A Phase 1/2, Open-label, 2-arm Study Evaluating BLU-263 as Monotherapy and in Combination With Azacitidine, in Patients With KIT Altered Hematologic Malignancies

The goal of this clinical trial is to evaluate elenestinib (BLU-263) in participants with Advanced Systemic Mastocytosis (AdvSM), SM with an associated hematologic neoplasm (SM-AHN), and other hematologic malignancies. The main questions it aims to answer are:
* Determine Recommended Dose of elenestinib (BLU-263) monotherapy for participants with AdvSM
* Safety and tolerability of elenestinib (BLU-263) monotherapy
* Efficacy of elenestinib (BLU-263) monotherapy in participants with AdvSM
* Determine Recommended Dose of elenestinib (BLU-263) in combination with azacitidine in participants with AdvSM
* Safety and tolerability of elenestinib (BLU-263) in combination with azacitidine
* Efficacy of elenestinib (BLU-263) in combination with azacitidine in participants with AdvSM
The estimated study duration for each participant will be approximately 4 years: 2 years of treatment followed by 2 years of follow-up. Participants may be required to attend monthly visits for the first six months, followed by quarterly visits for the remainder of the study.

开始日期2023-09-25

申办/合作机构

Blueprint Medicines Corp.

NCT04910685

/ Recruiting临床2/3期

A Randomized, Double-Blind, Placebo-Controlled Phase 2/3 Study of BLU-263 in Indolent Systemic Mastocytosis

This is a randomized, double-blind, placebo-controlled, Phase 2/3 study comparing the efficacy and safety of elenestinib (BLU-263) + symptom directed therapy (SDT) with placebo + SDT in participants with indolent systemic mastocytosis (ISM) whose symptoms are not adequately controlled by SDT. Parts 1 and 2 will enroll participants with ISM. Participants enrolled in Part 2 will roll over onto Part 3 to receive treatment with elenestinib in an open-label fashion following completion of the earlier Part. Part K will enroll participants with ISM who have previously received an approved selective KIT inhibitor. The study also includes pharmacokinetic (PK) groups that will enroll participants with ISM.

开始日期2021-11-30

申办/合作机构

Blueprint Medicines Corp.

100 项与 Elenestinib 相关的临床结果

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100 项与 Elenestinib 相关的转化医学

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100 项与 Elenestinib 相关的专利（医药）

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项与 Elenestinib 相关的文献（医药）

2023-12-01·Expert opinion on emerging drugs

Systemic mastocytosis: 2023 update on diagnosis and management in adults.

Review

作者: Costa, Alessandro ; Masucci, Chiara ; Carmosino, Ida ; Ielo, Claudia ; Capriata, Marcello ; Scalzulli, Emilia ; Passucci, Mauro ; Martelli, Maurizio ; Breccia, Massimo

INTRODUCTION:

Systemic mastocytosis (SM) is a complex and heterogeneous disease, characterized by the clonal accumulation of mast cells in one or more organs. In 2022 both the World Health Organization (WHO) and the International Consensus Classification (ICC) modified the diagnostic and classification criteria of SM. Moreover, the identification of new clinical and molecular variables has improved prognostic tools and led to increasingly individualized therapeutic strategies.

AREAS COVERED:

The aim of this review is to present the updates introduced by the International Consensus Classification in diagnostic criteria of SM. In addition, we report the latest data available from the most important clinical trials in patients both with non-advanced and advanced disease, including elenestinib and bezuclastinib.

EXPERT OPINION:

Diagnosis and classification of SM has evolved over years. The most recent WHO and ICC classification improved SM diagnostic work-up, providing clinicians with a clear and simplified diagnostic scheme. New approved targeted therapies such as midostaurin and avapritinib modified the treatment paradigm in patients in advanced stage, and next-generation inhibitors actually investigated in clinical trials are expected in the next future.

