Delving into the Latest Updates on Ziftomenib with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

齐夫托美尼布, KO-381, KO-382

+ [4]

Target

MLL1 x menin

Action

inhibitors

Mechanism

MLL1 inhibitors(lysine methyltransferase 2A inhibitors), menin inhibitors(Menin inhibitors)

Therapeutic Areas

NeoplasmsHemic and Lymphatic DiseasesImmune System Diseases+ [3]

Active Indication

Acute myeloid leukemia with mutated NPM1Acute Myeloid LeukemiaAcute myeloid leukaemia with 11q23 abnormality+ [9]

Inactive Indication-

Originator Organization

Kura Oncology, Inc.

Active Organization

Kura Oncology, Inc.

Kyowa Kirin Co., Ltd.

Kura Ltd.Sti.

Inactive Organization-

License Organization

Kyowa Kirin Co., Ltd.

The University of Texas MD Anderson Cancer Center

Kura Oncology, Inc.

Drug Highest PhaseApproved

First Approval Date

United States (13 Nov 2025),

Acute myeloid leukemia with mutated NPM1

RegulationPriority Review (United States), Breakthrough Therapy (United States), Fast Track (United States), Orphan Drug (United States), Orphan Drug (European Union)

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Structure/Sequence

Molecular FormulaC33H42F3N9O2S2

InChIKeyBGGALFIXXQOTPY-NRFANRHFSA-N

CAS Registry2134675-36-6

This phase II trial tests how well ziftomenib works in treating patients with NPM1 mutated or KMT2A rearranged acute myeloid leukemia (AML) and are not eligible to receive standard therapy. AML is often due to genetic changes in the cancer cells, including mutations in the NPM1 gene and rearrangements involving the KMT2A gene. These mutations result in activation of the menin pathway. Menin is a type of protein in the body that helps to regulate some of the naturally occurring processes in the body, but can also be involved in some types of cancers. Ziftomenib blocks this menin pathway and may prevent the cancer cells from continuing to grow. Giving ziftomenib may kill more cancer cells in patients with NPM1 mutated or KMT2A rearranged AML that are not eligible to receive standard therapy.

Start Date01 Oct 2026

Sponsor / Collaborator

Ohio State University Comprehensive Cancer Center

[+1]

NCT07355335

/ Not yet recruitingPhase 1IIT

A Phase 1 Study of Menin-KMT2A Inhibitor Ziftomenib (KO-539) in Combination With Cereblon E3 Ligase Modulator Mezigdomide (CC-92480) in Adolescents and Adults With Relapsed or Refractory Acute Myeloid Leukemia (AML)

The purpose of this study is to evaluate the safety and tolerability of mezigdomide in combination with ziftomenib in adolescent and adult participants with either KMT2A-rearranged (KMT2A-r) or NPM1-mutant relapsed or refractory acute myeloid leukemia (AML).

Start Date09 Jul 2026

Sponsor / Collaborator

The Massachusetts General Hospital

[+2]

NCT07411586

/ Active, not recruitingPhase 1IIT

Phase 1/1b Trial Of Olutasidenib And Ziftomenib For NPM1 And IDH1 Co-Mutated Acute Myeloid Leukemia

The goal of Phase 1 is to find the recommended dose of ziftomenib and olutasidenib in patients with relapsed/refractory AML that has a mutation in the NPM1 and IDH1 genes.
The goal of Phase 1b is to learn if the recommended dose of ziftomenib and olutasidenib found in Phase 1 can help to control the disease.
The safety and effects of this combination will also be studied in both parts.

Start Date28 May 2026

Sponsor / Collaborator

The University of Texas MD Anderson Cancer Center

100 Clinical Results associated with Ziftomenib

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100 Translational Medicine associated with Ziftomenib

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100 Patents (Medical) associated with Ziftomenib

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53

Literatures (Medical) associated with Ziftomenib

04 Aug 2026·MOLECULAR CANCER THERAPEUTICS

Targeting Menin in T-lineage Acute Lymphoblastic Leukemia

Article

Author: Odenike, Olatoyosi ; DuVall, Adam S. ; Thirman, Michael J. ; Patel, Anand A. ; Karaoglu, Diren Arda ; Kessler, Linda ; Arnold, Olivia ; Cheng, Jason X. ; Dhar, Arjun ; Youshanlouei, Hamed R. ; Saygin, Caner ; Chan, Zachary ; Shimamoto, Kathryn ; Burrows, Francis ; Drazer, Michael W. ; Stock, Wendy ; Giordano, Giorgia

Abstract:

