A Double-blind, Phase I/II, Randomised Study to Compare the Efficacy of Enzomenib Versus Placebo as Maintenance after Allogeneic Haematopoietic Stem Cell Transplantation in Subjects with Acute Myeloid Leukaemia (AML).

开始日期2026-07-01

申办/合作机构

Australasian Leukaemia & Lymphoma Group

NCT07444268

/ Recruiting临床1期

A Phase 1, Open-label Study of the Absorption, Metabolism, and Excretion of DSP-5336 Following a Single Oral Dose in Patients With Refractory or Relapsed Acute Leukemia, Myelodysplastic Syndrome, Multiple Myeloma, or Myeloproliferative Neoplasms

The purpose of this study is to evaluate the absorption, metabolism, and excretion of DSP-5336 following a single oral administration of the study drug in patients with hematologic malignancies whose disease has progressed after available standard therapies.

开始日期2026-03-26

申办/合作机构

Sumitomo Pharma America, Inc.

NCT04988555

/ Recruiting临床1/2期

A Phase 1/2, Open-Label, Dose-Escalation, Dose-Expansion Study of Enzomenib (DSP-5336) in Patients With Acute Leukemia and Other Selected Hematologic Malignancies, With and Without Mixed Lineage Leukemia (MLL) Rearrangement or Nucleophosmin 1 (NPM1) Mutation (Horizen-1)

A phase 1/2 dose escalation / dose expansion study of Enzomenib (DSP-5336) in patients with acute leukemia.

开始日期2022-02-28

申办/合作机构

Sumitomo Pharma America, Inc.

100 项与 Enzomenib 相关的临床结果

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100 项与 Enzomenib 相关的转化医学

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100 项与 Enzomenib 相关的专利（医药）

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项与 Enzomenib 相关的文献（医药）

2025-12-05·Hematology-American Society of Hematology Education Program

The promise of menin inhibitors: from approval to triplet regimens

Review

作者: Thakur, Rahul K. ; Wang, Eunice S.

Abstract:

Pharmacologic targeting of the menin-KMT2A protein–protein interaction has emerged as a therapeutic breakthrough for acute leukemias harboring KMT2A rearrangements or NPM1 mutations. The first-in-class menin inhibitor (revumenib) achieved accelerated regulatory approval in November 2024 for monotherapy of relapsed/refractory KMT2A rearranged leukemia. Next-generation agents (ziftomenib, bleximenib, enzomenib, BMF-219) have displayed similar composite complete remission rates (20-35%) and overall response rates (45-65%) in heavily pretreated KMT2Ar and NPM1m acute myeloid leukemia (AML) with measurable residual disease (MRD) negativity and prolonged overall survival (5–7 months). While all menin inhibitors result in on-target blast differentiation with clinical sequelae (“differentiation syndrome”) in 10% to 20% of patients, not all menin inhibitors are the same, with differing safety, toxicity (heartrate corrected QT interval (QTc) prolongation, cytopenias), and pharmacokinetic profiles. Acquired mutations in the menin gene described in 39% of post-revumenib relapses have not been identified following other inhibitors (ziftomenib, bleximenib), prompting new questions about resistance mechanisms. These promising results swiftly led to the launch of multiple trials of menin inhibitors combined with intensive (cytarabine and anthracycline) and nonintensive (venetoclax and hypomethylating) chemotherapy backbones. To date, these triplets have yielded high response rates (ie, ≥80% in de novo, 50-70% in relapsed) with most patients achieving MRD negativity and prolonged one-year survival. Ongoing/pending phase 3 trials will clarify whether menin blockade should be incorporated into frontline and maintenance regimens for all patients with KMT2A rearranged or NPM1 mutant disease. In the current era, menin inhibition remains a key pillar of the success of precision medicine for AML therapy.

2025-11-01·CURRENT OPINION IN ONCOLOGY

The role of menin inhibitors in acute myeloid leukemia

Review

作者: Marconi, Giovanni ; Isidori, Alessandro

Purpose of review:

Acute myeloid leukemia (AML) characterized by NPM1 mutations or KMT2A rearrangements depends on abnormal epigenetic programs mediated by menin, a critical scaffold protein for sustaining the expression of oncogenic HOX/MEIS1 genes. Therefore, menin inhibitors have become a promising class of AML treatments.

Recent findings:

Early-phase trials have shown that agents such as revumenib, ziftomenib, bleximenib, and enzomenib are active, particularly in relapsed/refractory disease, with 23–48% of patients achieving composite complete remission. However, the durability of single-agent treatment remains limited, and resistance mechanisms, such as MEN1 mutations or transcriptional reprogramming, have been identified. Consequently, combination approaches involving venetoclax, hypomethylating agents, or chemotherapy are being investigated to improve response depth and duration. Recent SAVE, KOMET-007, and cAMeLot-2 trials have demonstrated high overall response rates (68%-100%) and encouraging MRD-negative complete remissions when combining menin inhibitors with venetoclax-based regimens. This has been observed even in patients who have previously received venetoclax. Combinations with intensive chemotherapy (e.g., 7 + 3) in the frontline setting have also yielded high CRc rates (up to 94% in NPM1-mutated AML) without exacerbating toxicity.

Summary:

These findings justify the integration of menin inhibitors into the AML therapeutic landscape, and support ongoing randomized trials to confirm their benefit in both frontline and relapse or refractory settings.

2025-09-01·CRITICAL REVIEWS IN ONCOLOGY HEMATOLOGY

Menin inhibitors in KMT2A-rearranged and NPM1-mutated acute leukemia: A scoping review of safety and efficacy

Article

作者: Kalfah, Anas ; Dali, Sara Al ; Mohamed, Shehab F ; Al-Mashdali, Abdulrahman F

BACKGROUND:

Menin inhibitors represent a novel therapeutic approach targeting the Menin-KMT2A interaction in acute leukemias with KMT2A rearrangements or NPM1 mutations. This scoping review synthesizes current clinical evidence for emerging Menin inhibitors in development.

METHODS:

We systematically analyzed clinical trials, conference proceedings, and regulatory documents regarding Menin inhibitors in clinical development through December 2024. Primary outcomes included response rates, minimal residual disease (MRD) status, and safety profiles.

RESULTS:

Thirteen clinical trials investigating six Menin inhibitors (Revumenib, Ziftomenib, Bleximenib, BMF-219, DS-1594, and Enzomenib) were identified. Revumenib demonstrated consistent efficacy across five pivotal trials, achieving MRD-negative rates of 70-90 % in both KMT2A-rearranged and NPM1-mutated leukemias, leading to FDA approval in November 2024. Ziftomenib showed particular efficacy in NPM1-mutated cases but exhibited a higher incidence of differentiation syndrome (30 %) in KMT2A-rearranged patients. Bleximenib reported a 93 % overall response rate, pending MRD validation. Early resistance emergence, primarily through MEN1 mutations, was observed across trials, emerging as early as two treatment cycles.