2022-12-09·Hematology. American Society of Hematology. Education Program

Available and emerging therapies for bona fide advanced systemic mastocytosis and primary eosinophilic neoplasms

Review

作者: Gotlib, Jason

Abstract:

The historically poor prognosis of patients with advanced systemic mastocytosis (AdvSM) and primary eosinophilic neoplasms has shifted to increasingly favorable outcomes with the discovery of druggable targets. The multikinase/KIT inhibitor midostaurin and the highly selective KIT D816V inhibitor avapritinib can elicit marked improvements in measures of mast cell (MC) burden as well as reversion of MC-mediated organ damage (C-findings) and disease symptoms. With avapritinib, the achievement of molecular remission of KIT D816V and improved survival compared with historical therapy suggests a potential to affect disease natural history. BLU-263 and bezuclastinib are KIT D816V inhibitors currently being tested in trials of AdvSM. In the new World Health Organization and International Consensus Classifications, the category of “myeloid/lymphoid neoplasms with eosinophilia and tyrosine kinase (TK) gene fusions” is inclusive of rearrangements involving PDGFRA, PDGFRB, FGFR1, JAK2, FLT3, and ETV6::ABL1. While the successful outcomes with imatinib in FIP1L1::PDGFRA-positive cases and PDGFRB-rearranged neoplasms have become the “poster children” of these disorders, the responses of the other TK-driven neoplasms to small-molecule inhibitors are more variable. The selective FGFR inhibitor pemigatinib, approved in August 2022, is a promising therapy in aggressive FGFR1-driven diseases and highlights the role of such agents in bridging patients to allogeneic transplantation. This review summarizes the data for these approved and investigational agents and discusses open questions and future priorities regarding the management of these rare diseases.

Journal of Blood Medicine

Management of Advanced Systemic Mastocytosis: Clinical Challenges

Review

作者: Mascarenhas, John ; Wagner, Nicole ; Tremblay, Douglas ; Wagner, Nicole E

Advanced systemic mastocytosis (AdvSM) is a rare hematologic malignancy with organ damage and compromised life expectancy arising from organ accumulation of neoplastic mast cells. Identification of the gain-of-function KITD816V in the majority of cases has accelerated pharmaceutical development culminating with the development of selective KIT inhibitors such as avapritinib. While the advent of these therapies has improved the quality and quantity of life in patients with AdvSM, current challenges remain in the management of this disease. In this review, we summarize the present and future therapeutics landscape of AdvSM, highlighting the development of novel KIT inhibitors including elenestinib and bezuclastinib. We also explore the continued role of additional treatment modalities including allogeneic stem cell transplantation before discussing unresolved clinical challenges in the management of AdvSM.