T-lineage acute lymphoblastic leukemia (T-ALL) lacks effective targeted therapies, with poor outcomes in relapsed/refractory (R/R) disease. HOXAhigh T-ALL is biologically aggressive and often resistant to standard therapy. Menin inhibitors, recently approved for KMT2A-rearranged leukemias, may be effective in T-ALL, but biomarkers of response remain undefined. This study aims to evaluate the efficacy of menin inhibition in T-ALL and identify molecular predictors of sensitivity. We tested menin inhibitors (ziftomenib, revumenib, and VTP50469) in 14 primary T-ALL samples and 8 cell lines, representing HOXAhigh and HOXAlow genotypes. In vitro sensitivity assays, xenograft mouse models, transcriptomics, proteomics, and phosphoproteomics were used to characterize drug response. MEF2C modulation experiments and combination studies with cyclin-dependent kinase (CDK) 1/2 and ERK1/2 inhibitors were performed in vitro and in vivo. Menin inhibitors suppressed leukemic growth in a subset of HOXAhigh and HOXAlow primary human T-ALL samples. Similarly, ziftomenib was effective in reducing tumor burden in xenografts without major toxicity. Upon treatment, we observed downregulation of canonical menin targets (HOXA, MEIS1, and MEF2C) and upregulation of T-cell differentiation programs. Phosphoproteomic studies identified MEF2C S222 phosphorylation—mediated by CDK1/2 and ERK1/2—as a predictor of ziftomenib sensitivity in T-ALL. MEF2C overexpression promoted proliferation and ziftomenib resistance, whereas its knockdown impaired growth. Ziftomenib synergized with CDK1/2 and ERK1/2 inhibitors in vitro and improved survival in xenografted mice. In conclusion, a subset of T-ALL, defined by high p-MEF2C S222, is sensitive to menin inhibition. Combining ziftomenib with CDK or ERK inhibition offers synergistic efficacy, supporting biomarker-driven clinical trials of this strategy in R/R T-ALL.

01 Aug 2026·Blood neoplasia

Menin inhibitors as a treatment for acute leukemia: from bench to the clinic

Review

Author: Cierpicki, Tomasz ; Madarang, Ellen ; Grembecka, Jolanta ; Watts, Justin

Menin inhibitors exploit the key biological mechanism behind KMT2A-rearranged (KMT2A-r) and nucleophosmin 1-mutated (NPM1-mut) leukemias by targeting the menin-KMT2A interaction and disrupting KMT2A/KMT2A fusion complexes binding to chromatin, thereby preventing transcriptional activation of fundamental leukemogenic programs (HOXA9/MEIS1). A series of remarkable discoveries, from the cloning and identification of the MLL1 (KMT2A) gene in 1991, to the first discovery of menin's role in leukemia in 2005, to the development of the first small-molecule menin inhibitor in 2012, and to the initiation of the first-in-human clinical trials in 2019, led to the US Food and Drug Administration (FDA) approval of the first menin inhibitor (revumenib) in 2024 for in the treatment of relapsed or refractory (R/R) KMT2A-r acute leukemia, representing a significant scientific achievement for the rapid clinical translation of molecularly targeted therapy. The menin inhibitors revumenib and ziftomenib have subsequently been FDA approved for R/R NPM1-mut acute myeloid leukemia (AML) in 2025, and at least 5 other menin inhibitors are in clinical development for leukemia. Here, we review the discovery, preclinical and clinical development, and safety and efficacy of menin inhibitors through 2025. Menin inhibitors hold promise as one of the most powerful single-agent targeted therapies in acute leukemia, with response rates of ∼50% or higher in R/R AML with KMT2A-r or NPM1-mut disease. Despite this notable clinical activity, response duration to menin inhibitors remains short-lived for most patients, which has resulted in an explosion of combination therapy trials in both R/R and newly diagnosed AML, including intensive chemotherapy and nonintensive (venetoclax-based) approaches, as well as combinations with targeted therapies and novel differentiation therapies.

01 Jul 2026·EUROPEAN JOURNAL OF HAEMATOLOGY

Targeting the Menin– KMT2A Axis in Acute Leukemia: From Epigenetic Dependency to Clinical Translation

Review

Author: Santino Caserta ; Massimo Gentile ; Mamdouh Skafi ; Maria Eugenia Alvaro ; Virginia Olivito ; Francesco Mendicino ; Enrica Antonia Martino ; Ernesto Vigna ; Eugenio Lucia ; Caterina Labanca ; Fortunato Morabito ; Nicola Amodio ; Antonella Bruzzese

ABSTRACT:

