To date, this new class of drugs has been tested in phase I and II clinical trials, both alone and in combination with synergistic drugs showing promising results in terms of response rates and safety in heavily pre-treated acute leukemia patients. In this brief review, we summarize the key findings on menin inhibitors, focusing on the mechanism of action and preliminary clinical data on the treatment of acute myeloid leukemia with this promising new class of agents, particularly revumenib and ziftomenib.

11 days ago

Review • Journal

NPM1 (Nucleophosmin 1) • KMT2A (Lysine Methyltransferase 2A) • MEIS1 (Meis Homeobox 1)

NPM1 mutation • MLL rearrangement • KMT2A expression

revumenib (SNDX-5613) • ziftomenib (KO-539)

16d

Study of Revumenib, Azacitidine, and Venetoclax in Pediatric and Young Adult Patients With Refractory or Relapsed Acute Myeloid Leukemia (clinicaltrials.gov)

P1, N=24, Recruiting, St. Jude Children's Research Hospital | Not yet recruiting --> Recruiting

16 days ago

Enrollment open

Venclexta (venetoclax) • cytarabine • azacitidine • methotrexate • revumenib (SNDX-5613)

22d

Synergistic Effects of the RARalpha Agonist Tamibarotene and the Menin Inhibitor Revumenib in Acute Myeloid Leukemia Cells with KMT2A Rearrangement or NPM1 Mutation. (PubMed, Cancers (Basel))

The impact of revumenib on KMT2Ar or NPM1c AML cells was significantly enhanced when combined with tamibarotene, demonstrating synergistic differentiation or apoptosis initiation. These findings propose promising strategies for relapsed/refractory AML patients with defined molecular characteristics.

22 days ago

Journal

NPM1 (Nucleophosmin 1) • KMT2A (Lysine Methyltransferase 2A) • RARA (Retinoic Acid Receptor Alpha) • CDK6 (Cyclin-dependent kinase 6) • CEBPA (CCAAT Enhancer Binding Protein Alpha)

NPM1 mutation • KMT2A rearrangement • MLL rearrangement

revumenib (SNDX-5613) • Amnolake (tamibarotene)

A Study of SNDX-5613 in Combination With Intensive Chemotherapy in Participants With Acute Myeloid Leukemias (clinicaltrials.gov)

P1, N=76, Recruiting, Syndax Pharmaceuticals | Not yet recruiting --> Recruiting

1 month ago

Enrollment open • Combination therapy

cytarabine • revumenib (SNDX-5613)

2ms

A Study of SNDX-5613 in Combination With Chemotherapy for Patients Diagnosed With Relapsed or Refractory Leukemia (clinicaltrials.gov)

P2, N=78, Recruiting, Children's Oncology Group | Active, not recruiting --> Recruiting

2 months ago

Enrollment open • Combination therapy

KMT2A (Lysine Methyltransferase 2A)

MLL rearrangement

cytarabine • methotrexate • vincristine • revumenib (SNDX-5613) • fludarabine IV • Asparlas (calaspargase pegol-mknl) • Starasid (cytarabine ocfosfate)

2ms

Phase I Trial of Revumenib in Combination With 7+3+Midostaurin (clinicaltrials.gov)

P1, N=22, Not yet recruiting, Maximilian Stahl, MD

2 months ago

New P1 trial • Combination therapy

Rydapt (midostaurin) • daunorubicin • revumenib (SNDX-5613)

2ms

Testing the Addition of an Anti-cancer Drug, SNDX-5613, to the Standard Chemotherapy Treatment (Daunorubicin and Cytarabine) for Newly Diagnosed Patients With Acute Myeloid Leukemia That Has Changes in NPM1 or MLL/KMT2A Gene (clinicaltrials.gov)

P1, N=28, Recruiting, National Cancer Institute (NCI) | Not yet recruiting --> Recruiting | Trial completion date: Feb 2024 --> Dec 2027 | Initiation date: Feb 2024 --> Nov 2024 | Trial primary completion date: Feb 2024 --> Dec 2027

2 months ago

Enrollment open • Trial completion date • Trial initiation date • Trial primary completion date • Combination therapy

FLT3 (Fms-related tyrosine kinase 3) • NPM1 (Nucleophosmin 1) • KMT2A (Lysine Methyltransferase 2A)