CONCLUSIONS:

Menin inhibitors demonstrate promising clinical activity in molecularly defined leukemias, with Revumenib establishing proof-of-concept for this therapeutic approach. However, challenges remain, including resistance development, optimal timing of therapy initiation, and determination of effective combination strategies. Larger randomized trials with extended follow-up are needed to establish long-term efficacy and safety profiles. The rapid clinical development of multiple agents in this class suggests an expanding role for Menin inhibitors in leukemia treatment paradigms.

项与 Enzomenib 相关的新闻（医药）

2026-03-23

·药事纵横

破局耐药与毒性：从单药瓶颈到精准“三联”，Menin抑制剂如何改写高危AML生存预后？

急性髓系白血病（AML）的治疗格局正在经历一场深刻的范式转变。过去几十年间，以“7+3”方案（阿糖胞苷联合蒽环类药物）为基础的强化疗 followed by 异基因造血干细胞移植（allo-HSCT）一直是治疗的金标准。然而，对于携带特定高危分子特征的患者群体，尤其是赖氨酸甲基转移酶2A重排（KMT2Ar）和核磷蛋白1突变（NPM1m）的AML患者，传统疗法往往难以实现持久的疾病控制，复发率高且预后不佳。随着对白血病发生机制理解的深入，靶向治疗时代应运而生。继FLT3抑制剂和IDH1/2抑制剂之后，阻断Menin-KMT2A蛋白相互作用成为了近年来最具突破性的治疗策略。2024年11月，首款Menin抑制剂Revumenib获得加速批准，标志着这一类药物的正式登场。然而，单药治疗虽能诱导缓解，却面临分化综合征（DS）、心脏毒性（QTc延长）以及获得性耐药等挑战。当前，临床研究的焦点已迅速从单药转向联合治疗。多项早期临床试验数据显示，Menin抑制剂与强化疗或去甲基化药物（HMA）及维奈克拉（Venetoclax）组成的“三联疗法”，在初治和复发/难治（R/R）患者中均展现出令人瞩目的疗效，总缓解率（ORR）显著提升，微小残留病灶（MRD）阴性率大幅提高。本文基于最新权威综述，深入探讨Menin抑制剂三联疗法的疗效突破、安全性管理策略以及针对耐药机制的应对之道，旨在为临床医生提供科学、客观的决策参考。一、机制溯源：为何Menin成为关键靶点？要理解Menin抑制剂的疗效，首先需明确其作用机制。尽管KMT2Ar和NPM1m AML的遗传起源不同，但两者在致病机制上存在惊人的共性：它们都高度依赖Menin蛋白来维持异常的HOX-MEIS转录程序。 Menin是由MEN1基因编码的染色质支架蛋白。在KMT2Ar白血病中，Menin直接结合所有KMT2A融合蛋白N端的保守基序，将复合物锚定在HOX基因位点，并招募DOT1L等组蛋白甲基转移酶，从而维持HOXA9、HOXA10和MEIS1等高表达。这些转录因子是维持白血病干细胞自我更新和阻断分化的关键。而在NPM1m AML中，突变的NPM1蛋白易位至细胞核，与野生型KMT2A复合物及Menin相互作用，同样驱动这一致癌轴。 Menin抑制剂通过强效破坏Menin与KMT2A复合物之间的蛋白 - 蛋白相互作用，迫使复合物从染色质上解离，沉默HOX-MEIS转录程序。这一过程导致H3K79甲基化水平下降，增强子重编程，最终恢复髓系细胞的分化能力，诱导细胞周期停滞和凋亡。由于该结合口袋在所有KMT2A融合变体中高度保守，且在正常造血祖细胞中非必需，因此这类药物具有广泛的基因型覆盖率和良好的治疗指数。图1.Menin抑制剂在伴NPM1突变及KMT2A重排AML中的作用机制示意图二、单药治疗的奠基与局限：从Revumenib到新一代药物作为先行者，Revumenib在AUGMENT-101研究中确立了其地位。在重度预治的R/R KMT2Ar患者中，其复合完全缓解率（CCR）达到22%，总缓解率（ORR）高达63%，且61%的缓解者实现了MRD阴性。更重要的是，约40%的缓解者成功桥接了allo-HSCT，为治愈带来了希望。在NPM1m患者中，Revumenib也展现了类似的活性（ORR 47%）。随后，Ziftomenib、Enzomenib、Bleximenib等新一代药物相继问世。Ziftomenib在NPM1m患者中显示出33%的ORR，且无需因联用唑类抗真菌药而调整剂量，亦无显著的QTc延长风险。Enzomenib则凭借优异的药代动力学特征，在KMT2Ar和NPM1m患者中分别取得了65.2%和59%的ORR，且分化综合征发生率较低。Bleximenib和共价结合抑制剂BMF-219更是被设计用于克服潜在的耐药突变。然而，单药治疗的局限性也日益显现。首先，缓解深度和持续时间仍有限，中位缓解持续时间（DOR）多在4-7个月之间，难以长期控制疾病。其次，特异性毒性不容忽视。分化综合征（DS）作为“脱靶”效应，发生率在10%-20%之间，严重时可危及生命。此外，Revumenib特有的QTc间期延长问题限制了其在部分心脏病患者中的应用。最为严峻的是，约39%的Revumenib复发患者出现了MEN1基因的获得性突变，导致靶点结合能力下降，引发耐药。表1. Menin抑制剂三联疗法 vs. 单药治疗对比三、三联疗法的崛起：疗效的深度突破鉴于单药治疗的瓶颈，研究者迅速启动了Menin抑制剂与现有标准疗法联合的探索。目前的“三联疗法”主要指Menin抑制剂联合“维奈克拉+去甲基化药物（Ven/HMA）”或联合“强化疗（7+3）”。3.1在新诊断（ND）患者中的惊艳表现对于初治患者，三联疗法似乎正在重新定义缓解标准。