Revuforj (revumenib) / Syndax Pharma - LARVOL DELTA

Menin Inhibition With Revumenib for KMT2A-Rearranged Relapsed or Refractory Acute Leukemia (AUGMENT-101). (PubMed, J Clin Oncol) - P1/2 | "Revumenib led to high remission rates with a predictable safety profile in R/R KMT2Ar acute leukemia. To our knowledge, this trial represents the largest evaluation of a targeted therapy for these patients."

Journal • Acute Myelogenous Leukemia • Febrile Neutropenia • Hematological Disorders • Hematological Malignancies • Leukemia • Neutropenia • Oncology • KMT2A • NPM1

Menin inhibition with revumenib for NPM1-mutated relapsed or refractory acute myeloid leukemia: the AUGMENT-101 study. (PubMed, Blood) - P1/2 | "The protocol-defined efficacy-evaluable population for the primary analysis included 64 adult patients (≥3 prior lines of therapy, 35.9%; prior venetoclax, 75.0%). The safety profile of revumenib was consistent with previously reported results. This trial was registered at www.clinicaltrials.gov as NCT04065399."

Journal • Acute Myelogenous Leukemia • Bone Marrow Transplantation • Hematological Disorders • Hematological Malignancies • Leukemia • Oncology • Transplantation • KMT2A • NPM1

Azacitidine, Venetoclax, and Revumenib for Newly Diagnosed NPM1-Mutated or KMT2A-Rearranged AML. (PubMed, J Clin Oncol) - P1/2 | "In older adults newly diagnosed with NPM1m or KMT2Ar AML, the combination of azacitidine, venetoclax, and revumenib was able to be safely administered with high rates of CR and clinical activity."

Journal • Acute Myelogenous Leukemia • Hematological Disorders • KMT2A • NPM1

The All-Oral Combination of Revumenib, Decitabine and Venetoclax for Relapsed or Refractory Acute Myeloid Leukemia (SAVE). (PubMed, J Clin Oncol) - "This combination was associated with high response rates and durable remissions, with an acceptable safety, in heavily pretreated patients with AML harboring alterations susceptible to menin inhibition."

IO biomarker • Journal • Acute Myelogenous Leukemia • Febrile Neutropenia • Hematological Disorders • Hematological Malignancies • Infectious Disease • Leukemia • Neutropenia • Oncology • Respiratory Diseases • Thrombocytopenia • KMT2A • NPM1 • NUP98

GI Toxicity Profile of Menin Inhibitors in KMT2A-Rearranged and NPM1-Mutated Acute Leukemia: A Systematic Review and Meta-Analysis of 526 Patients (ACG 2026) - "Introduction: Menin inhibitors (revumenib, ziftomenib, bleximenib, enzomenib) block the menin-KMT2A interaction to reverse leukemogenesis in KMT2A-rearranged (KMT2Ar) and NPM1-mutated (NPM1m) acute leukemia. : DS of any grade was pooled across 9 arms (N=526, events=58): incidence 10.3% (95% CI 5.0-16.9%; prediction interval [PI] 0-33.9%; I²=73.1%). DS grade â¥3: 3.3% (95% CI 0.4-8.1%; PI 0-20.8%). QTc prolongation: 1.2% (95% CI 0-4.1%)."

Retrospective data • Review • Hematological Malignancies • Leukemia • KMT2A • NPM1

Revumenib As Pre-Emptive Therapy for Measurable Residual Disease in NPM1 mutated or KMT2A-rearranged Acute Myeloid Leukemia: A Domain of the Multi-Arm ALLG AMLM26 Intercept Platform Trial (ASH 2024) - P, P1/2 | "Median age was 62 years (range 19-85), 7 were in CR1, 3 had prior venetoclax exposure and 6 prior intensive therapy. In preliminary analysis, NPM1m ≥1 log10 MRD reduction was recorded in 62.5% (n=5) of pts, including 37.5% (n=3) achieving MRD negativity. Further updates will be presented at the meeting."

Residual disease • Acute Myelogenous Leukemia • Anemia • Febrile Neutropenia • Neutropenia • Thrombocytopenia • KMT2A • NPM1

CLINICAL ACTIVITY OF REVUMENIB IN PATIENTS WITH RELAPSED/REFRACTORY (R/R) NUP98-REARRANGED ACUTE LEUKEMIAS (EHA 2026) - P, P1/2 | "Pts received a median (range) of 3 prior lines of tx (1–7); 20 (77%) received prior venetoclax; and 13 (50%) had prior hematopoietic stem cell transplant (HSCT). The safety profile was manageable, with no tx ‑ related discontinuations or deaths, and AEs consistent with the known effects of menin inhibition. These findings support the development of larger prospective studies, including frontline and combination chemotherapy regimens, to better define the clinical benefit of revumenib in this high ‑ risk, historically undertreated population."