项与 Elenestinib 相关的新闻（医药）

2025-06-03

·思齐俱乐部

90亿美元！赛诺菲斥巨资收购

当地时间6月2日，法国制药巨头赛诺菲与美国生物药企Blueprint Medicines公司宣布达成收购协议，赛诺菲将以约95亿美元的潜在总金额收购Blueprint。当天美股盘前，Blueprint股价大涨超过26%。截至当天港股收盘，Blueprint的中国合作伙伴基石药业（2616.HK）股价上涨近5%。赛诺菲方面称，此次收购不仅将为赛诺菲带来一款快速增长且唯一获批用于治疗晚期和惰性系统性肥大细胞增多症（ASM&ISM）的药物阿伐替尼（Ayvakit/Ayvakyt），还将进一步拓展其在罕见免疫疾病领域的研发管线。作为此次收购的核心资产之一，阿伐替尼是目前全球范围内唯一获批用于治疗晚期和惰性系统性肥大细胞增多症的药物。该药物是一种强效且选择性的激活KIT和PDGFRA突变激酶抑制剂，能够有效抑制导致系统性肥大细胞增多症的根本原因。这种疾病的特征是异常肥大细胞在骨髓、皮肤、胃肠道和其他器官中积聚和激活。赛诺菲财报数据显示，2024年该药物实现了4.79亿美元的净收入，并在2025年第一季度取得了近1.5亿美元的收入，同比增长超过60%。值得关注的是，阿伐替尼已在中国获批上市，并获中国首部“系统性肥大细胞增多症诊疗指南” 推荐为一线用药。赛诺菲称，在中国，阿伐替尼由基石药业销售，基石药业根据销售额支付分成百分比的特许权使用费。此次收购还将为赛诺菲带来下一代系统性肥大细胞增多症药物elenestinib，以及Blueprint研发管线内的高选择性、强效的口服野生型KIT抑制剂BLU-808，该抑制剂有望治疗多种免疫性疾病。根据伦敦证券交易所的数据，赛诺菲的这项收购也是今年至今为止欧洲药企最大规模的一笔医疗健康收购交易。近年来，赛诺菲收购动作频频。上个月，赛诺菲还宣布以4.7亿美元收购Vigil Neuroscience；去年，赛诺菲以22亿美元收购美国生物技术公司Inhibrx。赛诺菲CEO韩保罗（Paul Hudson）表示，这笔交易是对赛诺菲近期收购其他早期药物的补充。他还表示，赛诺菲仍保留相当大的进一步收购能力。来源：第一财经点击阅读原文了解更多

并购财报引进/卖出

2025-06-03

·生物制品圈

赛诺菲 95 亿美元收购 Blueprint，加码罕见病与免疫领域布局

2025 年 6 月 2 日，赛诺菲（Sanofi）宣布一项重磅交易，以 95 亿美元收购 Blueprint Medicines，旨在通过此次收购拓展其罕见病产品组合，并加强在免疫领域的早期管线布局。这一交易成为赛诺菲今年以来的第三笔收购，凸显了其在专业护理领域的战略野心。一、95 亿美元收购：锁定罕见病明星产品与潜力管线赛诺菲为此次收购支付 91 亿美元预付款，若 Blueprint Medicines 的候选药物 BLU-808 达到开发和监管里程碑，交易总价值将升至 95 亿美元。此次收购的核心资产是已获批的系统性肥大细胞增多症治疗药物 Ayvakit。Blueprint Medicines 在 2024 年凭借该产品实现 4.79 亿美元净产品收入，2025 年第一季度同比增长 61% 后，将全年指引上调至 7 亿至 7.2 亿美元。