Acute leukemias characterized by a shared epigenetic dependency on the menin–KMT2A axis rely on aberrant HOX‐driven transcriptional programs that sustain leukemic self‐renewal and impair differentiation. This dependency is most evident in KMT2A‐rearranged and NPM1‐mutated acute myeloid leukemia (AML), but also extends to other HOX‐dependent entities, including leukemias with NUP98 rearrangements and UBTF tandem duplications, broadening the therapeutic relevance of menin inhibition. Menin acts as a central scaffold within chromatin‐associated complexes that maintain expression of HOXA cluster genes and MEIS1, integrating signals from epigenetic regulators and lineage‐specific transcription factors. Disruption of the menin–KMT2A interaction results in transcriptional reprogramming, induction of differentiation, and loss of leukemic stem cell properties, providing a strong mechanistic rationale for therapeutic targeting. This review synthesizes current knowledge on the molecular basis of menin dependency, with emphasis on structural insights, transcriptional circuitry, and lineage plasticity. We critically evaluate the preclinical and clinical development of menin inhibitors, including revumenib, ziftomenib, bleximinib, and icovamenib, summarizing efficacy signals in relapsed/refractory disease, safety profiles, and emerging resistance mechanisms. Special attention is given to combination strategies with venetoclax, FLT3 inhibitors, chemotherapy, and epigenetic agents, which aim to enhance response durability and mitigate resistance. Finally, we discuss ongoing clinical trials, unresolved challenges in patient selection and sequencing, and future directions for integrating menin inhibition into precision‐based treatment paradigms for acute leukemia.

208

News (Medical) associated with Ziftomenib

01 Sep 2026

·www.globenewswire.com

Kura Oncology to Participate in Three Investor Conferences in September

SAN DIEGO, Sept. 01, 2026 (GLOBE NEWSWIRE) -- Kura Oncology, Inc. (Nasdaq: KURA), a biopharmaceutical company focused on precision medicines for the treatment of cancer, today announced that management will present at the following investor conferences: Wells Fargo Healthcare ConferenceSeptember 8, 20263:45 p.m. ET / 12:45 p.m. PT Cantor Global Healthcare ConferenceSeptember 9, 20269:10 a.m. ET / 6:10 a.m. PT Morgan Stanley Global Healthcare Conference September 16, 20267:45 a.m. ET / 4:45 a.m. PT Live audio webcasts will be available in the Investors section of Kura’s website at https://kuraoncology.com/, with archived replays available following all three events. About Kura Oncology Kura Oncology is a biopharmaceutical company committed to realizing the promise of precision medicines for the treatment of cancer. Kura’s pipeline of small molecule drug candidates is designed to target cancer signaling pathways and address high-need hematologic malignancies and solid tumors. Kura developed and is commercializing KOMZIFTI® (ziftomenib), the FDA-approved once-daily, oral menin inhibitor for the treatment of adults with relapsed or refractory NPM1-mutated acute myeloid leukemia, and continues to pioneer advancements in menin inhibition and farnesyl transferase inhibition. For additional information, please visit the Kura website at https://kuraoncology.com/ and follow us on X and LinkedIn. Kura Contact Investors and Media:Greg Mann858-987-4046gmann@kuraoncology.com

Drug Approval

01 Sep 2026

·www.biospace.com

Kura Oncology to Participate in Three Investor Conferences in September 2026

SAN DIEGO, Sept. 01, 2026 (GLOBE NEWSWIRE) -- Kura Oncology, Inc. (Nasdaq: KURA), a biopharmaceutical company focused on precision medicines for the treatment of cancer, today announced that management will present at the following investor conferences: Wells Fargo Healthcare Conference September 8, 2026 3:45 p.m. ET / 12:45 p.m. PT Cantor Global Healthcare Conference September 9, 2026 9:10 a.m. ET / 6:10 a.m. PT Morgan Stanley Global Healthcare Conference September 16, 2026 7:45 a.m. ET / 4:45 a.m. PT Live audio webcasts will be available in the Investors section of Kura’s website at , with archived replays available following all three events. About Kura Oncology Kura Oncology is a biopharmaceutical company committed to realizing the promise of precision medicines for the treatment of cancer. Kura’s pipeline of small molecule drug candidates is designed to target cancer signaling pathways and address high-need hematologic malignancies and solid tumors. Kura developed and is commercializing KOMZIFTI® (ziftomenib), the FDA-approved once-daily, oral menin inhibitor for the treatment of adults with relapsed or refractory NPM1 -mutated acute myeloid leukemia, and continues to pioneer advancements in menin inhibition and farnesyl transferase inhibition. For additional information, please visit the Kura website at and follow us on X and LinkedIn . Kura Contact Investors and Media: Greg Mann 858-987-4046 gmann@kuraoncology.com

