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

A phase 1/2 dose escalation / dose expansion study of Enzomenib (DSP-5336) in adult 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）

2025-09-01·CRITICAL REVIEWS IN ONCOLOGY HEMATOLOGY

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

Review

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.

2023-09-01·Journal of Cancer Research and Clinical Oncology

Targeting the undruggable: menin inhibitors ante portas

Review

作者: Desole, Maximilian ; Sica, Simona ; Dempke, Wolfram C M ; Chiusolo, Patrizia ; Schmidt-Hieber, Martin

Acute myeloid leukaemias harbouring a rearrangement of the mixed lineage leukaemia gene (MLL) are aggressive haematopoietic malignancies that relapse early and have a poor prognosis (event-free survival less than 50%). Menin is a tumour suppressor, however, in MLL-rearranged leukaemias it functions as a co-factor which is mandatory for the leukaemic transformation by interaction with the N-terminal part of MLL, which is maintained in all MLL-fusion proteins. Inhibition of menin blocks leukaemogenesis and leads to differentiation and, in turn, to apoptosis of leukaemic blasts. Furthermore, nucleophosmin 1 (NPM1) binds to specific chromatin targets, which are co-occupied by MLL, and menin inhibition has been shown to trigger degradation of mNPM1 resulting in a rapid decrease in gene expression and activating histone modifications. Therefore, disruption of the menin-MLL axis blocks leukaemias driven by NPM1 mutations for which the expression of menin-MLL target genes (e.g., MEIS1, HOX etc.) is essential. To date at least six different menin-MLL inhibitors are undergoing clinical evaluation as first- and second-line monotherapy in acute leukaemias: DS-1594, BMF-219, JNJ-75276617, DSP-5336, revumenib, and ziftomenib, however, only for revumenib and ziftomenib early clinical data have been reported. In the revumenib phase I/II AUGMENT-101 trial (N = 68) with very heavily pretreated AML patients the ORR was 53% with a CR rate of 20%. The ORR in patients harbouring MLL rearrangement of mNPM1 was 59%. Patients who achieved a response had a mOS of 7 months. Similar results have been reported for ziftomenib in the phase I/II COMET-001 trial. ORR was 40% and CRc was 35% in AML patients with mNPM1. However, outcome was worse in AML patients with a MLL rearrangement (ORR 16.7%, CRc 11%). Differentiation syndrome was a notable adverse event. The clinical development of novel menin-MLL inhibitors is well in line with the currently ongoing paradigm shift towards targeted therapies seen in the AML treatment landscape. Moreover, the clinical assessment of combinations of these inhibitors with established therapy options in AML could be the fuel for an improved outcome of MLL/NPM1 patients.

2022-10-01·Clinical Lymphoma Myeloma & Leukemia

AML-391 Phase 1/2, Open-Label, Dose Escalation, Dose Expansion Study of Menin Inhibitor DSP-5336 in Adult Patients With Acute Leukemia With and Without Mixed-Lineage Leukemia (MLL)– Rearrangement or Nucleophosmin 1 (NPM1) Mutation

Article

作者: Daver, Naval ; Stoudemire, Jay ; Dobrowolska, Hanna ; Hitron, Matthew ; Affinito, John ; Eguchi, Ken ; Watanabe, Akinobu ; Cai, Hongliang

