				pembrolizumabpembrolizumab 200 mg + selumetinib 75mgselumetinib 75mg