FLT3-ITD mutation • FLT3 mutation • NPM1 mutation • MLL rearrangement • FLT3 wild-type • MLL mutation

daunorubicin • revumenib (SNDX-5613) • Starasid (cytarabine ocfosfate)

2ms

A Multi-Site Break Through Cancer Trial: Phase II Study Investigating Dual Inhibition of BCL2 and Menin in AML MRD Using the Combination of Venetoclax and Revumenib (clinicaltrials.gov)

P2, N=8, Not yet recruiting, M.D. Anderson Cancer Center

2 months ago

New P2 trial

Venclexta (venetoclax) • revumenib (SNDX-5613)

3ms

A Study of SNDX-5613 in Combination With Chemotherapy for Patients Diagnosed With Relapsed or Refractory Leukemia (clinicaltrials.gov)

P2, N=78, Active, not recruiting, Children's Oncology Group | Recruiting --> Active, not recruiting

3 months ago

Enrollment closed • Combination therapy

KMT2A (Lysine Methyltransferase 2A)

MLL rearrangement

cytarabine • methotrexate • vincristine • revumenib (SNDX-5613) • fludarabine IV • Asparlas (calaspargase pegol-mknl) • Starasid (cytarabine ocfosfate)

3ms

Small Molecule Menin Inhibitors: Novel Therapeutic Agents Targeting Acute Myeloid Leukemia with KMT2A Rearrangement or NPM1 Mutation. (PubMed, Oncol Ther)

Recent phase 1/2 clinical trials confirmed the efficacy of SNDX-5613 (revumenib) and KO-539 (ziftomenib) and their acceptable tolerability. Several small molecule menin inhibitors are currently being evaluated as a combination therapy with standard of care treatments. The current paper reviews the recent progress in exploring the inhibitors of menin-KMT2A interactions and their application prospects in the treatment of acute leukemias.

3 months ago

Review • Journal

NPM1 (Nucleophosmin 1) • KMT2A (Lysine Methyltransferase 2A)

NPM1 mutation • KMT2A rearrangement • MLL rearrangement

revumenib (SNDX-5613) • ziftomenib (KO-539)

3ms

A Phase II Study of the Menin Inhibitor Revumenib in Leukemia Associated With Upregulation of HOX Genes (clinicaltrials.gov)

P2, N=15, Not yet recruiting, M.D. Anderson Cancer Center

3 months ago

New P2 trial

revumenib (SNDX-5613)

3ms

A Study of SNDX-5613 in Combination With Intensive Chemotherapy in Participants With Acute Myeloid Leukemias (clinicaltrials.gov)

P1, N=76, Not yet recruiting, Syndax Pharmaceuticals

3 months ago

New P1 trial • Combination therapy

cytarabine • revumenib (SNDX-5613)

4ms

Evaluation of SNDX-5613 in Participants With Colorectal Cancer and Other Solid Tumors (clinicaltrials.gov)

P1/2, N=158, Recruiting, Syndax Pharmaceuticals | Trial completion date: Sep 2025 --> Aug 2027 | Trial primary completion date: Sep 2023 --> Dec 2024

4 months ago

Trial completion date • Trial primary completion date

Stivarga (regorafenib) • revumenib (SNDX-5613)

4ms

A Study of SNDX-5613 in Combination With Chemotherapy in Participants With R/R Acute Leukemia (clinicaltrials.gov)

P1, N=30, Active, not recruiting, Syndax Pharmaceuticals | Recruiting --> Active, not recruiting | N=54 --> 30

4 months ago

Enrollment closed • Enrollment change • Combination therapy

KMT2A (Lysine Methyltransferase 2A) • NUP98 (Nucleoporin 98 And 96 Precursor 2)

KMT2A rearrangement • MLL rearrangement

cytarabine • cyclophosphamide • revumenib (SNDX-5613)

5ms

Study of Revumenib, Azacitidine, and Venetoclax in Pediatric and Young Adult Patients With Refractory or Relapsed Acute Myeloid Leukemia (clinicaltrials.gov)

P1, N=24, Not yet recruiting, St. Jude Children's Research Hospital

5 months ago

New P1 trial

Venclexta (venetoclax) • cytarabine • azacitidine • methotrexate • revumenib (SNDX-5613)