Patients who relapse after initial acute leukemia (AL) treatment have median survival <6 months for AML and <1 y for ALL, especially AML or ALL with MLL rearrangements (MLLr) or relapsed AML with NPM1 mutations. Translocations of the MLL gene (5% to 10% of adult patients) produce an aggressive subtype, with a median overall survival (OS) of approximately 9 months. The NPM1 mutation (NPM1m) occurs in 30%-35% of adult de novo AML and is associated with a favorable prognosis. However, 40%-50% of these patients have concurrent FLT3-internal tandem duplication mutations negating this favorability. DSP-5336, a novel oral small-molecule, was developed to prevent menin protein binding to MLL fusion proteins that drive leukemogenesis. Nonclinical DSP-5336 studies showed selective growth inhibition against human AL cell lines with MLLr or NPM1m. Evidence of antitumor activity and survival advantage was demonstrated in 3 AML xenograft models with MLLr and/or NPM1m. Treatment with DSP-5336 may reduce leukemic cells and benefit patients with relapsed or refractory (R/R) MLLr or NPM1m AML or patients with R/R MLLr ALL. An open-label, single-arm, phase 1/2 study (NCT04988555) will evaluate the safety and efficacy of DSP-5336 and determine the recommended phase 2 dose (RP2D) in adults aged ≥18 y with relapsed/refractory AML or ALL after at least one line of therapy. Key inclusion criteria are ECOG performance status 0-2 and adequate organ function. Patients will be dosed twice daily in 28-day cycles. In phase 1, 21-30 patients will be enrolled into multiple dose cohorts (1-6 patients per dose level), with dose escalation determined using a two-parameter Bayesian logistic regression model. The RP2D will be informed by the maximum biologic effect or maximum tolerated dose, whichever is lower. The phase 2 study will include two arms (R/R AML with MLLr and R/R AML with NPM1m). Patients will be treated at the RP2D to evaluate clinical activity and safety and monitored using Bayesian posterior probability to optimize enrollment with Bayesian stopping rules. Bayesian monitoring of responses begins after the first 10 enrolled patients are evaluable for efficacy. This study is recruiting in the United States and Japan.

项与 Enzomenib 相关的新闻（医药）

2025-08-01

·医药代表

住友制药宣布，完成中国区业务剥离

继续和小伙伴们分享跨国药企动态。7 月 31 日，住友制药日本总部宣布，包括中国区在内的亚洲业务，已于当日完成向丸红集团的股权转让手续。住友制药表示，上述公司分割及股份转让已于 2025 年 7 月 31 日完成，住友制药（中国）有限公司及住友制药亚太公司（Sumitomo Pharma Asia Pacific Pte. Ltd., SMPAP）不再是住友制药的合并子公司。至此，原负责亚洲业务的中国子公司“住友制药（中国）有限公司”，以及统管除日本与中国以外亚洲国家和地区业务的住友制药亚太公司，自该日起将不再作为合并子公司纳入财务报表。住友制药计划将在 2025 财年第二季度将此次转让所得约 450 亿日元计入其他收益（核心利润内）。早在今年 4 月 1 日，住友制药就已宣布与丸红株式会社的全资子公司——丸红环球制药公司（Marubeni Global Pharma）签订了股权转让协议等相关文件，现在正是基于该协议完成了实际的股权交割手续（见 MRCLUB 历史消息：一外企宣布，转让中国区药品业务！高管继续减薪…）。为推进此次亚洲业务的转让，住友制药先将“住友制药（中国）有限公司”、SMPAP 及其子公司所运营的亚洲业务，以吸收分割方式转移至其新设的全资子公司。随后，住友制药将该新公司已发行股份的 60% 转让给丸红全球制药公司。本次正是根据该方案，此次完成了 60% 股权的转让，住友制药预计将因此获得约 450 亿日元的对价收入。此外，住友制药所持有的新公司剩余 40% 股份也计划于 2029 年 4 月之后转让给丸红环球制药公司，届时预计将再获得约 270 亿日元的对价。住友制药表示，将利用此次出售亚洲业务所获取的资金，加速推进公司业务重组战略的核心——北美三大主力产品（Orgovyx、Myfembree、Gemtesa）的快速成长，同时也将用于推进两款抗肿瘤新药（TP-3654、DSP-5336）的研发，以实现尽早恢复业绩并重启公司增长轨道。今日（8 月 1 日），住友制药中国公司也宣布了这个消息，根据同年 4 月 1 日公布的《有关亚洲业务公司分立（简易吸收式分立）以及签署同丸红 Global Pharma 株式会社的股份转让协议和股东间协议的通知》所述，相关资产与股权的剥离及首期股权转让已顺利完成。住友制药中国表示，“我司（原住友制药中国）已从住友制药株式会社中独立，正式成为丸红集团的一员，开启全新的征程。”相关阅读：四十年，一家跨国药企的中国故事医药人变身公益侠，全球公益接力正式版来了！2025国谈时间确定2024年全球药品销售20强百万人从社会“消失”，药企VR破局官宣了，国药股份董事长确定康方生物代表被查，官方结果公布一药企总裁被罚1500万，10年禁入美威胁200%医药关税，引多国警惕第十一批国采报量启动，55个品种阿斯利康开线下年会了，近4000人上市药企90后少帅，突然辞去所有职务三度亮相链博会，诺和诺德以“链”会友家族药企，创始人辞职，管理层更换9900万元创新药“破题”基金！申报开启骨科主任受贿两百万，分给他人一半多22年老将即将谢幕，诺华CFO完成交棒罗氏、默克人事变动，中国医药总经理辞职药企财务造假！多位高管将被重罚最新10个重点监控药品公布17家药企上榜25年《财富》中国500强百年跨国药企诚聘英才！BI招聘专场国家市监总局公告，一药企被罚近四千万第三家药企罚单落地，副总经理闪电辞职肺癌新突破！复宏汉霖WCLC“秀肌肉”中央巡视组进驻！李健被查又一跨国医药巨头CFO退休百济神州寻找发光的你（附全国职位）AZ前高管加盟，百时美施贵宝迎来新任CMO一医学专家被查，曾任三甲医院院长阿斯利康中国，架构调整拜耳新一轮招聘启动，这次机会不要错过中央巡视组进驻，前省卫健委主任主动投案18家药企上榜2025年《财富》世界500强诺和诺德新任总裁兼首席执行官确定国家药监局原副局长陈时飞被开除党籍医疗反腐，这两天多人被查MRCLUB原创作者招募中数十万精准会员每日阅读，助您快速提升个人品牌，扩大在医药行业及社会化媒体的影响力！（详情请访问网站http://wemr.club）医药代表伴您成长！