在BEAT AML联盟的研究中，Revumenib联合Ven/Aza治疗老年ND患者，CR率高达67%，CCR达69.3%，且所有缓解者均实现MRD阴性。更为震撼的是KOMET-007试验的数据：Ziftomenib联合“7+3”方案治疗ND KMT2Ar或NPM1m患者，CR率达到了惊人的100%，MRD阴性率高达86%。Bleximenib联合“7+3”在ND患者中也取得了86%的CCR。这些数据强烈提示，Menin抑制剂有望成为此类患者的一线标准治疗。3.2在复发/难治（R/R）患者中的挽救价值对于既往治疗失败的患者，三联疗法同样展现了强大的挽救能力。SAVE试验评估了全口服方案（Revumenib+口服地西他滨/Cedazuridine+维奈克拉），在R/R患者中ORR高达82%，中位无进展生存期（PFS）延长至9.9个月，显著优于历史对照。值得注意的是，即便是在既往接受过维奈克拉治疗的患者中，Ziftomenib和Bleximenib的三联方案仍保持了50%-65%的ORR，证明了其克服BCL-2耐药潜力的可能性。3.3 MRD阴性与移植桥接三联疗法最核心的优势在于深度的MRD清除。多项研究显示，三联方案下MRD阴性率普遍超过60%-80%，远高于单药治疗。深度的分子学缓解不仅延长了生存期，更为更多患者创造了接受allo-HSCT的机会，这是目前唯一可能治愈AML的手段。四、安全性管理：差异化特征与应对策略随着给药强度的增加，三联疗法的安全性管理变得尤为关键。总体而言，毒性可控，但需精细化管理。4.1分化综合征（DS）的预防与处理 DS是Menin抑制剂类的标志性毒性，源于白血病细胞的快速分化。在三联疗法中，DS发生率略有上升（约15%-25%），但严重（≥3级）事件比例并未显著增加。关键在于早期识别（如不明原因发热、体重增加、呼吸困难）和及时干预。目前的标准策略包括预防性使用地塞米松、出现症状时立即暂停给药并加大激素剂量。Enzomenib等新一代药物显示出更低的DS发生率，可能与其药代动力学特性有关。4.2心脏毒性的分子特异性 QTc间期延长是Revumenib的主要限制因素，在任何级别的发生率可达25%-64%。这要求临床必须常规进行心电图监测和电解质管理，并避免联用其他延长QTc的药物。相比之下，Ziftomenib、Bleximenib和Enzomenib在临床试验中未显示出显著的QTc延长风险，这为有心脏基础疾病的患者提供了更安全的选择。这表明心脏毒性是分子特异性的，而非类效应。4.3血液学毒性的叠加效应当Menin抑制剂与Ven/HMA或强化疗联用时，骨髓抑制不可避免。在三联方案中，3-4级中性粒细胞减少和血小板减少的发生率可高达70%-80%。管理策略包括预防性使用抗生素、生长因子支持，以及灵活调整维奈克拉的给药天数（如从28天减至21天或14天）。值得庆幸的是，多数患者的血象可在疗程间歇期恢复，且未观察到长期的骨髓衰竭风险。五、耐药机制解析与未来应对尽管三联疗法疗效显著，但耐药仍是悬在头顶的达摩克利斯之剑。目前的耐药机制主要分为两类：5.1靶点内耐药（On-target）最主要的是MEN1基因的点突变（如M327I, G331R, T349M），这些突变改变了Menin蛋白的结合口袋，降低了药物亲和力，但保留了其与KMT2A的结合功能。这在Revumenib治疗后尤为常见（约39%）。应对策略：开发下一代抑制剂。例如，Bleximenib和共价结合抑制剂BMF-219被设计为能结合突变后的Menin蛋白或结合不同的口袋，临床前数据已显示其对突变株有效。此外，轮换使用不同结构的Menin抑制剂也可能是一种策略。表2. Menin抑制剂耐药机制及治疗应对策略 5.2靶点外耐药（Off-target）包括RAS通路突变（NRAS, KRAS, PTPN11）激活替代增殖信号，TP53突变导致凋亡受阻，以及PRC1.1复合物缺失引起的表观遗传重编程。应对策略：联合靶向治疗。针对RAS突变，可联合MAPK抑制剂或FLT3抑制剂；针对凋亡受阻，可联合MCL-1抑制剂；针对表观遗传逃逸，可联合DOT1L抑制剂或BRD4抑制剂。这种“双靶向”甚至“多靶向”策略可能是未来的主流方向。此外，动态监测至关重要。在治疗过程中及复发时，利用高灵敏度的NGS技术检测MEN1突变及其他克隆演变，将为后续治疗方案的选择提供关键依据。六、结语总的来说，Menin抑制剂三联疗法标志着KMT2Ar/NPM1m突变AML治疗迈入精准联合新纪元。相较于单药，该策略在初治及复发难治人群中显著提升了缓解深度与MRD阴性率，并有效桥接造血干细胞移植。尽管面临分化综合征、QTc延长及MEN1突变耐药等挑战，但通过新一代药物优化、毒性精细化管理及基于分子机制的联合阻断策略，临床获益有望进一步扩大。随着多项III期试验推进，三联方案有望确立为一线标准，最终改善高危AML患者的长期生存预后。参考文献： [1] Perner F, Gadrey JY, Armstrong SA, Kühn MWM. Targeting the Menin-KMT2A interaction in leukemia: Lessons learned and future directions. Int J Cancer. 2026 Jan 15;158(2):342-356. doi: 10.1002/ijc.35332. [2] Chen T, Kim G, Rahimi Y, Kamdar M, Fernandez-Hernandez E, Woan K, Tam EL, Yaghmour G. Clinical Integration of Menin Inhibitors in AML: Evolving Data and Therapeutic Perspectives. Oncol Res. 2026 Feb 24;34(3):4. doi: 10.32604/or.2025.072443. [3] Thakur RK, Wang ES. The promise of menin inhibitors: from approval to triplet regimens. Hematology Am Soc Hematol Educ Program. 2025 Dec 5;2025(1):599-606. doi: 10.1182/hematology.2025000755. 立即扫码加入药事纵横交流群