5ms

P1, N=28, Not yet recruiting, National Cancer Institute (NCI) | Phase classification: P1b --> P1

5 months ago

Phase classification

FLT3 (Fms-related tyrosine kinase 3) • NPM1 (Nucleophosmin 1) • KMT2A (Lysine Methyltransferase 2A)

FLT3-ITD mutation • FLT3 mutation • NPM1 mutation • MLL rearrangement • FLT3 wild-type • MLL mutation

daunorubicin • revumenib (SNDX-5613) • Starasid (cytarabine ocfosfate)

5ms

Menin Inhibitors Trigger Leukemia Remissions. (PubMed, Cancer Discov)

A phase II study of revumenib yielded a response rate of 63% in patients with relapsed or refractory disease and KMT2A rearrangements; a phase I trial combining the drug with three chemotherapies also yielded complete remissions in patients with acute myeloid leukemia. A phase I study of a different menin inhibitor detected responses in 63% of patients with acute leukemia and certain gene alterations.

5 months ago

Journal

KMT2A (Lysine Methyltransferase 2A)

KMT2A rearrangement • MLL rearrangement

revumenib (SNDX-5613)

5ms

Phase 1/2 evaluation of revumenib in patients with advanced colorectal cancer and other solid tumors. (ASCO-GI 2024)

Patients with CRC must be unable to receive or have disease that progressed on oxaliplatin, irinotecan, and bevacizumab; if left-sided RAS wild-type CRC, the patient must have received anti–epidermal growth factor receptor therapy. As of September 5, 2023, 13 patients were enrolled in phase 1a of this study. Clinical trial information: NCT05731947.

5 months ago

Clinical • P1/2 data • Metastases

EGFR (Epidermal growth factor receptor) • ER (Estrogen receptor) • KMT2A (Lysine Methyltransferase 2A)

ER positive • RAS wild-type

Avastin (bevacizumab) • oxaliplatin • irinotecan • revumenib (SNDX-5613)

5ms

A Study of Revumenib in Combination With Chemotherapy for Patients Diagnosed With Relapsed or Refractory Leukemia (clinicaltrials.gov)

P2, N=78, Recruiting, Children's Oncology Group | Not yet recruiting --> Recruiting

5 months ago

Enrollment open • Combination therapy

KMT2A (Lysine Methyltransferase 2A)

MLL rearrangement

cytarabine • methotrexate • vincristine • revumenib (SNDX-5613) • Oncaspar liquid (pegaspargase) • fludarabine IV • Asparlas (calaspargase pegol-mknl) • Starasid (cytarabine ocfosfate)

5ms

The LSD1 Inhibitor Ory-1001 (ladademstat) in Combination with Menin Inhibitor SNDX-5613 (revumenib) Has Synergistic in Vitro Activity in KMT2A-Rearranged AML Models (ASH 2023)

LSD1 Inhibitor ladademstat in Combination with Menin Inhibitor revumenib has synergistic effect in KMT2A-Rearranged AML models. Surprisingly, we also found that PSIP1, which is essential for inducing MLL-rearranged leukemia, interacts with LSD1. This suggests that PSIP1 may modulate gene expression through its ability to interact with both MLL1 and LSD1.

5 months ago

Preclinical • Combination therapy

KMT2A (Lysine Methyltransferase 2A) • HDAC2 (Histone deacetylase 2) • HDAC1 (Histone Deacetylase 1)

KMT2A rearrangement • MLL rearrangement • KMT2A expression • MLL fusion

revumenib (SNDX-5613) • iadademstat (ORY-1001)

6ms

Revumenib Monotherapy in Patients with Relapsed/Refractory KMT2Ar Acute Leukemia: Topline Efficacy and Safety Results from the Pivotal Augment-101 Phase 2 Study (ASH 2023)

Rev demonstrated clinically meaningful results in a heavily pretreated KMT2Ar population, including high ORR and rates of MRD negativity and subsequent HSCT. At IA, this pivotal study met its primary endpoint and the KMT2Ar cohorts were stopped early for efficacy.