财报并购引进/卖出

2025-06-27

·肿瘤界

JHO丨主鸿鹄教授团队总结Menin抑制剂单药或联合疗法的最新数据

点击蓝字关注我们Menin抑制剂Menin 抑制剂靶向 KMT2A-Menin 蛋白-蛋白相互作用，抑制原始细胞增殖并诱导分化，已证实对以 HOXA 基因簇和 MEIS1 过表达为特征的急性白血病亚型（包括 KMT2A 重排、NPM1突变、NUP98重排和其他基因改变）具有潜在影响。继两种开创性的 menin 抑制剂 revumenib 和 ziftomenib 取得了可喜的结果后，其他 menin 抑制剂，包括bleximenib、enzomenib、BN-104和 HMPL506 也正在临床试验中进行研究。多项试验在2024年美国 ASH 年会上公布了其初步结果，包括5项单药临床试验和4项联合临床试验。首都医科大学附属北京朝阳医院和首都医学科学创新中心研究团队近日于Journal of Hematology& Oncology（IF=40.4）发表综述，系统总结了这些关键临床试验的核心研究成果。该论文由主鸿鹄教授与孙舒博士后担任共同通讯作者，研究工作由首都医科大学临床医学（阶平班）在读本科生曹格嘉与北京朝阳医院张海啸博士后共同完成（并列第一作者）。Menin抑制剂单药在2024年ASH年会上，展示了四种menin抑制剂（revumenib、bleximenib、enzomenib和BN-104）作为单药治疗策略的临床试验结果（表1）。Revumenib是首个获得美国食品药品监督管理局（FDA）批准的menin抑制剂，在复发/难治性KMT2A重排（R/R KMT2Ar）急性白血病（AL）患者中显示出64%（62/97）的总缓解率（ORR）和23%（22/97）的完全缓解（CR）+完全缓解伴部分血液学恢复（CRh）率，其中61%（11/18）的CR+CRh缓解者达到微小残留病（MRD）阴性（NCT04065399）。分别有15%（17/116）和13%（15/116）的患者出现≥3级分化综合征（DS）和QTc间期延长。Revumenib还评估用于MRD复发的急性髓系白血病（AML）患者的治疗，相关研究由Loo等人报告（ACTRN12621000439842）。对于NPM1突变（NPM1m）患者，36%的患者达到MRD阴性。Bleximenib单药用于存在KMT2Ar、NPM1m或NUP98/NUP214重排的R/R AL患者（NCT04811560），并确定了推荐的2期剂量（RP2D）。在RP2D下，ORR为48%（CR+CRh率为33%），中位至首次缓解时间为1.4个月。14%（21/146）的患者出现DS，其中2例因DS死亡。未观察到QTc间期延长。Enzomenib单药用于存在KMT2Ar或NPM1m的R/R AL患者，ORR达到57%（CR+CRh率为23%）。未观察到治疗相关QTc间期延长，也未出现因DS导致的死亡。值得注意的是，一名携带CALM-AF10融合（一种menin敏感性改变）的患者达到CR。此外，Wu等人报道了BN104单药在存在KMT2Ar、NPM1m和NUP98重排的R/R AML患者中的初步结果（NCT06052813）。在剂量递增阶段，ORR和CR+CRh率分别为89%（8/9）和33%（3/9），未观察到≥3级DS和QTc间期延长。尽管这些menin抑制剂作为单药治疗在R/R患者中显示出较高的缓解率，但≥3级不良事件也很常见，包括恶心、呕吐、发热性中性粒细胞减少症和腹泻。表1总结了所有不良事件的发生率，并提供了更多详细信息。Menin抑制剂联合疗法由于在临床前研究中观察到menin抑制剂与BCL2抑制剂和FLT3抑制剂具有协同作用，因此联合疗法为更好的治疗反应提供了临床潜力。