加速审批临床2期

2026-02-01

·儿血笔记

【Blood综述】Menin 抑制剂治疗急性髓系白血病

摘要急性髓系白血病（AML）是一种异质性血液系统恶性肿瘤，其特征是髓系祖细胞的（寡）克隆性扩增。尽管治疗取得了一定进展，但 AML 的治愈仍然具有挑战性，尤其是对于具有特定基因异常的患者。Menin 抑制剂已成为一种极具前景的治疗方法，可靶向 AML 的关键遗传驱动因素，如 KMT2A 重排和 NPM1 突变。本文综述了 Menin 抑制剂的临床价值，重点阐述了其作用机制、疗效、安全性以及改变 AML 治疗格局的潜力。引言基因转录异常会导致多种生物学过程紊乱，这被视为癌症的特征，也是急性髓系白血病（AML）等髓系恶性肿瘤多步骤发生发展的核心机制 ¹⁻²。基因调控异常可能由染色体异常、基因突变或表观遗传改变（即 DNA 及相关蛋白的化学修饰，可调控基因表达但不改变 DNA 序列本身）引起。参与表观遗传调控的基因（如 DNMT3A、TET2、ASXL1、IDH1 和 IDH2）在 AML 中常发生突变 ³。表观遗传调控机制包括 DNA 甲基转移酶（DNMTs）在调控区 CpG 岛添加甲基、组蛋白修饰及非编码 RNA 调控等⁴。与染色体异常和基因突变不同，表观遗传改变具有潜在可逆性，因此成为癌症治疗的理想靶点⁵⁻¹¹。一项纳入 600 余名老年 AML 患者的前瞻性随机试验显示，10 天疗程的地西他滨治疗与强化化疗的生存率相当，这充分体现了 DNA 去甲基化药物的治疗潜力 ¹²。组蛋白是细胞核内的关键蛋白，在 DNA 组装和压缩形成染色质过程中发挥重要作用。组蛋白如同线轴，DNA 缠绕其上形成核小体，每个核小体由 8 个核心组蛋白（H2A、H2B、H3、H4 各 2 个）组成。组蛋白的翻译后修饰会影响基因表达和染色质结构⁴⁻¹³。组蛋白修饰的多样性体现了其转录调控的复杂性，主要包括：①赖氨酸残基乙酰化（通常与基因激活相关）；②赖氨酸或精氨酸残基甲基化（可激活或抑制基因表达）；③组蛋白上丝氨酸、苏氨酸或酪氨酸残基磷酸化（常参与细胞分裂和 DNA 修复过程中的染色质结构调控）；④赖氨酸残基泛素化（可介导组蛋白降解或改变染色质结构）。这些修饰通过被称为 “写入器”“读取器” 和 “擦除器” 的特异性酶动态调控基因转录 ¹⁴。目前已开发出多种针对这些酶的抑制剂，以影响表观遗传编程及致癌转录程序，例如组蛋白去乙酰化酶抑制剂（HDAC 抑制剂）¹⁴⁻¹⁵。尽管 HDAC 抑制剂最初被认为是治疗髓系恶性肿瘤的潜在药物，尤其是与 DNA 去甲基化药物联合使用时，但尚未达到预期疗效 ¹⁶。组蛋白在转录激活（转录起始）和延伸（RNA 聚合酶沿基因移动合成 RNA）过程中起关键作用。基础转录因子、聚合酶 Ⅱ 招募以及组蛋白修饰介导的染色质开放结构之间的复杂相互作用，共同调控基因表达程序。Menin 和三胸蛋白 KMT2A 已被证实在此过程中发挥重要作用。Menin 蛋白 Menin 由 MEN1 基因编码，该基因的种系功能缺失突变与 1 型多发性内分泌腺瘤病（MEN1）综合征相关。Menin 作为支架蛋白，可与多种伙伴相互作用，调控基因表达和细胞稳态，在表观遗传调控中至关重要。Menin 充当 H3K4（即组蛋白 3 第 4 位赖氨酸）甲基转移酶 KMT2A（原称 MLL，混合谱系白血病 1）与 LEDGF（晶状体上皮衍生生长因子）之间的衔接蛋白（图 1）¹⁷⁻¹⁸。此外，Menin 还可与精氨酸甲基转移酶 PRMT5、H3K9 甲基转移酶 SUV39H1 及多种转录因子相互作用 ¹⁹。Menin 通过与 KMT2A 复合物及相关染色质修饰因子结合，可激活致癌转录程序，包括上调 HOXA 基因簇和 MEIS1 的表达。值得注意的是，Menin 在内分泌组织中发挥抑癌作用，而在白血病中则作为致癌辅因子。 HOXA/MEIS1 表达上调是 NPM1 突变型 AML 的标志性特征 ²⁰⁻²¹。NPM1 突变型 AML 约占所有 AML 的 20%-30%，通常核型正常，与其他 AML 亚型相比预后相对较好，但结局仍受额外遗传因素和治疗反应的影响 ²²。在 AML 中，NPM1 蛋白 C 端核仁定位信号的突变导致其异常定位于细胞质 ²²。近期研究表明，部分突变型 NPM1 蛋白仍存在于细胞核内，并与 KMT2A 共同占据特定染色质靶点（如 HOXA 基因座）²³⁻²⁴。HOXA/MEIS1 上调也可见于 KMT2A 重排白血病，约占所有白血病的 5%-10%²⁵。根据 ELN-2022 分类标准，最常见的重排类型 MLLT3::KMT2A 被归为中危，而其他 KMT2A 重排则与不良预后相关 ²⁶。KMT2A 重排白血病常见于年轻患者（包括 70%-80% 的婴儿和儿童），成人中也有发生（60 岁以上 AML 患者中占比 < 1%）。KMT2A 重排白血病由涉及 KMT2A 基因的染色体易位或倒位定义，产生驱动白血病发生的融合蛋白 ²⁵。2005 年的一项研究发现，在小鼠模型中敲除 Men1 基因可预防 KMT2A 重排白血病的发生，首次证实 MLL 融合蛋白与 Menin 的直接相互作用是白血病发生的关键 ²⁷。这一发现推动了小分子 Menin 抑制剂的研发，2012 年的首篇相关发表突显了该策略的巨大潜力 ²⁸。重要的是，2016 年有研究表明 NPM1 突变型 AML 细胞同样依赖 Menin 与野生型 KMT2A 蛋白的相互作用，这将 Menin 抑制剂的治疗潜力扩展到了另一种更常见的 AML 亚型 ²⁶。Menin 抑制剂对 Menin 在白血病发生中作用的深入理解，以及药物研发技术的最新进展，促成了高选择性小分子 Menin 抑制剂的开发。高通量筛选和结构生物学技术助力鉴定和优化了可有效抑制 Menin-KMT2A 相互作用的化合物（即 Menin 抑制剂），这些化合物通过特异性靶向 Menin 表面的疏水口袋发挥作用。在证实 Menin-KMT2A 相互作用是 MLL 重排白血病的治疗靶点后 ²⁷，新型 Menin-KMT2A 相互作用抑制剂的研发随之展开 ²⁹。不久后研究证实，这些 Menin-KMT2A 抑制剂对 NPM1 突变型 AML 同样有效 ³⁰。近年来，具有更优药物特性的 Menin 抑制剂已被报道对这两种 AML 亚型均有疗效 ³¹。Menin 抑制剂 VTP50469 在侵袭性患者来源的异种移植模型中，可诱导 KMT2A 重排和 NPM1 突变型 AML 实现长期缓解 ³²⁻³³。