6 months ago

Clinical • P2 data • Late-breaking abstract

NPM1 (Nucleophosmin 1) • KMT2A (Lysine Methyltransferase 2A)

NPM1 mutation • MLL rearrangement • MLL fusion

revumenib (SNDX-5613)

6ms

Revumenib Maintenance Therapy Following Revumenib-Induced Remission and Transplant (ASH 2023)

With 3 patients on revumenib maintenance therapy for more than a year, long-term responses, including conversion to MRD-negative status, were seen in these heavily pretreated patients with AML. Resuming revumenib post HSCT had a tolerable safety profile consistent with that previously reported for the AUGMENT-101 study.

6 months ago

Clinical

NPM1 (Nucleophosmin 1) • KMT2A (Lysine Methyltransferase 2A) • NUP98 (Nucleoporin 98 And 96 Precursor 2)

NPM1 mutation • MLL rearrangement • NUP93 mutation

revumenib (SNDX-5613)

6ms

Notable Efficacy of Co-Treatment with FHD-286, a Dual BRG1/BRM ATP-Ase Inhibitor, and Menin or BET Inhibitor, Decitabine or Venetoclax Against AML with MLL-r or Mutant NPM1 (ASH 2023)

BRG1 (SMARCA4) and BRM (SMARCA2) are the core ATPase within the multi-protein, ATP-dependent, chromatin remodeling BAF complexes that regulate gene transcription. Finally, co-treatment with FHD-286 and OTX015 or SNDX-5613 (oral gavage) was significantly more effective than each drug alone in reducing the AML burden and overall survival of mice engrafted with a separate PDX model of AML cells with mtNPM1 and FLT3-ITD, without significant toxicity. These findings demonstrate the pre-clinical efficacy of FHD-286-based rational combinations and underscore their promise against AML with MLL1r or mtNPM1.

6 months ago

Clinical • PARP Biomarker • IO biomarker

FLT3 (Fms-related tyrosine kinase 3) • MYC (V-myc avian myelocytomatosis viral oncogene homolog) • BCL2 (B-cell CLL/lymphoma 2) • NPM1 (Nucleophosmin 1) • MCL1 (Myeloid cell leukemia 1) • SMARCA4 (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily A, member 4) • CDK4 (Cyclin-dependent kinase 4) • CD123 (Interleukin 3 Receptor Subunit Alpha) • CD33 (CD33 Molecule) • CEBPA (CCAAT Enhancer Binding Protein Alpha) • PLK1 (Polo Like Kinase 1) • CASP3 (Caspase 3) • ITGAM (Integrin, alpha M) • BRD4 (Bromodomain Containing 4) • IL3RA (Interleukin 3 Receptor Subunit Alpha) • CD99 (CD99 Molecule) • CDKN1A (Cyclin-dependent kinase inhibitor 1A) • HEXIM1 (HEXIM P-TEFb Complex Subunit 1) • MEF2C (Myocyte Enhancer Factor 2C) • SMARCA2 (SWI/SNF Related, Matrix Associated, Actin Dependent Regulator Of Chromatin, Subfamily A, Member 2) • CLEC12A (C-Type Lectin Domain Family 12 Member A) • PBX3 (PBX Homeobox 3)

FLT3 mutation • NPM1 mutation • CD123 expression

Venclexta (venetoclax) • decitabine • revumenib (SNDX-5613) • birabresib (OTX015) • FHD-286

6ms

Transcriptomic without Clinical Response to Menin Inhibition As a Mechanism of Upfront Resistance in Samples from Mutliply Relapsed Patients with KMT2A-Rearranged Leukemia (ASH 2023)

A transcriptomic response (i.e. downregulation of KMT2A-fusion target genes) without a clinical response was the most common pattern of upfront resistance in the recently reported phase I/II clinical trial of the Menin inhibitor revumenib. We conclude that it will be critical to use Menin-inhibitors upfront or in early lines of therapy before substantial clonal evolution has occurred.