赛诺菲专业护理业务负责人布莱恩・福德（Brian Foard）在与分析师的电话会议中表示，Ayvakit 的市场推广 “刚刚起步”，赛诺菲对 Blueprint 的估值反映了该产品目前 “极低的先进疗法渗透率”，以及公司对其长期潜力的信心。Leerink 分析师安迪・贝伦斯（Andy Berens）预计，Blueprint 的收入将在 2030 年达到 17 亿美元，而市场共识预期更高，达 21 亿美元。二、管线协同：下一代疗法与免疫领域新突破除了已上市的 Ayvakit，赛诺菲还将获得 Blueprint Medicines 的下一代系统性肥大细胞增多症疗法 elenestinib。赛诺菲首席执行官保罗・哈德森（Paul Hudson）向分析师强调，elenestinib 提供了 “贯穿 2030 年代的增长机会”，其潜力 “至关重要”。另一项推动交易的关键管线是 BLU-808，这是一种 KIT 抑制剂，可应用于多种炎症性疾病。赛诺菲计划借助 BLU-808 在免疫领域的潜力，与现有管线形成协同。福德指出，Blueprint 在关键专科医生中的既有影响力与赛诺菲正在构建的免疫药物管线（如 amlitelimab、lunsekimig 和 TL1A）高度契合，其商业基础设施能自然融入赛诺菲的皮肤科、过敏科和消化科等推广渠道。三、战略布局：赛诺菲的收购狂潮与资本运作此次收购是赛诺菲今年以来的第三笔收购。此前，该公司分别以 6 亿美元和 4.7 亿美元收购了 Dren Bio 和 Vigil Neuroscience。这些交易为赛诺菲补充了管线，哈德森坦言，公司过去一年的管线 “在某些数据读出方面经历了坎坷”，而收购成为快速增强竞争力的重要手段。尽管 95 亿美元的收购规模已达哈德森此前承诺的估值上限，赛诺菲的收购 appetite 并未满足。首席财务官弗朗索瓦 - 格扎维埃・罗杰（François-Xavier Roger）表示，公司仍保留 “进行进一步业务开发的重要能力，尤其是在早期药物和疫苗领域”，将通过现金和新债务为交易融资。四、行业影响：罕见病领域整合加速赛诺菲此次收购凸显了罕见病领域的战略重要性。随着基因治疗和精准医疗的发展，罕见病药物市场正成为大型药企的必争之地。Ayvakit 在系统性肥大细胞增多症治疗中的潜力，以及 elenestinib 和 BLU-808 的后续开发，可能为赛诺菲带来数十亿美元的长期收益。然而，分析师也对 Ayvakit 的增长轨迹存在疑问，特别是其专利到期时间可能在 2034 年或 2040 年。福德仅表示公司对知识产权 “极为放心”，未作进一步评论。未来，赛诺菲需要证明其有能力扩大患者群体，并通过管线协同实现 blockbuster 级销售，以兑现此次高额收购的价值。赛诺菲在罕见病和免疫领域的持续布局，不仅将影响自身的产品组合和收入结构，也可能引发行业内更多的整合活动，推动罕见病治疗领域的创新与发展。参考来源：https://www.biospace.com/deals/sanofi-inks-9-5b-blueprint-buyout-to-expand-rare-disease-portfolio识别微信二维码，添加生物制品圈小编，符合条件者即可加入生物制品微信群！请注明：姓名+研究方向！版权声明本公众号所有转载文章系出于传递更多信息之目的，且明确注明来源和作者，不希望被转载的媒体或个人可与我们联系(cbplib@163.com)，我们将立即进行删除处理。所有文章仅代表作者观点，不代表本站立场。