目前，已有 7 种 Menin 抑制剂处于 AML 治疗的不同临床阶段：VTP50469 的后续药物 SNDX-5613（revumenib，瑞维鲁胺）、KO-539（ziftomenib，齐夫托米尼）、JNJ-75276617（bleximenib，布来昔米尼）、DSP-5336、DS-1594、BN104 和 BMF-219。表 1 总结了目前可获得的主要疗效和安全性临床数据。最先进的 Menin 抑制剂瑞维鲁胺用于复发 / 难治性（R/R）急性白血病的首次人体 Ⅰ 期临床试验（AUGMENT-101，NCT04065399）结果已公布 ³⁴。该研究纳入 68 名经多线治疗的患者（中位年龄 42 岁，中位既往治疗线数 4 线，46% 接受过异基因造血干细胞移植），其中 68% 为 KMT2A 重排，21% 为 NPM1 突变，最终确定了瑞维鲁胺的 Ⅱ 期推荐剂量。3 级及以上治疗相关不良事件发生率较低，唯一的剂量限制性毒性为无症状 QTc 间期延长。瑞维鲁胺单药口服治疗的总缓解率（ORR）为 53%，完全缓解 / 伴不完全血液学恢复的完全缓解（CR/CRh）率为 30%。近期公布的 AUGMENT-101 试验 Ⅱ 期部分结果显示，94 名 KMT2A 重排患者中，3 级及以上不良事件包括发热性中性粒细胞减少（37%）、分化综合征（16%）和 QTc 间期延长（13%）；57 名可评估疗效的患者中，CR+CRh 率为 23%，总缓解率为 63%（其中 68% 无微小残留病）³⁵。NPM1 突变患者的 Ⅱ 期试验结果尚未公布。瑞维鲁胺在 R/R 白血病中展现的良好安全性和疗效数据，以及 Menin 抑制剂与维奈克拉联合使用的潜在临床价值，推动了多项研究的开展，包括在适合强化化疗的患者中评估瑞维鲁胺联合强化化疗的疗效，以及在不适合强化化疗的患者中评估其与去甲基化药物和维奈克拉联合使用的价值 ³⁶。Beat AML 试验（瑞维鲁胺联合阿扎胞苷和维奈克拉）和 SAVE 试验（瑞维鲁胺联合地西他滨 / 西达本胺和维奈克拉）在初治患者中的初步结果显示，尽管样本量较小，但均取得了 100% 的缓解率 ³⁷⁻³⁸。类似地，KOMET-001 试验（n=20）评估了齐夫托米尼治疗 R/R AML 的疗效，结果显示安全性可控，疗效令人鼓舞，完全缓解率为 40%，总缓解率为 45%³⁹。正在进行的 Ⅰ 期 KOMET-008 试验正在研究齐夫托米尼联合吉瑞替尼、FLAG-IDA 方案（氟达拉滨、阿糖胞苷、粒细胞集落刺激因子和伊达比星）或小剂量阿糖胞苷治疗 R/R NPM1 突变或 KMT2A 重排 AML 的疗效。瑞维鲁胺和齐夫托米尼均已获得美国食品药品监督管理局（FDA）的突破性疗法认定。布来昔米尼的 Ⅰ 期研究（NCT04811560；n=58）显示，不良事件可控，最高剂量组的总缓解率为 50%⁴¹。布来昔米尼联合阿扎胞苷和维奈克拉治疗 R/R AML 的 ⅠB 期数据（n=45）显示，50mg 每日两次队列（n=21）的总缓解率为 86%⁴²。 Menin 抑制剂的安全性特征总体良好，大多数不良反应可控且可逆。常见副作用包括胃肠道症状、血细胞减少、QTc 间期延长和分化综合征。重要的是，Menin 抑制剂未发现明显的脱靶毒性，使其成为长期治疗的潜在选择。长期安全性数据仍在收集中，但早期结果表明 Menin 抑制剂可安全地长期给药。正在进行的研究正在进一步评估这些药物与其他疗法（如化疗和靶向药物）联合使用的安全性和耐受性。遗留问题与未来展望耐药性的出现是癌症治疗中反复面临的挑战。Menin-KMT2A 抑制剂研发及临床试验开展后不久，其耐药机制便被报道（图 1）。在 CRISPR 突变筛选、患者来源异种移植模型以及 AUGMENT-101 试验的患者（38%）中，均发现了 MEN1 突变，该突变可减弱瑞维鲁胺与 Menin 的结合，但不影响 Menin-KMT2A 相互作用⁴³。未来研究应阐明联合治疗是否可降低 MEN1 突变的发生率。在部分无 MEN1 突变的患者中也观察到了耐药现象⁴³。研究表明，对 Menin-KMT2A 抑制剂的持续敏感性依赖于非经典多梳蛋白（PRC1.1）介导的靶基因抑制⁴⁴⁻⁴⁵。当 Menin-KMT2A 介导的 HOXA 和 MEIS1 靶基因表达受抑时，需要表观遗传抑制机制维持这些基因座的闭合和抑制状态。因此，非经典 PRC1.1 信号通路的缺失可能也是 Menin-KMT2A 抑制剂的耐药机制之一。此外，研究表明 Menin-KMT2A 抑制剂的疗效不仅依赖于抑制自我更新基因表达程序，还需要切换至 KMT2C/D 介导的髓系分化基因表达程序⁴⁴。另外，Menin-KMT2A 抑制后可上调 MHCⅠ 类和 Ⅱ 类分子的表达⁴⁶⁻⁴⁷，表明白血病细胞免疫逃逸的减少可能也是 Menin 抑制剂发挥疗效的机制之一。最后，尽管已明确 NPM1 突变或 KMT2A 重排的 AML 患者尤其可能从 Menin 抑制剂治疗中获益，但这些遗传亚组中仍有部分患者对 Menin-KMT2A 抑制的反应较差。阐明这种敏感性差异的潜在机制至关重要。相反，Menin 抑制剂的获益人群可能扩展至 NUP98 重排⁴⁸、UBTF 串联重复白血病⁴⁹和 CEBPA 突变⁵⁰的 AML 患者。未来需要开展更多研究，以优化 Menin 抑制剂获益患者的筛选，并制定规避或预防耐药的策略。结论 Menin 抑制剂已成为 AML 治疗中极具前景的新型靶向疗法，为 KMT2A 重排和 NPM1 突变型 AML 患者带来了改善预后的希望。通过阻断 Menin 的致癌功能，Menin 抑制剂可有效靶向白血病发生的潜在驱动因素，并实现持久缓解。随着临床研发的推进，Menin 抑制剂有望改变 AML 的治疗格局，改善这一难治性疾病患者的预后。未来研究应聚焦于优化 Menin 抑制剂在联合治疗方案中的应用，鉴定疗效生物标志物，并探索其在其他 AML 亚型及其他血液系统恶性肿瘤中的疗效。参考文献：Huls G, Woolthuis CM, Schuringa JJ. Menin inhibitors in the treatment of acute myeloid leukemia. Blood. 2025 Feb 6;145(6):561-566. doi: 10.1182/blood.2024026232. PMID: 39719041.