Clinical • Acute Myelogenous Leukemia • Bone Marrow Transplantation • Hematological Malignancies • Leukemia • KMT2A • NPM1 • NUP98

UPDATED RESULTS AND LONGER FOLLOW-UP FROM THE AUGMENT-101 PHASE 2 STUDY OF REVUMENIB IN PATIENTS WITH RELAPSED OR REFRACTORY (R/R) KMT2AR ACUTE LEUKEMIA (EHA 2025) - P1/2 | "Pts were heavily pretreated: 51 (44%) received ≥3 prior therapies, 73 (63%) received prior venetoclax, and 59 (51%) underwent prior hematopoietic stem cell transplant (HSCT).In the efficacy population (n=97), 22 pts (23%; 95% CI, 15%-32%) achieved CR+CRh with a median DOR of 6.4 mo (95% CI, 1.9 mo-NR). Revumenib provides clinically meaningful responses in heavily pretreated pts with R/R KMT2Ar AL across various subgroups and has a manageable safety profile."

Clinical • P2 data • Anemia • Bone Marrow Transplantation • Febrile Neutropenia • Hematological Disorders • Hematological Malignancies • Infectious Disease • Leukemia • Neutropenia • Oncology • Septic Shock • KMT2A

Outcomes after Transplant in Relapsed/Refractory KMT2Ar (MLLr) and mNPM1 (NPM1c) leukemia Patients Achieving Remissions after Menin Inhibition: SNDX-5613 (revumenib) Ph1 Experience (ASH 2022) - P1/2 | "1 was among the 12 patients described in Table 1: a 40 yo F with KMT2Ar AML with FLT3 TKD, and 3 prior lines of therapy including 7+3+midostaurin and HSCT...She then had a molecular relapse and received CPX-351, gemtuzumab, venetoclax, and azacytidine, a 3rd allo-HSCT, and due to persistent positive MRD by flow, she received a donor lymphocyte infusion... In SNDX-5613 patients proceeding to transplant, durable remissions occurred across a range of heavily pre-treated patients. In addition to patients achieving CR/CRh, two patients with CRp also had ongoing remissions post-transplant. AUGMENT-101 continues to enroll patients, agnostic of transplant eligibility, with the option for SNDX-5613 post-transplant maintenance."

Clinical • Acute Myelogenous Leukemia • Bone Marrow Transplantation • Hematological Malignancies • Infectious Disease • Leukemia • Oncology • Septic Shock • Transplantation • FLT3 • KMT2A • NPM1

Phase II Study of the all-oral combination of revumenib (SNDX-5613) with decitabine/cedazuridine (ASTX727) and venetoclax (SAVE) in newly diagnosed AML (ASH 2025) - P1/2 | "ConclusionSAVE, an all-oral combination, shows promising activity in older adults with ND NPM1m or KMT2Ar AMLwho are ineligible for intensive chemotherapy. Ongoing enrollment and longer follow-up are required toestablish the durability of response."

P2 data • Acute Myelogenous Leukemia • Bone Marrow Transplantation • Hematological Disorders • Hematological Malignancies • Idiopathic Pulmonary Fibrosis • Immunology • Infectious Disease • Leukemia • Myelodysplastic Syndrome • Myelofibrosis • Pulmonary Disease • Respiratory Diseases • FLT3 • KMT2A • KRAS • MEN1 • NPM1 • NRAS • NUP98

Updated Results and Longer Follow-up from the AUGMENT-101 Phase 2 Study of Revumenib in All Patients with Relapsed or Refractory (R/R) KMT2Ar Acute Leukemia (ASH 2024) - P1/2 | "Pts were heavily pretreated (median of 2 prior therapies [range, 1-11]), with 51 (44%) receiving ≥3 prior lines, 73 (63%) receiving prior venetoclax, and 59 (51%) underwent prior hematopoietic stem cell transplant (HSCT). The safety profile of revumenib with this longer follow-up is consistent with prior reports. This trial represents the largest evaluation of a targeted therapy for pts with R/R KMT2Ar acute leukemias to date."