相关的临床试验及其关键结果见表2。在R/R AML患者中，menin抑制剂、维奈克拉和去甲基化药物的联合疗法有所报道。Revumenib、ASTX727（口服地西他滨/cedazuridine）和维奈克拉的全口服联合方案获得82%（27/33）的ORR和48%（16/33）的CR/CRh率，至首次形态学缓解的中位时间仅有28天。在达到ORR和CR+CRh的患者中，分别有65%（17/26）和88%（14/16）的患者达到MRD阴性。≥3级DS和QTc间期延长发生率分别为3%（1/33）和9%（3/33）。与此同时，ziftomenib联合维奈克拉和阿扎胞苷（NCT05735184）在KMT2Ar/ NPM1m患者中也获得50%（24/48）的ORR和25%（12/48）的CR/CRh率，且未观察到ziftomenib相关QTc间期延长。尽管这两种方案在携带特定遗传改变的R/R AML亚群中显示出有希望的疗效，但两试验中均观察到骨髓抑制，强调了进一步探索最佳给药计划和剂量策略的必要性。基于在R/R AML患者中观察到的良好疗效，几项试验正在探索menin抑制剂联合疗法用于新诊断AML患者。Bleximenib联合强化疗（“7+3”方案）在NPM1m/KMT2Ar患者（NCT05453903）中显示出95%（20/21）的ORR和81%（17/21）的CR/CRh，且未观察到QTc间期延长和DS。Ziftomenib联合“7 + 3”方案在KMT2Ar/NPM1m患者（NCT05735184）中报告了91%（42/46）的ORR和CR/CRh率。在CRc患者中，200 mg ziftomenib剂量下81%（13/16）的患者达到MRD阴性，400 mg剂量下为75%（9/12），600 mg剂量下为67%（6/9）。该联合方案显示出与单独使用“7+3”相似的安全性特征，且在任何剂量水平下均未观察到ziftomenib相关QTc间期延长。2%（1/51）的患者观察到3级DS，但可控。卓越的缓解率和可管理的疗效支持menin抑制剂联合“7+3”方案作为KMT2Ar/NPM1m AML患者有前景的一线治疗方案。在使用联合疗法的四项临床试验中观察到的最常见不良事件主要包括骨髓抑制和胃肠道反应。总之，2024 ASH年会报道的menin抑制剂结果提供了初步的安全性特征和有希望的缓解率，但仍需进一步评估以提供更有力的证据。在未来，menin抑制剂将作为更多联合疗法的一部分扩展到一线治疗，为具有不同共突变或其他特征的患者提供精准治疗方案。此外，将menin抑制剂作为异基因移植后的维持治疗、MRD为导向的治疗以及可能在其他血液系统恶性肿瘤中的有价值选择，也正在积极探索中。Menin抑制剂的时代正在到来。参考文献Cao, G., Zhang, H., Sun, S. et al. Menin inhibitors from monotherapies to combination therapies: clinical trial updates from 2024 ASH annual meeting. J Hematol Oncol 18, 63 (2025). https://doi-org.ctust.aliya.filescenter.top/10.1186/s13045-025-01718-x声明：本文由“肿瘤界”整理与汇编，欢迎分享转载，如需使用本文内容，请务必注明出处。来源：聊聊血液原标题：【JHO】(IF=40.4)主鸿鹄教授团队总结Menin抑制剂单药或联合疗法的最新数据：2024ASH年会临床试验更新编辑：lagertha审核：南星