18 Aug 2026

·allsci.com

Dana-Farber wins NCI leukemia SPORE to tackle resistance across emerging AML drug classes

Dana-Farber Cancer Institute has received USD 2.43 million in first-year funding from the National Cancer Institute (NCI) for a new five-year Specialized Program of Research Excellence (SPORE) focused on translational research in myeloid leukemia. The multi-project P50 center encompasses three translational research programs, each incorporating planned clinical testing. Principal investigators Andrew A. Lane and Richard M. Stone lead the program, which is anchored within the Dana-Farber/Harvard Cancer Center (DF/HCC) and supported by three shared cores covering biospecimen banking, functional precision medicine, and computational biology. Each project targets a distinct vulnerability in AML biology. Project 1 investigates resistance mechanisms to menin inhibitors — a class that has drawn substantial industry interest following clinical validation in NPM1-mutant and KMT2A-rearranged AML — and proposes combining them with immunomodulatory imide drugs (IMiDs) in a clinical trial. Project 2 examines PI3 kinase gamma (PI3Kγ) inhibition as a therapeutic strategy, using mechanistic analyses to guide combination regimens and an early-phase trial to assess clinical activity. Project 3 focuses on the mammalian SWI/SNF (mSWI/SNF) chromatin remodeling complex, specifically pharmacologic inhibition of SMARCA4/2 ATPase activity, with a Phase Ib trial planned to evaluate combinations in AML patients. The mSWI/SNF complex has emerged as a drug target across multiple cancers. Foghorn Therapeutics previously evaluated dual SMARCA4/SMARCA2 ATPase inhibitor FHD-286 in a Phase I study in advanced myeloid malignancies, while its current clinical-stage FHD-909 program selectively targets SMARCA2 in SMARCA4-mutant solid tumors. Menin inhibition is further advanced, with Syndax Pharmaceuticals' revumenib approved in the US for KMT2A-rearranged acute leukemia and NPM1-mutant AML, and Kura Oncology's ziftomenib approved for NPM1-mutant AML. The SPORE program is designed to accelerate bidirectional translation between laboratory and clinical research, making the planned early-phase studies central to the new leukemia program rather than downstream objectives. Access the AllSci platform to explore the science behind the news. Spot something wrong? Report an issue with this article

Phase 1Drug ApprovalPhase 2

100 Deals associated with Ziftomenib

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External Link

KEGG	Wiki	ATC	Drug Bank
D12419	-	-	-

R&D Status

Approved

10 top approved records.

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Indication	Country/Location	Organization	Date
Acute myeloid leukemia with mutated NPM1	United States	Kura Oncology, Inc.	13 Nov 2025
Acute myeloid leukemia with mutated NPM1	United States	Kura Ltd.Sti.	13 Nov 2025

Developing

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Acute Myeloid Leukemia	Phase 3	Australia	Kura Oncology, Inc.	26 Sep 2025
Acute Myeloid Leukemia	Phase 3	Belgium	Kura Oncology, Inc.	26 Sep 2025
Acute Myeloid Leukemia	Phase 3	Canada	Kura Oncology, Inc.	26 Sep 2025
Acute Myeloid Leukemia	Phase 3	Czechia	Kura Oncology, Inc.	26 Sep 2025
Acute Myeloid Leukemia	Phase 3	France	Kura Oncology, Inc.	26 Sep 2025
Acute Myeloid Leukemia	Phase 3	Germany	Kura Oncology, Inc.	26 Sep 2025
Acute Myeloid Leukemia	Phase 3	Greece	Kura Oncology, Inc.	26 Sep 2025
Acute Myeloid Leukemia	Phase 3	Italy	Kura Oncology, Inc.	26 Sep 2025
Acute Myeloid Leukemia	Phase 3	Philippines	Kura Oncology, Inc.	26 Sep 2025
Acute Myeloid Leukemia	Phase 3	Poland	Kura Oncology, Inc.	26 Sep 2025

