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    DRUG:

    Revuforj (revumenib)

    i
    Other names: SNDX-5613, SNDX5613, SNDX 5613
    Company:
    Syndax Pharma
    Drug class:
    Menin-MLL inhibitor
    Related drugs:
    4d
    A Study to Find the Highest Dose of SNDX-5613 (Revumenib) as a Treatment Option After Hematopoietic Stem Cell Transplant in Children With Acute Lymphoblastic Leukemia, Acute Myeloid Leukemia, and Mixed Phenotype Acute Leukemia (clinicaltrials.gov)
    P1, N=29, Not yet recruiting, Children's Oncology Group
    New P1 trial
    |
    KMT2A (Lysine Methyltransferase 2A) • NUP98 (Nucleoporin 98 And 96 Precursor 2) • CD4 (CD4 Molecule)
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    KMT2A rearrangement
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    cytarabine • methotrexate • Revuforj (revumenib) • Starasid (cytarabine ocfosfate)
    4d
    Targeted Therapy in Acute Myeloid Leukemia: Current Approaches and Novel Directions. (PubMed, J Pers Med)
    Here, we detail the current targeted therapies available for AML: specifically, those targeting the BCL2 family (venetoclax), FLT3 (midostaurin, gilteritinib, quizartinib), IDH1/2 (enasidenib, ivosidenib), and MENIN (revumenib, ziftomenib). In addition, we outline potential mechanisms of resistance against these therapies, as well as efforts being taken to prevent or bypass them.
    Review • Journal • IO biomarker
    |
    FLT3 (Fms-related tyrosine kinase 3) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • BCL2 (B-cell CLL/lymphoma 2) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2)
    |
    Venclexta (venetoclax) • Xospata (gilteritinib) • midostaurin • Vanflyta (quizartinib) • Tibsovo (ivosidenib) • Revuforj (revumenib) • Idhifa (enasidenib) • Komzifti (ziftomenib)
    7d
    Revumenib in Combination With 7+3 + Midostaurin in AML (clinicaltrials.gov)
    P1, N=22, Recruiting, Richard Stone, MD | Trial completion date: Mar 2027 --> Mar 2028 | Trial primary completion date: Mar 2026 --> Mar 2027
    Trial completion date • Trial primary completion date
    |
    TP53 (Tumor protein P53) • FLT3 (Fms-related tyrosine kinase 3) • ABL1 (ABL proto-oncogene 1) • NPM1 (Nucleophosmin 1) • DNMT3A (DNA methyltransferase 1) • RUNX1 (RUNX Family Transcription Factor 1) • SF3B1 (Splicing Factor 3b Subunit 1) • ASXL1 (ASXL Transcriptional Regulator 1) • KMT2A (Lysine Methyltransferase 2A) • SRSF2 (Serine and arginine rich splicing factor 2) • CREBBP (CREB binding protein) • BCOR (BCL6 Corepressor) • U2AF1 (U2 Small Nuclear RNA Auxiliary Factor 1) • STAG2 (Stromal Antigen 2) • MECOM (MDS1 And EVI1 Complex Locus) • NUP214 (Nucleoporin 214) • GATA2 (GATA Binding Protein 2) • KAT6A (Lysine Acetyltransferase 6A) • ZRSR2 (Zinc Finger CCCH-Type, RNA Binding Motif And Serine/Arginine Rich 2)
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    TP53 mutation • FLT3-ITD mutation • NPM1 mutation • Chr del(5q)
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    midostaurin • daunorubicin • Revuforj (revumenib)
    7d
    REVEAL-ND NPM1: Study of Revumenib in Combination With Intensive Chemotherapy in Newly Diagnosed Acute Myeloid Leukemia (AML) With a NPM1 Mutation (clinicaltrials.gov)
    P3, N=468, Recruiting, Syndax Pharmaceuticals
    Trial initiation date
    |
    NPM1 (Nucleophosmin 1)
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    NPM1 mutation
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    cytarabine • Revuforj (revumenib)
    12d
    Discovery and preclinical activity of the menin-KMT2A inhibitor ziftomenib in acute leukemia models. (PubMed, Blood)
    We next assessed ziftomenib against four MEN1 (gene encoding menin) mutants (T349M, M327I, G331R, G331D) associated with clinical resistance to another menin inhibitor revumenib. The crystal structures of ziftomenib in complex with menin wild-type, T349M or G331R mutants revealed a similar binding mode of ziftomenib to these menin variants, rationalizing potent inhibitory activity towards these mutants. Ziftomenib has recently received FDA approval for adult patients with NPM1-mutated acute myeloid leukemia and continues to be evaluated clinically in leukemias with NPM1 or KMT2A alterations, both as monotherapy and in combinations.