2025-12-08

·PRNewswire

Sumitomo Pharma America Presents New Investigational Data on Enzomenib and Nuvisertib at the 2025 American Society of Hematology Annual Meeting and Exposition

New investigational data from Phase 1/2 study of enzomenib (DSP-5336) in patients with relapsed/refractory acute myeloid leukemia (AML) show clinical activity in various leukemia subtypes driven by genomic alterations Promising preliminary data, particularly in patients without prior venetoclax or menin inhibitor exposure, seen in Phase 1 study of enzomenib in combination with venetoclax and azacitidine in patients with relapsed/refractory AML Preliminary data from Phase 1/2 study of nuvisertib (TP-3654) in combination with momelotinib in patients with relapsed/refractory myelofibrosis (MF) with anemia show treatment combination appears to be well tolerated with early clinical activity and improvements in spleen and symptom responses MARLBOROUGH, Mass., Dec. 8, 2025 /PRNewswire/ -- Sumitomo Pharma America, Inc. (SMPA) today presented new clinical data supporting further development of enzomenib, an investigational, oral selective menin inhibitor being researched for the treatment of relapsed or refractory acute leukemia, and nuvisertib, an oral investigational highly selective small molecule PIM1 kinase inhibitor, being researched for the treatment of relapsed or refractory myelofibrosis (MF), at the 67th American Society of Hematology (ASH) Annual Meeting and Exposition. Updated Data Shared with the Use of Enzomenib in Acute Myeloid Leukemia Updated preliminary data were presented from the ongoing Phase 1/2 study of enzomenib monotherapy, which as of October 4, 2025, included 116 total patients with acute leukemia, most of whom (93.1%, 108/116) had acute myeloid leukemia (AML) with a median of two prior regimens. Genomic abnormalities of leukemia subtypes including KMT2A rearrangement (KMT2Ar) were documented in 61 patients (52.6%), NPM1 mutation (NPM1m) in 34 patients (29.3%), and other HOXA9/MEIS1-driven abnormalities in 21 patients (17.7%). Enzomenib was escalated from 40 mg twice a day (BID) to 400 mg BID with no dose-limiting toxicities (DLTs). Treatment-related adverse events (TRAEs) observed in at least 10% of patients were nausea (16.4%), and vomiting (11.2%). Differentiation syndrome (DS) was reported in 12.9% of patients and did not result in patient deaths, study discontinuations, or dose reductions of enzomenib. No treatment-related deaths were observed in the study. Dose-dependent increases in exposure were observed, particularly at doses greater than 140 mg BID. Little to no drug accumulation was observed, and CYP3A4 inhibitor azoles did not have a significant impact on exposure. In patients with KMT2Ar, dose optimization of 200, 300, and 400 mg BID is complete, and the RP2D has been determined as 300 mg BID. At RP2D, in patients with KMT2Ar who had not received prior treatment with a menin inhibitor (n = 15), the objective response rate (ORR) was 73.3% and CR+CRh was 40%. Across the optimization dose levels, the duration of CR+CRh (n = 11) was 12.5 months and in all optimization patients (n = 39) median overall survival (mOS) was 11.8 months. For patients with NPM1m AML, dose optimization is ongoing at 200, 300, and 400 mg BID with a focus on 200 and 300 mg BID in patients who have not received a prior menin inhibitor. In the NPM1m dose optimization population (n=25, pts who received ≥ 200 mg BID), ORR is 52% and CR+CR is 44% with a duration of CR+CRh of 5.7 months. The mOS was 8.5 months. "Despite improved understanding of the genetic factors of certain high-risk subtypes in acute leukemias, poor prognosis for patients remains a significant unmet need," said Naval G. Daver, M.D., professor and director of the Leukemia Research Alliance Program in the Department of Leukemia at MD Anderson Cancer Center in Houston. "The data from this ongoing Phase 1/2 study continue to show that enzomenib exhibits promising clinical activity, with encouraging overall and complete response rates, duration of response, and no significant drug interactions with azoles in patients with relapsed or refractory KMT2Ar or NPM1m AML. As an intentionally designed oral therapy to inhibit menin and KMT2A protein interaction, these encouraging clinical results combined with a promising safety profile support the potential of enzomenib as a therapeutic option for relapsed or refractory acute leukemia patients with KMT2A-rearranged or NPM1-mutated subtypes of the disease." Also presented were preliminary results of a Phase 1 study of enzomenib at dose levels of 140 mg, 200 mg, and 300 mg BID in combination with azacitidine and venetoclax (VEN/AZA) in patients with relapsed or refractory AML with KMT2Ar or NPM1m. VEN was administered on days 1-14 of a 28-day study cycle, AZA on days 1-7, and enzomenib was administered on days 1-28 with and without azole antifungal agents. A total of 40 patients were enrolled, of which 18 had KMT2Ar (45%) and 22 (55%) had NPM1m. The median number of prior regimens was 2, with 15 patients having received prior venetoclax (37.5%) and 11 patients (27.5%) a prior menin inhibitor. There were no DLTs observed in the 40 patients enrolled. Hematologic TRAEs related to any regimen component observed in at least 15% of patients included thrombocytopenia (45%), leukopenia (35%), neutropenia (30%), anemia (22.2%), and lymphopenia (15%). Non-hematologic TRAEs were nausea (25%), diarrhea (20%), and AST increased and constipation (15% each). Any-cause QT interval prolongation was reported in 4 patients (10%) with no grade 3 or higher events; no cases were considered related to enzomenib. There were also 4 events of non-serious DS with 0 events grade 3 or higher. Pharmacokinetic data indicated that there were no significant drug-drug interactions between enzomenib and VEN. As of the clinical data cutoff on October 4, 2025, clinical activity data is available for 26 of the 40 total patients as 11 patients were still in Cycle 1 (n = 9) or Cycle 2 (n = 2), and 3 patients had cutaneous leukemia without measurable disease in the bone marrow (bone marrow blasts <5%). Promising preliminary clinical activity has been observed, particularly in patients without prior VEN or menin inhibitor exposure (N=13). The ORR is 85% (11/13) and the composite complete remission (CRc) rate is 62% (8/13). Local MRD assessments were available in 9 patients and 7/9 (78%) achieved MRD negativity as of the cut-off. These data support evaluating enzomenib with VEN/AZA in patients with newly diagnosed AML. Study arms are being added to investigate the combination regimen for patients with newly diagnosed disease. Enzomenib will be administered at 200 mg or 300 mg BID using VEN/AZA administered according to the FDA label. Enrollment of newly diagnosed patients with KMT2Ar or NPM1m AML will begin in early 2026. Nuvisertib in Patients with Relapsed or Refractory (R/R) MF For the first time, clinical data were presented from the ongoing global Phase 1/2 study evaluating the safety and efficacy of nuvisertib in combination with momelotinib (MMB) in 18 patients with R/R MF with anemia. All enrolled patients in the study had previously been treated with a JAK inhibitor, the current standard of care for patients with MF, and 61% of patients had high molecular risk mutation. Preliminary data showed that the treatment with nuvisertib and MMB combination appeared well tolerated, with early clinical activity observed, including ³50% total symptom score reduction (TSS50 response) in 58% of patients with an absolute reduction in all individual symptoms, a spleen volume reduction ³ 25% (SVR25 response) in 50% of patients, anemia improvement, and cytokine modulation in patients with relapsed or refractory MF with anemia. These preliminary data, collected as of October 15, 2025, support further development of nuvisertib in combination with MMB as a potential treatment option for patients with MF. Additionally, data presented from the ongoing global Phase 1/2 study of nuvisertib in patients with relapsed or refractory MF (N=77) showed that nuvisertib monotherapy continued to be well tolerated with no DLTs and limited myelosuppression. The results showed that treatment with nuvisertib monotherapy led to SVR25 response in 20% of patients, TSS50 response in 45% of patients with absolute reduction in all