并购免疫疗法疫苗引进/卖出基因疗法

2025-06-02

·药明康德

100%降解！潜在“first-in-class”口服降解剂亮眼数据公布；首次！阿斯利康小分子降解剂一线疗法3期试验结果亮眼……

首次！阿斯利康小分子降解剂一线疗法3期试验结果亮眼阿斯利康（AstraZeneca）公司日前宣布，3期临床试验SERENA-6的分析显示，其在研口服选择性雌激素受体降解剂（SERD）camizestrant与CDK4/6抑制剂（palbociclib、ribociclib或abemaciclib）联用，在无进展生存期（PFS）方面实现了高度具有统计学意义且临床意义显著的改善。根据新闻稿，camizestrant是在一线晚期乳腺癌治疗中，与广泛批准使用的CDK4/6抑制剂联合使用时，表现出持续PFS获益的首个新一代口服SERD及雌激素受体完全拮抗剂。SERENA-6试验评估了在一线治疗中，对于携带ESR1突变的激素受体（HR）阳性、HER2阴性晚期乳腺癌患者，从标准治疗方案芳香化酶抑制剂（AI）联合CDK4/6抑制剂，转换至camizestrant联合方案的疗效与安全性。研究结果显示，相较于标准治疗方案，camizestrant联合方案将疾病进展或死亡风险降低了56%（HR=0.44；95% CI：0.31–0.60；p<0.00001）。转换至camizestrant联合治疗患者的PFS为16.0个月，而对照组为9.2个月。值得一提的是，无论所用CDK4/6抑制剂类型如何，在临床相关的各个亚组中，均观察到一致的PFS获益。100%降解！潜在“first-in-class”口服降解剂亮眼数据公布Kymera Therapeutics今日公布其潜在“first-in-class”口服STAT6降解剂KT-621在1期健康受试者研究中的积极结果。数据显示，KT-621在每日一次口服给药下，于所有高于1.5 mg剂量水平中实现了超过90%的平均血液STAT6降解；在所有≥50 mg的多剂量递增（MAD）组中，更在血液与皮肤中均达成完全降解。此外，KT-621对Th2炎症相关生物标志物TARC和Eotaxin-3的中位数降低幅度分别高达37%与63%，表现优于或相当于现有获批药物。KT-621在本项试验中展现出优异的安全性，未观察到严重不良事件或与治疗相关的不良事件，整体耐受性与安慰剂无明显差异。Kymera公司指出，KT-621的临床表现已显著优于其预设的产品特征目标，进一步验证了其“生物制品口服化”开发策略的可行性。当前，KT-621正在中重度特应性皮炎（AD）患者中开展1b期BroADen试验，预计将在2025年第四季度公布数据，并计划分别于2025年第四季度与2026年第一季度启动针对AD与哮喘的两项2b期临床研究。超90亿美元！赛诺菲收购Blueprint Medicines今日，赛诺菲（Sanofi）与Blueprint Medicines宣布达成协议，赛诺菲将斥资超过90亿美元收购Blueprint公司。此次收购将使赛诺菲获得已在美国与欧盟获批用于治疗系统性肥大细胞增多症（SM）的罕见免疫疾病药物Ayvakit/Ayvakyt（avapritinib）。根据新闻稿，Ayvakit/Ayvakyt是首个获批用于治疗晚期与惰性系统性肥大细胞增多症（ASM与ISM）的药物，该病以异常肥大细胞在骨髓、皮肤、胃肠道及其他器官中的聚集和激活为特征。赛诺菲在本次交易中还将获得Blueprint Medicines处于不同阶段、具有潜力的免疫学创新药物管线。包含下一代SM治疗药物elenestinib，以及具备广泛免疫疾病治疗潜力的高选择性口服KIT抑制剂BLU-808。赛诺菲表示，Blueprint在过敏、皮肤病与免疫学领域的成熟管线，将有助于加强其不断扩展的免疫学产品组合。根据协议，赛诺菲将以91亿美元收购Blueprint Medicines，而后者将在BLU-808达到某些监管或临床里程碑时获得额外款项，总额可能高达95亿美元。百时美施贵宝与BioNTech达成研发合作BioNTech与百时美施贵宝（Bristol Myers Squibb）今日宣布达成合作协议，双方将共同在全球范围内开发并商业化BioNTech的在研双特异性抗体BNT327，用以治疗多种实体瘤类型。根据协议，双方将协作推进该候选药物的开发速度与适应症广度，涵盖单药治疗及与其他产品的联合方案，且两家公司均保留在额外适应症及自有管线联合用药中独立开发BNT327的权利。BNT327是一款靶向PD-L1与VEGF-A的下一代双特异性抗体，目前已在多个临床试验中进行评估，累计入组患者超过1000人。其中，多个具有注册潜力的全球3期临床试验正在评估其作为广泛期小细胞肺癌（ES-SCLC）与非小细胞肺癌（NSCLC）一线治疗的疗效，另一项针对三阴性乳腺癌（TNBC）的全球3期研究预计将在2025年底启动。初步数据显示，BNT327有望通过同时抑制两个关键肿瘤治疗靶点，实现协同的临床获益。参考资料：[1] Camizestrant reduced the risk of disease progression or death by 56% in patients with advanced HR-positive breast cancer with an emergent ESR1 tumour mutation in SERENA-6 Phase III trial. Retrieved June 2, 2025 from https://www.astrazeneca.com/media-centre/press-releases/2025/camizestrant-reduced-the-risk-of-disease-progression-or-death-by-56-in-patients-with-advanced-hr-positive-breast-cancer-with-an-emergent-esr1-tumour-mutation-in-serena-6-phase-iii-trial.html[2] Kymera Therapeutics Announces Positive First-in-Human Results from Phase 1 Healthy Volunteer Clinical Trial of KT-621, a First-in-Class, Oral STAT6 Degrader. Retrieved June 2, 2025 from https://investors.kymeratx.com/news-releases/news-release-details/kymera-therapeutics-announces-positive-first-human-results-phase[3] Press Release: Sanofi to acquire Blueprint Medicines, expanding portfolio in rare immunological disease and adding early-stage pipeline in immunology. Retrieved June 2, 2025 from https://www.sanofi.com/en/media-room/press-releases/2025/2025-06-02-05-00-00-3091541[4] BioNTech and Bristol Myers Squibb Announce Global Strategic Partnership to Co-Develop and Co-Commercialize Next-generation Bispecific Antibody Candidate BNT327 Broadly for Multiple Solid Tumor Types. Retrieved June 2, 2025 from https://investors.biontech.de/news-releases/news-release-details/biontech-and-bristol-myers-squibb-announce-global-strategic免责声明：本文仅作信息交流之目的，文中观点不代表药明康德立场，亦不代表药明康德支持或反对文中观点。本文也不是治疗方案推荐。如需获得治疗方案指导，请前往正规医院就诊。版权说明：欢迎个人转发至朋友圈，谢绝媒体或机构未经授权以任何形式转载至其他平台。转载授权请在「药明康德」微信公众号回复“转载”，获取转载须知。分享，点赞，在看，聚焦全球生物医药健康创新