6 months ago

Clinical • IO biomarker

TP53 (Tumor protein P53) • NPM1 (Nucleophosmin 1) • KMT2A (Lysine Methyltransferase 2A) • AFF1 (AF4/FMR2 Family Member 1) • MEN1 (Menin 1) • AFDN (Afadin, Adherens Junction Formation Factor) • MLLT10 (MLLT10 Histone Lysine Methyltransferase DOT1L Cofactor)

TP53 mutation • NPM1 mutation • RAS mutation • KMT2A rearrangement • MLL rearrangement • MLL fusion

revumenib (SNDX-5613)

6ms

Single-Cell Proteomic Analysis Reveals Menin Inhibition-Induced Proteomic Alterations in AML Patients Treated with Revumenib (ASH 2023)

In conclusion, multimodal sc analysis revealed profound proteomic alterations induced by revumenib and identified potential therapeutic targets. These findings present new avenues for optimizing combinatorial treatment regimens, enhancing revumenib's efficacy, and illuminating survival mechanisms in persistent, differentiated AML blasts.

6 months ago

Clinical • IO biomarker • Omic analysis

TP53 (Tumor protein P53) • KIT (KIT proto-oncogene, receptor tyrosine kinase) • BCL2 (B-cell CLL/lymphoma 2) • NPM1 (Nucleophosmin 1) • KMT2A (Lysine Methyltransferase 2A) • BCL2L1 (BCL2-like 1) • CD123 (Interleukin 3 Receptor Subunit Alpha) • CD34 (CD34 molecule) • CD14 (CD14 Molecule) • CD68 (CD68 Molecule) • ITGAM (Integrin, alpha M) • MEIS1 (Meis Homeobox 1) • IL3RA (Interleukin 3 Receptor Subunit Alpha) • PBX3 (PBX Homeobox 3)

NPM1 mutation • KMT2A rearrangement • MLL rearrangement • MCL1 expression • TP53 expression

revumenib (SNDX-5613)

6ms

Revumenib Monotherapy in Patients with Relapsed/Refractory KMT2Ar Acute Leukemias: Efficacy and Safety Results from the Augment-101 Phase 1/2 Study (ASH 2023)

These phase 1 data continue to demonstrate deep responses to revumenib and a manageable safety profile in heavily pretreated patients with R/R KMT2Ar acute leukemia across ages and subtypes. The lack of targeted therapies approved for KMT2Ar leukemia indicate the need for further investigation of novel, potentially transformative therapies such as revumenib. Enrollment in the AUGMENT-101 trial is ongoing.

6 months ago

Clinical • P1/2 data

NPM1 (Nucleophosmin 1) • KMT2A (Lysine Methyltransferase 2A)

NPM1 mutation • MLL rearrangement

revumenib (SNDX-5613)

6ms

Decoding the Epigenetic Drivers of Menin-MLL Inhibitor Resistance in KMT2A-Rearranged Acute Myeloid Leukemia (ASH 2023)

Consistent with our screen results, the depletion of PRC1.1 components led to a markedly increase in IC50 values when treated with the Menin inhibitor VTP50469 in both human and murine KMT2A-rearranged cell models...This is consistent with recent data from phase I clinical trial of revumenib (SNDX-5613) and preclinical patient derived xenograft models, wherein the Menin inhibitor persistently inhibited key KMT2A targets, even in resistant samples...In summary, our study identifies the non-canonical PRC1.1 as a key epigenetic driver of Menin-MLL resistance through a KMT2A target gene-independent mechanism which involves aberrant activation of MYC. We have further provided evidence that AML cells with loss of PRC1.1 are hypersensitive to BCL-2 inhibitor Venetoclax, opening a new therapeutic avenue for tackling Menin-resistant AMLs driven by polycomb inactivation.

6 months ago

IO biomarker

MYC (V-myc avian myelocytomatosis viral oncogene homolog) • NPM1 (Nucleophosmin 1) • KMT2A (Lysine Methyltransferase 2A) • BCOR (BCL6 Corepressor) • MEIS1 (Meis Homeobox 1) • MEF2C (Myocyte Enhancer Factor 2C) • PBX3 (PBX Homeobox 3) • SUZ12 (SUZ12 Polycomb Repressive Complex 2 Subunit)

NPM1 mutation • KMT2A rearrangement • MLL rearrangement • MYC expression • KMT2A rearrangement + NPM1 mutation

Venclexta (venetoclax) • revumenib (SNDX-5613) • VTP-50469

6ms

Early Results of the Phase I/II Study Investigating the All-Oral Combination of the Menin Inhibitor Revumenib (SNDX-5613) with Decitabine/Cedazuridine (ASTX727) and Venetoclax in Acute Myeloid Leukemia (SAVE) (ASH 2023)