individual symptoms. Data also showed that treatment with nuvisertib resulted in significant cytokine modulation over time, correlating with spleen and symptom responses and one-year overall survival rate of 81%. "Patients living with myelofibrosis with anemia usually have a dismal prognosis, still continue to face limited treatment options," said John Mascarenhas, M.D., Director of the Center of Excellence for Blood Cancers and Myeloid Disorders, Icahn School of Medicine at Mount Sinai, New York. "The promising preliminary results from the combination of nuvisertib and momelotinib underscore the urgent need for new therapeutic approaches that may offer meaningful clinical benefits to a difficult to treat disease." "We are excited to present the first-ever myelofibrosis data with a momelotinib-based combination, specifically nuvisertib in combination with momelotinib. The development of innovative therapies—both alone and in combination with other treatments—are critical for physicians and patients with blood cancers such as AML or MF who are in urgent need of new effective therapies," said Jatin Shah, M.D., Chief Medical Officer, Oncology, SMPA. "Based on these updated preliminary data presented at ASH, which continue to show promising clinical activity and safety profiles for both enzomenib and nuvisertib, we remain committed to accelerate the clinical development in these programs with the ultimate goal of improving patient outcomes." About Leukemia Leukemia is a type of cancer that forms in blood-forming tissue, characterized by the uncontrolled growth of blood cells, usually white blood cells, in the bone marrow. Acute leukemia, a form of leukemia, requires immediate treatment as blood cells multiply rapidly leading to a sudden onset of symptoms.1 Approximately 30% of patients with AML have NPM1 mutations,2 and 5%-10% of patients with AML have KMT2A rearrangements.3 About Myelofibrosis (MF) MF is a rare type of blood cancer that is characterized by the buildup of fibrous tissue in the bone marrow, which can affect the production of blood cells. This buildup is caused by dysregulation in the JAK signaling pathway. MF is a serious and rare disease with 0.7 new cases per 100,000 people worldwide each year.4 About Enzomenib (DSP-5336) Enzomenib is an investigational, oral, small molecule inhibitor of the menin and Lysine (K)-specific methyltransferase 2A (KMT2A) protein interaction, a key interaction in acute leukemia and other tumor cell proliferation and growth. Menin is a scaffold nuclear protein, which plays key roles in gene expression and protein interactions involved in many biological pathways, including cell growth, cell cycle, genomic stability, and hematopoiesis.5,6 In preclinical studies, enzomenib has shown selective growth inhibition in human acute leukemia cell lines with KMT2A rearrangements or NPM1 mutations.5,7 Enzomenib reduced the expression of the leukemia-associated genes HOXA9 and MEIS1 and increased the expression of the differentiation gene CD11b in human acute leukemia cell lines with KMT2A rearrangements and NPM1 mutation.8,9 The safety and efficacy of enzomenib is currently being clinically evaluated in a Phase 1/2 dose-escalation/dose-expansion study in patients with relapsed or refractory acute leukemia (NCT04988555). Additionally, the registrational Phase 2 Horizen-1 R/R mono AML/ALL (KMT2Ar + NPM1m) study is now open for enrollment. The FDA granted Orphan Drug Designation for enzomenib for the indication of acute myeloid leukemia in June 2022. The FDA granted Fast Track Designation for enzomenib for the indication of relapsed or refractory acute myeloid leukemia with KMT2Ar or NPM1m in June 2024. Japan's Pharmaceuticals and Medical Devices Agency (PMDA) granted Orphan Drug Designation for enzomenib for the indication of relapsed or refractory acute myeloid leukemia with KMT2Ar or NPM1m in September 2024. About Nuvisertib (TP-3654) Nuvisertib is an oral investigational selective inhibitor of PIM1 kinase, which has shown potential antitumor and antifibrotic activity through multiple pathways, including induction of apoptosis in preclinical models.10,11 Nuvisertib was observed to inhibit proliferation and increase apoptosis in murine and human hematopoietic cells expressing the clinically relevant JAK2 V617F mutation.10 Nuvisertib alone and in combination with ruxolitinib showed white blood cell and neutrophil count normalization and reduced spleen size and bone marrow fibrosis in JAK2 V617F and MPLW515L murine models of myelofibrosis.11 The safety and efficacy of nuvisertib is currently being clinically evaluated in a Phase 1/2 study in patients with intermediate- and high-risk myelofibrosis (NCT04176198). The FDA granted Orphan Drug Designation to nuvisertib for the indication of myelofibrosis in May 2022. The Japan Ministry of Health, Labour and Welfare (MHLW) granted Orphan Drug Designation to nuvisertib for the treatment of myelofibrosis in November 2024. The FDA granted Fast Track Designation to nuvisertib for the indication of myelofibrosis in July 2025. About Sumitomo Pharma Sumitomo Pharma Co., Ltd. is a global pharmaceutical company based in Japan with key operations in the U.S. (Sumitomo Pharma America, Inc.) and Canada (Sumitomo Pharma Canada, Inc.) focused on addressing patient needs in oncology, urology, women's health, rare diseases, cell & gene therapies and CNS. With several marketed products in the U.S., Canada, and Europe, and a diverse pipeline of early- to late-stage investigational assets, we aim to accelerate discovery, research, and development to bring novel therapies to patients sooner. For more information on SMPA, visit our website or follow us on LinkedIn. The Sumitomo corporate symbol mark is a trademark of Sumitomo Pharma Co., Ltd., used under license. SUMITOMO PHARMA is a trademark of Sumitomo Pharma Co., Ltd., used under license. SUMITOMO is a registered trademark of Sumitomo Chemical Co., Ltd., used under license. Sumitomo Pharma America, Inc., is a U.S. subsidiary of Sumitomo Pharma Co., Ltd. ©2025 Sumitomo Pharma America, Inc. All rights reserved. References Chennamadhavuni A, Lyengar V, Mukkamalla SKR, et al. Leukemia. [Updated 2023 Jan 17]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan-. Available from: Brandi ML, Agarwal SK, Perrier ND, Lines KE, Valk GD, Thakker RV. Multiple Endocrine Neoplasia Type 1: Latest Insights. Endocr Rev. 2021;42(2):133-170. doi:10.1210/endrev/bnaa031 Borkin D, Klossowski S, Pollock J, et al. Complexity of Blocking Bivalent Protein-Protein Interactions: Development of a Highly Potent Inhibitor of the Menin-Mixed-Lineage Leukemia Interaction. J Med Chem. 2018;61(11):4832-4850. doi:10.1021/acs.jmedchem.8b00071 Hernández-Boluda JC, Czerw T. Transplantation algorithm for myelofibrosis in 2022 and beyond. Best Pract Res Clin Haematol. 2022;35(2):101369. doi:10.1016/j.beha.2022.101369 Cierpicki T, Grembecka J. Challenges and opportunities in targeting the menin-MLL interaction. Future Med Chem. 2014;6(4):447-462. doi:10.4155/fmc.13.214 Matkar S, Thiel A, Hua X. Menin: a scaffold protein that controls gene expression and cell signaling. Trends Biochem Sci. 2013;38(8):394-402. doi:10.1016/j.tibs.2013.05.005 Kühn MW, Song E, Feng Z, et al. Targeting Chromatin Regulators Inhibits Leukemogenic Gene Expression in NPM1 Mutant Leukemia. Cancer Discov. 2016;6(10):1166-1181. doi:10.1158/2159-8290.CD-16-0237 Eguchi K, Shimizu T, Kato D, et al. Preclinical Evaluation of a Novel Orally Bioavailable Menin-MLL Interaction Inhibitor, DSP-5336, for the Treatment of Acute Leukemia Patients with MLL-Rearrangement or NPM1 Mutation. Blood 2021; 138 (Supplement 1): 3339. Available at: Daver N, Zeidner JF, Yuda J, et al. Phase 1/2 First-in-Human Study of the Menin-MLL Inhibitor DSP-5336 in Patients with Relapsed or Refractory Acute Leukemia. Blood 2023; 142 (Supplement 1): 2911. Available at: Dutta A, Nath D, Yang Y, et al. Genetic ablation of Pim1 or pharmacologic inhibition with TP-3654 ameliorates myelofibrosis in murine models. Leukemia. 2022;36(3):746-759. doi:10.1038/s41375-021-01464-2 Foulks JM, Carpenter KJ, Luo B, et al. A small-molecule inhibitor of PIM kinases as a potential treatment for urothelial carcinomas. Neoplasia. 2014;16(5):403-412. doi:10.1016/j.neo.2014.05.004 SOURCE Sumitomo Pharma America 21% more press release views with Request a Demo