临床结果

2025-04-14

·Pharmaindustrial

SMPA and NCI Collaborate to Expand Potential of Enzomenib in Precision Oncology

Sumitomo Pharma America, Inc. has announced that it has entered into a Cooperative Research and Development Agreement (CRADA) with the National Cancer Institute (NCI), part of the US National Institutes of Health (NIH), to evaluate enzomenib, an investigational, oral, small molecule designed to inhibit the menin and KMT2A protein interaction present in certain difficult to treat cancers. This unique partnership aims to harness the combined expertise of SMPA and the NCI to further expand the scientific evaluation of enzomenib as a potential therapeutic and explore additional cancers to address unmet patient needs. Enzomenib is an investigational, oral, small-molecule currently being clinically evaluated by SMPA in Phase 1/2 clinical trials for relapsed or refractory acute leukemia. Enzomenib is designed to target the menin and mixed-lineage leukemia protein interaction, a key interaction for acute leukemia and other cancer cell growth. In preclinical studies, enzomenib demonstrated selective growth inhibition in human acute leukemia cell lines with KMT2A (MLL) rearrangements or NPM1 mutations – cancers with particularly high mortality rates and limited treatment options. "We are highly encouraged by the preliminary data showing promising clinical activity of enzomenib in patients with relapsed/refractory acute leukemia, and with the support and partnership of the National Cancer Institute, we are poised to continue this positive momentum by expanding exploration of its application across additional cancers," said Jatin Shah, M.D., Chief Medical Officer, Oncology, SMPA. "We're honored to partner with the National Cancer Institute whose scientific expertise, resources and commitment to advancing oncological research will enable an even broader pursuit of scientific innovation on behalf of patients with urgent and unmet needs," added Shah. As part of the collaboration, enzomenib will be explored in MyeloMATCH (Myeloid Malignancies Molecular Analysis for Therapy Choice), an NCI precision medicine clinical trial designed to improve treatment outcomes for individuals diagnosed with acute myeloid leukemia (AML) or myelodysplastic syndromes (MDS). Enzomenib will also be explored with other important NCI programs.

临床1期AACR会议

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	西班牙	Sumitomo Pharma America, Inc.	2022-02-28
急性淋巴细胞白血病	临床2期	中国台湾	Sumitomo Pharma America, Inc.	2022-02-28
急性淋巴细胞白血病	临床2期	英国	Sumitomo Pharma America, Inc.	2022-02-28

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适应症

分期

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


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)	醖襯廠鹽積鹽遞窪鬱顧(憲蓋製簾糧齋積廠遞窪) = None 憲鏇築積淵壓範夢餘鹽 (簾餘窪築餘憲觸選衊範 ) 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	鹽膚獵衊構憲積憲製壓(鑰憲觸齋壓醖鑰獵廠範) = 簾廠獵窪餘壓齋選壓鑰膚夢網蓋夢衊憲憲襯齋 (遞壓遞製餘顧夢觸構鑰 ) 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	憲獵夢憲蓋繭衊憲餘顧(蓋膚顧願壓壓壓艱鬱壓) = 壓醖蓋選積遞蓋築選網蓋鏇壓鏇醖鏇簾憲網鬱 (範願憲簾襯網網襯衊夢 ) 更多	积极	2023-12-10
				DSP-5336±concomitant azole therapy (NPM1c)	襯廠鬱膚積顧衊齋夢網(選鏇膚醖鏇齋遞願餘構) = 醖鬱鏇夢觸壓築糧鏇衊網繭蓋觸觸憲繭夢艱壓 (築艱築選積構鹽齋選襯 )