Clinical • P2 data • Anemia • Bone Marrow Transplantation • Febrile Neutropenia • Hematological Disorders • Hematological Malignancies • Infectious Disease • Leukemia • Neutropenia • Oncology • Septic Shock • KMT2A

PHASE 1/2 STUDY OF THE ALL-ORAL COMBINATION OF REVUMENIB (SNDX-5613) WITH DECITABINE/CEDAZURIDINE (ASTX727) AND VENETOCLAX (SAVE) IN RELAPSED/REFRACTORY AML (EHA 2026) - P1/2 | "ASTX727 (35/100 mg) was given PO on days 1–5, venetoclax 400 mg PO on days 1–14, and revumenib 113 mg (DL0) or 163 mg (DL1) PO Q12h on days 1–28 with posaconazole or voriconazole prophylaxis. Summary/Conclusion The all-oral combination of revumenib , venetoclax, and decitabine y ields high remission rates in R/R AML with KMT2Ar , NPM1mt , or NUP98r , with durable responses in patients achieving deep remission. Fig.1: Duration of response by genotype"

IO biomarker • P1/2 data • Acute Myelogenous Leukemia • Bone Marrow Transplantation • Febrile Neutropenia • Hematological Disorders • Hematological Malignancies • Infectious Disease • Leukemia • Neutropenia • Respiratory Diseases • Thrombocytopenia • BCL2 • KMT2A • NUP98

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."

Clinical • IO biomarker • Acute Myelogenous Leukemia • BCL2 • BRD4 • CASP3 • CD123 • CD33 • CD99 • CDK4 • CDKN1A • CEBPA • CLEC12A • FLT3 • HEXIM1 • IL3RA • ITGAM • MCL1 • MEF2C • MYC • NPM1 • PBX3 • PLK1 • SMARCA2 • SMARCA4

Resistance mechanisms and therapeutic strategies after menin inhibitor failure in acute myeloid leukemia. (PubMed, Expert Rev Hematol) - "Menin inhibitors, including the FDA-approved agents revumenib and ziftomenib, have emerged as transformative targeted therapies in acute myeloid leukemia (AML), particularly in KMT2A-rearranged (KMT2Ar) and NPM1-mutated (NPM1m) disease. No clinical tests are currently available to reliably predict emerging resistance or early therapeutic failure, and treatment options after menin inhibitor failure remain limited and largely empiric, including, if not previously used, venetoclax-based regimens, mutation-directed therapies, and intensive chemotherapy as a bridge to allogeneic HSCT. Emerging preclinical data identify key vulnerabilities, including bypass signaling, apoptotic dependence, and epigenetic escape, providing a rationale for next-generation combination strategies, ideally in the frontline setting to maximize the chance of success and minimize the risk of clonal escape."

Journal • Review • Acute Myelogenous Leukemia • Bone Marrow Transplantation • Hematological Malignancies • Leukemia • Oncology • Transplantation • KMT2A • NPM1

Preliminary data from the ongoing Phase 1 study of the menin-MLL inhibitor enzomenib (DSP-5336) in combination with venetoclax and azacitidine in patients with relapsed or refractory Acute Myeloid Leukemia (ASH 2025) - P1/2 | "Median age was 50 yrs (21-76), 56% were female andmedian prior regimens was 2 (1-4); 3 pts (16.7 %) had prior allogeneic stem cell transplant (SCT), 6 pts(33.3%) had prior VEN, and 5 pts (27.8%) received prior menin inhibitor (2 ziftomenib, 1 revumenib, 2enzomenib). Preliminary data show ENZO up to 300 mg BID to be well tolerated in combination withVEN/AZA with no DLTs in 18 pts with R/R KMT2Ar or NPM1m AML. No QT prolongation was reported andthere was 1 report of non-serious DS. Promising preliminary clinical activity has been observed,particularly in pts without prior VEN or menin exposure (100% ORR and 67% CRc rate)."

Clinical • Combination therapy • P1 data • Acute Myelogenous Leukemia • Central Nervous System Leukemia • Hematological Disorders • Hematological Malignancies • Infectious Disease • Leukemia • Leukopenia • Neutropenia • Septic Shock • Thrombocytopenia • FLT3 • KMT2A • NPM1