临床结果快速通道孤儿药ASH会议临床1期

100 项与 Enzomenib 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
急性淋巴细胞白血病	临床2期	美国	Sumitomo Pharma America, Inc.	2022-02-28
急性淋巴细胞白血病	临床2期	日本	Sumitomo Pharma America, Inc.	2022-02-28
急性淋巴细胞白血病	临床2期	比利时	Sumitomo Pharma America, Inc.	2022-02-28
急性淋巴细胞白血病	临床2期	加拿大	Sumitomo Pharma America, Inc.	2022-02-28
急性淋巴细胞白血病	临床2期	法国	Sumitomo Pharma America, Inc.	2022-02-28
急性淋巴细胞白血病	临床2期	意大利	Sumitomo Pharma America, Inc.	2022-02-28
急性淋巴细胞白血病	临床2期	新加坡	Sumitomo Pharma America, Inc.	2022-02-28
急性淋巴细胞白血病	临床2期	韩国	Sumitomo Pharma America, Inc.	2022-02-28
急性淋巴细胞白血病	临床2期	西班牙	Sumitomo Pharma America, Inc.	2022-02-28
急性淋巴细胞白血病	临床2期	瑞士	Sumitomo Pharma America, Inc.	2022-02-28

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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


NCT04988555 (ASH2025)	临床1期	急性髓性白血病 KMT2A rearrangement \| NPM1 mutation	18	enzomenib+venetoclax+azacitidine (KMT2A-rearrangement or NPM1-mutation + Relapsed or Refractory Acute Myeloid Leukemia)	繭願範糧糧淵餘網願糧(範繭選願鏇襯鏇襯遞餘) = 醖夢選選範衊簾齋醖觸淵積餘觸餘襯襯鹹艱膚 (鏇艱夢繭築窪觸鹹齋鑰 ) 更多	积极	2025-12-06
NCT04988555 (Company_Website) 人工标引	临床1/2期	急性髓性白血病 \| 复发性急性髓细胞白血病 MLL Positive	84	enzomenib	繭蓋鏇獵鹽範蓋齋範鬱(衊鬱齋憲鹽觸廠鹽範鹽) = 鹹夢獵積鹹壓窪糧壓襯鹽廠繭襯鏇遞獵憲構鑰 (膚鬱壓齋襯襯範鏇簾襯 ) 更多	积极	2025-10-14
				enzomenib (overall population)	繭蓋鏇獵鹽範蓋齋範鬱(衊鬱齋憲鹽觸廠鹽範鹽) = 糧蓋廠獵蓋醖繭廠網範鹽廠繭襯鏇遞獵憲構鑰 (膚鬱壓齋襯襯範鏇簾襯 ) 更多
NCT04988555 (ASH2024) 人工标引	临床1/2期	急性白血病 KMT2A Rearrangement \| NPM1 Mutation \| HOXA9 Overexpression ... 更多	81	Enzomenib (DSP-5336)DSP-5336)	範願構觸繭遞窪觸鑰醖(顧憲壓觸衊壓構膚衊膚) = None 製膚構醖獵齋艱壓鹽壓 (繭積鏇網顧鑰獵構壓製 ) 更多	积极	2024-12-07
				Enzomenib (DSP-5336) 140 mg BID
NCT04988555 (EHA 12024 \| EHA 22024) 人工标引	临床1/2期	急性白血病 NPM1 Mutation \| KMT2A Rearrangement	58	DSP-5336	夢鏇艱餘蓋積繭簾築製(膚醖膚製襯艱蓋構醖膚) = 遞網鹽遞選糧衊遞顧醖鬱艱壓鹽鹽製壓獵鹹淵 (觸遞築蓋築繭顧獵簾淵 ) 更多	积极	2024-05-14
NCT04988555 (ASH2023) 人工标引	临床1/2期	复发性急性白血病 \| 难治性急性白血病	24	DSP-5336±concomitant azole therapy	築顧鏇觸廠餘鏇鹽餘遞(積廠網築餘糧糧築鬱顧) = 廠網糧顧襯憲蓋鹽齋獵窪壓鑰夢廠齋窪鏇網壓 (鬱夢膚鑰範製繭憲蓋顧 ) 更多	积极	2023-12-10
				DSP-5336±concomitant azole therapy (NPM1c)	齋廠鬱鬱壓築醖蓋鹹構(蓋範醖積壓窪範艱艱繭) = 構獵廠簾鹽獵衊鹹鏇顧衊壓顧壓憲鹽窪獵鬱衊 (遞醖醖鹹糧遞積鏇鬱夢 )