临床3期引进/卖出临床结果临床2期临床成功

100 项与 Elenestinib 相关的药物交易

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适应症	最高研发状态	国家/地区	公司	日期
髓性系统性肥大细胞增多症	临床3期	美国	Blueprint Medicines Corp.	2021-11-30
髓性系统性肥大细胞增多症	临床3期	澳大利亚	Blueprint Medicines Corp.	2021-11-30
髓性系统性肥大细胞增多症	临床3期	奥地利	Blueprint Medicines Corp.	2021-11-30
髓性系统性肥大细胞增多症	临床3期	比利时	Blueprint Medicines Corp.	2021-11-30
髓性系统性肥大细胞增多症	临床3期	法国	Blueprint Medicines Corp.	2021-11-30
髓性系统性肥大细胞增多症	临床3期	德国	Blueprint Medicines Corp.	2021-11-30
髓性系统性肥大细胞增多症	临床3期	意大利	Blueprint Medicines Corp.	2021-11-30
髓性系统性肥大细胞增多症	临床3期	荷兰	Blueprint Medicines Corp.	2021-11-30
髓性系统性肥大细胞增多症	临床3期	挪威	Blueprint Medicines Corp.	2021-11-30
髓性系统性肥大细胞增多症	临床3期	葡萄牙	Blueprint Medicines Corp.	2021-11-30

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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


NCT04910685 (HARBOR, ASH2023)	N/A	髓性系统性肥大细胞增多症	-	Elenestinib 25 mg	鹽齋鑰餘夢製膚鹽淵廠(醖鹹鏇積顧憲觸範餘襯) = There were no treatment-related adverse events that led to drug discontinuation 蓋顧膚鑰製鹹壓構願餘 (製鏇衊衊淵選遞膚構鹽 ) 更多	-	2023-12-09
NCT04910685 (HARBOR, ASH2023)	N/A	髓性系统性肥大细胞增多症	-	Elenestinib 50 mg		-	2023-12-09
NCT04910685 (HARBOR, Corporate Publications) 人工标引	临床2/3期	系统性肥大细胞增多症	29	BLU-263	築憲壓鏇積醖選壓簾艱(簾選窪製鬱願顧鹽獵選) = Safety results indicated that eletinib was generally well tolerated, with no discontinuation due to adverse events 鏇構遞廠遞鏇製襯鑰願 (窪遞憲築選糧構獵築鏇 )	积极	2022-12-11