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT07007312 (KOMET-017, EHA2026)	Phase 3	Acute myeloid leukaemia with 11q23 abnormality \| Acute myeloid leukemia with mutated NPM1 First line NPM1 mutations \| KMT2A rearrangements	351	ziftomenib during 7+3 induction and cytarabine consolidation, and placebo during maintenance	rwcpasaaog(dmyyhrcpbc) = qylltwwyln jzjzikciol (esxhymlfxm ) View more	Positive	12 May 2026
NCT05735184 (KOMET-007, ASH2025)	Phase 1	Acute myeloid leukemia with mutated NPM1 NPM1-mutation	39	AzacitidineVenetoclax 600 mg + AzacitidineVenetoclax + AzacitidineVenetoclaxe (Newly diagnosed NPM1-m AML)	avizlcyglq(mpxhzgzxxm) = wcxjmiwdch xdjdtjucvk (hcfbdspixo ) View more	Positive	06 Dec 2025
NCT04067336 (KOMET-001, Pubmed \| J Clin Oncol)	Phase 1/2	Acute myeloid leukemia with mutated NPM1 NPM1-mutated	92	Ziftomenib 600 mg	hkeivbyfyp(bvzalthfgi) = sxsjuxcxby wmzfzntwoi (ebwnfvdxpf, 14 - 32) View more	Positive	01 Nov 2025
NCT04067336 (KOMET-001, ASCO2025) Manual	Phase 1/2	Acute myeloid leukemia with mutated NPM1 NPM1 Mutation	112	Ziftomenib 600 mg QDZiftomenib 600 mg QD (Phase 1b/2)	wdarmaoisn(gvfxofvywe) = zjjbwlqgbc qxvvvpahxw (ylthawiack, 17 - 34) View more	Positive	30 May 2025
NCT04067336 (KOMET-001, ASCO2025) Manual	Phase 1/2	Acute myeloid leukemia with mutated NPM1 NPM1 Mutation	112	Ziftomenib 600 mg QDZiftomenib 600 mg QD (Phase 2)	wdarmaoisn(gvfxofvywe) = ymedkkhqta qxvvvpahxw (ylthawiack, 15 - 33)	Positive	30 May 2025
NCT04067336 (KOMET-001, EHA2025)	Phase 1/2	Acute myeloid leukemia with mutated NPM1 NPM1-mutant	112	Ziftomenib 600 mg QD	yjwzzkibuk(ufrjngcpgl) = kihncktcbb nbgsqtwvrq (qpayifujsd, 17 - 34) View more	Positive	22 May 2025
NCT05735184 (KOMET-007, EHA2025)	Phase 1	Acute myeloid leukaemia with 11q23 abnormality \| Acute myeloid leukemia with mutated NPM1 NPM1-m \| KMT2A-r	51	Ziftomenib 600 mg QD + 7+3 induction	nuuubtdtkf(bjldwxvhit) = febrile neutropenia (47%), decreased platelet count (31%), anemia (22%), decreased neutrophil count (20%), decreased white blood cell count (16%) gkvevfsvpz (ojpoaecgbw ) View more	Positive	14 May 2025
NCT04067336 (KOMET-001, Company_Website) Manual	Phase 1/2	Acute Myeloid Leukemia NPM1 Mutation	-	Ziftomenib	mgcuufdnwl(fdmaxfusua) = The KOMET-001 trial achieved its primary endpoint of CR plus CR with partial hematological recovery (CRh) and the primary endpoint was statistically significant. nydexuhfrd (pznvbqzzqi ) Met View more	Positive	07 Feb 2025
KOMET-007 (GlobeNewswire) Manual	Phase 1	Acute myeloid leukemia with mutated NPM1 \| Acute Leukemia with a KMT2A Translocation First line NPM1 Mutation \| KMT2A Rearrangement	54	ziftomenib +venetoclax/azacitidine	gxtpjpvcfd(lpssxzqytg) = ckcysiicuz pdzwhoecnz (dpaecbsqnp ) View more	Positive	09 Dec 2024
KOMET-007 (GlobeNewswire) Manual	Phase 1		54	Ziftomenib+cytarabinecytarabine/daunorubicindaunorubicin	gxtpjpvcfd(lpssxzqytg) = gelrjclrvj pdzwhoecnz (dpaecbsqnp ) View more	Positive	09 Dec 2024
ASH2024	Not Applicable	-	-	Ziftomenib 200 mg	jqwkuuiyhn(rcyogpjtst) = ytwtydrwvl udepwwazqg (gechzbqnxy ) View more	-	08 Dec 2024
ASH2024	Not Applicable	-	-	Ziftomenib 400 mg	jqwkuuiyhn(rcyogpjtst) = jlucuogalm udepwwazqg (gechzbqnxy ) View more	-	08 Dec 2024
ASH2024	Not Applicable	-	-	Ziftomenib 200 mg	ddtgqclcjs(eblorbzfwj) = ltcphixjks ztinksuhkv (mnhunztwyn )	-	07 Dec 2024
ASH2024	Not Applicable	-	-	Ziftomenib 400 mg	ddtgqclcjs(eblorbzfwj) = xyufhcemzw ztinksuhkv (mnhunztwyn )	-	07 Dec 2024