ASTX727 (decitabine/ cedazuridine) was administered at 35 mg/100 mg PO daily days 1-5, venetoclax at 400 mg (target dose) PO daily days 1-14, and revumenib 113 mg PO Q12h (dose level [DL] 0) or 163 mg PO Q12h (DL 1, used in phase II monotherapy), days 1-28 with either posaconazole or voriconazole (strong CYP3A4 inhibitors, for antifungal prophylaxis). Early results indicate acceptable safety and high efficacy of this combination in R/R myeloid leukemias with either KMT2Ar or NPM1mt or NUP98r. This study is ongoing with plans to establish the recommended phase 2 dose and optimize delivery of this combination.

6 months ago

P1/2 data • IO biomarker

NPM1 (Nucleophosmin 1) • KMT2A (Lysine Methyltransferase 2A) • NUP98 (Nucleoporin 98 And 96 Precursor 2)

Venclexta (venetoclax) • revumenib (SNDX-5613) • Inqovi (decitabine/cedazuridine) • Noxafil (posaconazole)

6ms

AUGMENT-101: A Study of SNDX-5613 in R/R Leukemias Including Those With an MLLr/KMT2A Gene Rearrangement or NPM1 Mutation (clinicaltrials.gov)

P1/2, N=440, Recruiting, Syndax Pharmaceuticals | Trial completion date: Apr 2026 --> Dec 2024 | Trial primary completion date: Apr 2025 --> Dec 2024

6 months ago

Trial completion date • Trial primary completion date

KMT2A (Lysine Methyltransferase 2A) • NUP98 (Nucleoporin 98 And 96 Precursor 2)

NPM1 mutation • MLL rearrangement • MLL rearrangement

revumenib (SNDX-5613) • Tybost (cobicistat)

6ms

A Study of SNDX-5613 in Combination With Chemotherapy in Participants With R/R Acute Leukemia (clinicaltrials.gov)

P1, N=54, Recruiting, Syndax Pharmaceuticals | Trial completion date: Feb 2024 --> Jun 2024 | Trial primary completion date: Jul 2023 --> Apr 2024

6 months ago

Trial completion date • Trial primary completion date • Combination therapy

KMT2A (Lysine Methyltransferase 2A) • NUP98 (Nucleoporin 98 And 96 Precursor 2)

KMT2A rearrangement • MLL rearrangement

cytarabine • cyclophosphamide • revumenib (SNDX-5613)

6ms

A Phase 1B Study Assessing the Safety and Activity of SNDX-5613 (revumenib) in Combination with Age-Modified Chemotherapy in Newly Diagnosed patients with KMT2Ar acute lymphoblastic leukemia (ALL) or acute leukemia with ambiguous lineage (ALAL). (SWOG-Fall 2023)

No abstract available

6 months ago

Clinical • P1 data • Combination therapy

KMT2A (Lysine Methyltransferase 2A)

revumenib (SNDX-5613)

6ms

Acute myeloid leukemias with UBTF tandem duplications are sensitive to Menin inhibitors. (PubMed, Blood)

Finally, we demonstrate that primary cells from UBTF-TD leukemias are sensitive to the Menin inhibitor SNDX-5613, resulting in markedly reduced in vitro and in vivo tumor growth, myeloid differentiation, and abrogation of the UBTF-TD leukemic expression signature. These findings provide a viable therapeutic strategy for patients with this high-risk AML subtype.

6 months ago

Journal

NPM1 (Nucleophosmin 1) • KMT2A (Lysine Methyltransferase 2A) • NUP98 (Nucleoporin 98 And 96 Precursor 2) • CD34 (CD34 molecule) • MEIS1 (Meis Homeobox 1)

NPM1 mutation

revumenib (SNDX-5613)

6ms

P1b, N=28, Not yet recruiting, National Cancer Institute (NCI) | Initiation date: Jun 2023 --> Oct 2023

6 months ago

Trial initiation date • Combination therapy

FLT3 (Fms-related tyrosine kinase 3) • NPM1 (Nucleophosmin 1) • KMT2A (Lysine Methyltransferase 2A)

