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Menin inhibitor

CompoundAZD3632

Area under investigation

AML/MDS

Scientific PillarEpigenetics

 

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MOMENTUM trial overview

Tumor

AML/MDS with KMT2Ar, NPM1m, or other genotypes associated with HOX overexpression

Trial Identifier

NCT07155226

Phase

I/II

Regimen

AZD3632 (module 1), AZD3632 + posaconazole (Module 2)

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ALLight trial overview

MOMENTUM trial overview

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Target Overview

Prognosis of acute leukemias with rearrangements in the MLL1 (KMT2A) gene is poor (5-year OS <25%). MLL-rearrangements (MLL-r) account for 80% of infant ALL and 5-15% of children and adults with acute leukemias. Mutated nucleophosmin 1 gene (NPM1), known as NPM1c, occurs in up to 30% of AML patients. NPM1c adult patients achieve high response rates 80-90%, however 37-50% eventually relapse. mOS in R/R NPM1c patients poor: 2nd line 7.8 mo, 3rd line 5.4 mo, 4th line 3.5 mo. Menin mediates pro-leukemic gene expression in acute leukemias & high risk MDS with genetic alterations in KMT2A, NPM1, or other loci promoting HOX gene over-expression.1,2

Compound Overview

AZD3632 is a next-generation small-molecule that binds to the protein menin and blocks its interaction with the protein KMT2A, thereby suppressing pro-leukemic gene expression in acute leukemias and high-risk myelodysplastic syndromes with specific genetic alterations, including KMT2A gene rearrangements (KMT2Ar) and NPM1 gene mutations (NPM1m).1,3

AZD3632 is being evaluated in a Phase I clinical study of participants with advanced haematologic malignancies harboring KMT2Ar, NPM1m, or other genotypes associated with homeobox (HOX) gene overexpression.

Mechanism of Action

  • Mechanism of Action

References

1. Issa GC, et al. Leukemia. 2021;35(9):2482–2495. 2. Döhner H, Weisdorf DJ, Bloomfield CD. New England Journal of Medicine. 2015;373(12):1136-1152. 3. Bruin G, et al. Abstract presented at: ACS; August 26, 2026; Chicago, Illinois. Abs 4525231.

 

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MOMENTUM trial overview

Tumor

AML/MDS with KMT2Ar, NPM1m, or other genotypes associated with HOX overexpression

Trial Identifier

NCT07155226

Phase

I/II

Regimen

AZD3632 (module 1), AZD3632 + posaconazole (Module 2)

Visit ct.gov

ALLight trial overview

MOMENTUM trial overview

Take me to ClinicalTrials.Gov

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Abbreviations

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  • ALL

    Acute lymphoblastic leukemia

  • AML

    Acute myeloid leukemia

  • HOX

    Homeobox

  • KMT2A

    Lysine methyltransferase 2A; formerly MLL1

  • KMT2Ar / MLL-r

    KMT2A rearrangement / MLL rearrangement

  • MDS

    Myelodysplastic syndromes

  • mOS

    Median overall survival

  • mo

    Months

  • NPM1

    Nucleophosmin 1

  • NPM1c

    Cytoplasmic NPM1 mutant

  • NPM1m

    NPM1 mutation

  • OS

    Overall survival

  • R/R

    Relapsed/refractory

Some compounds herein refer to selected AstraZeneca pipeline products still under development. AstraZeneca pipeline products are investigational products and, as such, are not approved by the US Food & Drug Administration (FDA), the European Medicines Agency (EMA) or any other regulatory agency for the uses under investigation. Information regarding these investigational products should, under no circumstances, be regarded as a recommendation for their use or of their safety or efficacy.

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Veeva ID: Z4-84958 US-109129 DE-92568 Last Updated October 20263/26
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