Identifying novel ’druggable’ targets via Npm1A-turboid fusion and mass spectrometry to overcome genetic or adaptive resistance to menin inhibitors in mtNPM1 AML (ASH 2025) - "Treatment with revumenib may also cause emergenceof hot spot mutations in menin (e.g., S160T, M327V, M327I, G331D, G331R, and T349M) exhibitingreduced affinity to MI-binding...OCI-AML3 MEN1-M327I cells were resistant toSNDX-50469, ziftomenib, and DS1594b, but sensitive to the second-generation MI, bleximenib, aspreviously reported.To identify novel 'druggable' targets in mtNpm1 AML cells either sensitive or resistant to MI, we knockedin TurboID by CRISPR/Cas9 into the C-terminus of the mtNpm1 gene in OCI-AML3 cells...When combined with a BET inhibitor (pelabresib) ora novel dual BET/HAT inhibitor (NEO2734/EP31670), both RocA and talazoparib induced synergisticlethality in the sensitive OCI-AML3 and OCI-AML2-Npm1A KI, as well as the MI-resistant (OCI-AML3-Menin-M327I or the OCI-AML3 MITR) cells...Exvivo treatment with EP31670 and RocA or talazoparib induced synergistic loss of viability in MI (SNDX-50469)-resistant, patient-derived (N = 3) mtNpm1 AML cells. In the..."

IO biomarker • Acute Myelogenous Leukemia • AURKA • CDK9 • CDKN1A • EIF4A1 • EIF4A2 • FLT3 • HOXA9 • IL7R • IRAK4 • KMT2A • MEIS1 • MEN1 • MYC • NPM1 • PLK1 • S100A8 • SF3B1 • SMARCA2 • TP53

Revumenib as maintenance for AML following allogeneic stem cell transplantation. (ASCO 2026) - P, P1/2 | "Pre-SCT, revumenib was given as monotherapy per AUGMENT-101 (NCT04065399, n = 8) or Expanded Access (NCT05918913, n = 2) or with oral decitabine and venetoclax per SAVE (NCT05360160, n = 11). Revumenib maintenance post-SCT was feasible in this heavily pretreated cohort. Thrombocytopenia was common often requiring dose modification, but no other significant toxicities were observed. Outcomes appear favorable compared to historical cohorts, supporting prospective evaluation of menin inhibition as maintenance."

Clinical • Acute Myelogenous Leukemia • Graft versus Host Disease • Hematological Disorders • Immunology • Infectious Disease • Septic Shock • Thrombocytopenia • Transplantation • KMT2A • NUP98

Real-World Experience With Revumenib: A Single-Center Analysis of Efficacy and Tolerability (SOHO 2026) - "Median number of prior lines of therapy was 2; 72% received prior venetoclax and 31% underwent prior HSCT.Of the group, 7 patients received revumenib monotherapy; 22 received revumenib combination therapy. These findings support revumenib as a safe and effective therapeutic option in heavily pretreated AML, with broad activity in combination and in the MRD+ setting. AML: acute myeloid leukemia, CR: complete remission, ELN: European LeukemiaNet, HSCT: hematopoietic stem cell transplantation; KMT2Ar: lysine methyltransferase 2A–rearranged, MRD: measurable residual disease, NPM1: nucleophosmin 1, NUP98r: nucleoporin 98 and 96 precursor–rearranged, ORR: overall response rate, QTcF: corrected QT interval using Fridericia's formula. Research funding provided by Syndax."

Clinical • Real-world • Real-world evidence • Acute Myelogenous Leukemia • Oncology • KMT2A • NPM1 • NUP98

Successful treatment of relapsed KMT2A rearranged AML with central nervous system involvement using revumenib in combination with venetoclax and azacitidine: A case report. (PubMed, Ther Adv Hematol) - "This case indicates that the salvage strategy incorporating Revumenib, venetoclax, azacitidine, and DLI not only exhibits potential for achieving deep remission in KMT2A-rearranged AML but also aids in controlling central nervous system infiltration, thereby providing a novel therapeutic direction for patients with relapsed AML. Further studies involving larger sample sizes are required to assess the long-term survival benefits of this strategy."

Journal • Acute Myelogenous Leukemia • Bone Marrow Transplantation • Hematological Malignancies • Infectious Disease • Leukemia • Oncology • Transplantation • AFDN • KMT2A

Characterization of Immunophenotypic Changes Following Menin Inhibition in Acute Myeloid Leukemia (SOHO 2025) - "Design: We identified 55 patients with relapsed/refractory AML treated with revumenib monotherapy at our center under a phase 1/2 clinical trial or via compassionate use... The median age was 25 years (range, 0.8-79 years), with 42 (76%) patients previously treated with venetoclax and 31 (56%) patients relapsed post-transplant... AML following menin-i treatment frequently exhibits phenotypic shifts, either in differentiation state or antigen expression patterns/intensity."

Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • CD133 • CD14 • CD34 • CD36 • ICAM1 • ITGB3 • KIT • KMT2A • MPO • NPM1 • PTPRC • SCARB1

CHARACTERIZATION OF IMMUNOPHENOTYPIC CHANGES FOLLOWING MENIN INHIBITION IN ACUTE MYELOID LEUKEMIA (EHA 2024) - " We identified 55 pts with R/R AML treated with revumenib monotherapy at our center under the phase 1/2clinical trial or via compassionate use...8-79), with 42 pts (76%) previously treated with venetoclax, and 31 pts(56%) had relapsed post-transplant... Acute myeloid leukemia following treatment with menin inhibitors frequently exhibits phenotypic shifts,manifested either by the state of differentiation (myeloid vs. monocytic) or patterns and/or intensity of antigenexpression. Awareness of these changes is crucial for an accurate assessment of measurable residual disease vsan ongoing response and a differentiation effect which requires further investigation."

Acute Myelogenous Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Oncology • CD133 • CD14 • CD34 • CD36 • ICAM1 • ITGB3 • KIT • KMT2A • MPO • NPM1 • PTPRC • SCARB1

Postmarketing Safety Signals of Revumenib (Menin-KMT2A Inhibitor) vs Acute Myeloid Leukemia-Targeted Therapies: A Class-Restricted Disproportionality Analysis of the FDA Adverse Event Monitoring System (2016–2026) (SOHO 2026) - " AE reports (January 2016–April 2026) were extracted for revumenib (n = 716) and eight targeted AML therapies (n = 70179): ziftomenib, enasidenib, ivosidenib, olutasidenib, gilteritinib, midostaurin, quizartinib, and venetoclax. Analysis of 716 revumenib reports (median age, 50 years; 50.2% male; 57.5% US-sourced; 55.6% serious) identified AML as the recorded indication in 59.2% of cases. Eleven AEs qualified as robust signals. Established toxicities included differentiation syndrome (n = 32; ROR, 9.12; 95% CI, 6.31–13.20), QTc prolongation (n = 29; ROR, 8.88; 95% CI, 6.03–13.08), and decreased platelet count (n = 113; ROR, 3.91; 95% CI, 3.19–4.79)."

Adverse events • Clinical • P4 data • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • FLT3 • KMT2A

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) - P1/2 | "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."

IO biomarker • P1/2 data • Acute Myelogenous Leukemia • Bone Marrow Transplantation • Febrile Neutropenia • Hematological Disorders • Hematological Malignancies • Leukemia • Metabolic Disorders • Musculoskeletal Pain • Nephrology • Neutropenia • Oncology • Pain • Renal Disease • Thrombocytopenia • Transplantation • KMT2A • NPM1 • NUP98

Phase I/II Study of the All-Oral Combination of Revumenib (SNDX-5613) with Decitabine/Cedazuridine (ASTX727) and Venetoclax (SAVE) in R/R AML (ASH 2024) - P1/2 | "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). Conclusions : The all-oral combination SAVE results in high rates of remission in pts with R/R AML with KMT2Ar, NPM1mt or NUP98r. In addition to the R/R cohort, a frontline cohort is now enrolling pts."

IO biomarker • P1/2 data • Acute Myelogenous Leukemia • Bone Marrow Transplantation • Febrile Neutropenia • Hematological Disorders • Hematological Malignancies • Infectious Disease • Leukemia • Metabolic Disorders • Nephrology • Neutropenia • Oncology • Renal Disease • Respiratory Diseases • Thrombocytopenia • KMT2A • NPM1 • NUP98

Menin Inhibitors in NPM1 Mutations and KMT2A Rearrangements in Acute Myeloid Leukemia: Differential Efficacy Across Frontline and Relapsed Settings: A Systematic Review and Meta-Analysis (SOHO 2026) - "Regimens included revumenib- and ziftomenib-based monotherapy and combination approaches...In R/R AML, monotherapy achieved CR/CRh rates of approximately 22% to 23%, whereas frontline triplet therapy (azacitidine, venetoclax, and revumenib) demonstrated CRc rates greater than 80%... Menin inhibitors demonstrate meaningful clinical and molecular activity in molecularly defined AML, with markedly higher efficacy in frontline combination regimens than achieved with R/R monotherapy. These findings highlight their potential as a backbone for precision-based combinations. Prospective randomized studies are needed to define optimal sequencing strategies, combination approaches, and the prognostic relevance of MRD and immunophenotypic evolution."

Retrospective data • Review • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • KMT2A • NPM1