FLT3-ITD mutation • FLT3 mutation • NPM1 mutation • MLL rearrangement • FLT3 wild-type • MLL mutation

daunorubicin • revumenib (SNDX-5613) • Starasid (cytarabine ocfosfate)

9ms

A Study of Revumenib in Combination With Chemotherapy for Patients Diagnosed With Relapsed or Refractory Leukemia (clinicaltrials.gov)

P2, N=78, Not yet recruiting, Children's Oncology Group | Initiation date: Jun 2023 --> Oct 2023

9 months ago

Trial initiation date • Combination therapy

KMT2A (Lysine Methyltransferase 2A)

MLL rearrangement

cytarabine • methotrexate • vincristine • revumenib (SNDX-5613) • Oncaspar liquid (pegaspargase) • fludarabine IV • Asparlas (calaspargase pegol-mknl) • Starasid (cytarabine ocfosfate)

9ms

The MLL-Menin Interaction is a Therapeutic Vulnerability in NUP98-rearranged AML. (PubMed, Hemasphere)

Revumenib treatment blocks leukemic engraftment and prevents leukemia-associated death of immunodeficient mice transplanted with NUP98::NSD1 FLT3-ITD-positive patient-derived AML cells. These results demonstrate that NUP98-rearranged AMLs are highly susceptible to inhibition of the MLL-Menin interaction and suggest the inclusion of AML patients harboring NUP98 fusions into the clinical evaluation of Menin inhibitors.

9 months ago

Journal

FLT3 (Fms-related tyrosine kinase 3) • NUP98 (Nucleoporin 98 And 96 Precursor 2) • CDK6 (Cyclin-dependent kinase 6) • NSD1 (Nuclear Receptor Binding SET Domain Protein 1) • MEIS1 (Meis Homeobox 1)

FLT3-ITD mutation • FLT3 mutation • FLT3 wild-type

revumenib (SNDX-5613)

10ms

Expanded Access Program for SNDX-5613 (clinicaltrials.gov)

P=N/A, Available, Syndax Pharmaceuticals

10 months ago

New trial

NPM1 (Nucleophosmin 1) • NUP98 (Nucleoporin 98 And 96 Precursor 2)

NPM1 mutation

revumenib (SNDX-5613)

11ms

Breakthrough treatment choice for Acute Myeloid Leukemia in pediatric and adult patients: Revumenib, an oral selective inhibitor of KMTA2Ar. (PubMed, Rare Tumors)

No abstract available

11 months ago

Journal

revumenib (SNDX-5613)

11ms

P1b, N=28, Not yet recruiting, National Cancer Institute (NCI)

11 months ago

New P1 trial • Combination therapy

FLT3 (Fms-related tyrosine kinase 3) • NPM1 (Nucleophosmin 1) • KMT2A (Lysine Methyltransferase 2A)

FLT3-ITD mutation • FLT3 mutation • NPM1 mutation • MLL rearrangement • FLT3 wild-type • MLL mutation

daunorubicin • revumenib (SNDX-5613) • Starasid (cytarabine ocfosfate)

12ms

A Phase 1B Study Assessing the Safety and Activity of SNDX-5613(revumenib) in Combination with Age-Modified Chemotherapy in NewlyDiagnosed patients with KMT2Ar acute lymphoblastic leukemia (ALL) oracute leukemia with ambiguous lineage (ALAL). (SWOG-Spring 2023)

No abstract available

12 months ago

Clinical • P1 data • Combination therapy

KMT2A (Lysine Methyltransferase 2A)

revumenib (SNDX-5613)

12ms

REVUMENIB IN PATIENTS WITH ACUTE LEUKEMIAS: COMPASSIONATE USE PROGRAM EXPERIENCE (EHA 2023)

From Oct 2019 to Dec 2022, 36 pts (20 female) with R/R acute leukemia received REV. Ages ranged from 1.2 to 71 years (20 pediatric pts [<18 y]). Leukemia subtypes were acute myeloid leukemia (AML; n=30), acute lymphoblastic leukemia (n=4), and mixed phenotype acute leukemia (n=2).

12 months ago

Clinical

NPM1 (Nucleophosmin 1) • KMT2A (Lysine Methyltransferase 2A) • CD34 (CD34 molecule)

NPM1 mutation • KMT2A rearrangement • MLL rearrangement

revumenib (SNDX-5613)