    Preclinical • Journal
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    NPM1 (Nucleophosmin 1) • KMT2A (Lysine Methyltransferase 2A) • NUP98 (Nucleoporin 98 And 96 Precursor 2) • HOXA9 (Homeobox A9) • MEIS1 (Meis Homeobox 1) • MEN1 (Menin 1) • HOXB2 (Homeobox B2)
    |
    NPM1 mutation • KMT2A rearrangement
    |
    Revuforj (revumenib) • Komzifti (ziftomenib)
    14d
    AUGMENT-101: A Study of Revumenib in R/R Leukemias Including Those With an MLL/KMT2A Gene Rearrangement or NPM1 Mutation (clinicaltrials.gov)
    P1/2, N=447, Recruiting, Syndax Pharmaceuticals | N=67 --> 447
    Enrollment change
    |
    NPM1 (Nucleophosmin 1) • KMT2A (Lysine Methyltransferase 2A) • NUP98 (Nucleoporin 98 And 96 Precursor 2)
    |
    NPM1 mutation • KMT2A rearrangement
    |
    Revuforj (revumenib) • Tybost (cobicistat)
    19d
    OSU-23199: SNDX-5613 and Gilteritinib for the Treatment of Relapsed or Refractory FLT3-Mutated Acute Myeloid Leukemia and Concurrent MLL-Rearrangement or NPM1 Mutation (clinicaltrials.gov)
    P1, N=30, Recruiting, Uma Borate | Trial completion date: Dec 2025 --> Feb 2027 | Trial primary completion date: Dec 2025 --> Jan 2027
    Trial completion date • Trial primary completion date
    |
    FLT3 (Fms-related tyrosine kinase 3) • NPM1 (Nucleophosmin 1) • KMT2A (Lysine Methyltransferase 2A) • NUP98 (Nucleoporin 98 And 96 Precursor 2) • MEIS1 (Meis Homeobox 1)
    |
    FLT3 mutation • NPM1 mutation • MLL mutation
    |
    Xospata (gilteritinib) • Revuforj (revumenib)
    20d
    Immunophenotypic changes following menin inhibition in acute myeloid leukemia. (PubMed, Leukemia)
    Morphologic remission with undetectable measurable residual disease (MRD) by flow cytometry following revumenib was associated with improved overall survival, with a median of 23.6 months compared with 20.8 months in patients with morphologic response and detectable MRD, and 3.2 months in non-responders. In summary, treatment monitoring of AML by flow cytometry, following menin inhibition, requires recognition of phenotypic changes associated with differentiation.
    Journal
    |
    NPM1 (Nucleophosmin 1) • KMT2A (Lysine Methyltransferase 2A)
    |
    NPM1 mutation • KMT2A mutation
    |
    Revuforj (revumenib)
    23d
    Clinical Integration of Menin Inhibitors in AML: Evolving Data and Therapeutic Perspectives. (PubMed, Oncol Res)
    This manuscript reviews the molecular rationale of menin inhibition for aberrant homeobox/myeloid ectopic insertion site 1 (HOX/MEIS1)-driven gene expression and leukemogenesis, clinical trial outcomes, and safety data for menin inhibitors, with a focus on recently FDA-approved revumenib and several other agents in development, ziftomenib (KO-539), bleximenib (JNJ-75276617), and icovamenib (BMF-219). We also focused our discussion on future directions to include resistance mechanisms, biomarker identification and monitoring strategies, and combination therapies. Menin inhibition is now being clinically integrated into relapsed/refractory and frontline treatment settings.
    Review • Journal
    |
    NPM1 (Nucleophosmin 1) • KMT2A (Lysine Methyltransferase 2A) • MEIS1 (Meis Homeobox 1)
    |
    NPM1 mutation • KMT2A rearrangement
    |
    Revuforj (revumenib) • Komzifti (ziftomenib) • icovamenib (BMF-219) • bleximenib (JNJ-6617)
    25d
    CAR T cells derived from a novel, high-affinity anti-CLL-1 monoclonal antibody exhibit a significant anti-AML effect. (PubMed, Cancer Immunol Immunother)
    Additionally, treatment with revumenib, a menin inhibitor, increased CLL-1 expression in AML cells harboring mixed-lineage leukemia (MLL) fusion genes or the NPM1 mutation, making them more susceptible to 2-23 CAR T cell-mediated cytotoxicity in vitro. These findings suggest that the clinical efficacy of CAR T cells derived from the novel, high-affinity anti-CLL-1 mAb 2-23 should be tested in patients with CLL-1-positive AML and also that combining 2-23 CAR T cells with revumenib may benefit some patients with CLL-1low/- AML.
    Journal
    |
    NPM1 (Nucleophosmin 1)
    |
    NPM1 mutation
    |
    Revuforj (revumenib)
    28d
    A Phase Ia/Ib Trial of Revumenib Combined With Cytarabine, Daunorubicin, and Gemtuzumab Ozogamicin (GO) in Frontline and Relapsed /Refractory Pediatric Acute Leukemia Patients (clinicaltrials.gov)
    P1, N=32, Not yet recruiting, M.D. Anderson Cancer Center | Initiation date: Dec 2025 --> Dec 2027
    Trial initiation date
    |
    KMT2A (Lysine Methyltransferase 2A) • NUP98 (Nucleoporin 98 And 96 Precursor 2)
    |
    cytarabine • Mylotarg (gemtuzumab ozogamicin) • daunorubicin • Revuforj (revumenib)
    28d
    Targeting menin in T-lineage acute lymphoblastic leukemia. (PubMed, Mol Cancer Ther)
    We tested menin inhibitors (ziftomenib, revumenib, VTP-50469) in 14 primary T-ALL samples and 8 cell lines, representing HOXA-high and HOXA-low genotypes. 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 relapsed/refractory T-ALL.
    Journal
    |
    KMT2A (Lysine Methyltransferase 2A) • MEIS1 (Meis Homeobox 1) • CDK1 (Cyclin-dependent kinase 1) • MEF2C (Myocyte Enhancer Factor 2C)
    |
    Revuforj (revumenib) • Komzifti (ziftomenib) • VTP-50469