Revuforj (revumenib) / Syndax Pharma - LARVOL DELTA

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 | Sponsor: M.D. Anderson Cancer Center

New P1 trial • Hematological Malignancies • Leukemia • Oncology • Pediatrics

Advances in menin inhibition in acute myeloid leukemia. (PubMed, Trends Cancer) - "Successes in clinical investigation have led to recent FDA approval of revumenib for KMT2Ar AML, with numerous trials examining menin inhibitors as monotherapy and in combination with other antileukemic drugs ongoing. Although menin inhibitors represent a major advancement in AML treatment, acquired resistance is an evolving barrier to efficacy. Here, we examine the biological rationale for menin inhibition and discuss the landscape of clinical trials and resistance mechanisms associated with menin inhibitors."

Journal • Review • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • KMT2A • NPM1 • NUP98

Moving the Needle in KMT2A Rearranged Pediatric B-Cell Acute Lymphoblastic Leukemia: Newer agents and novel approaches. (PubMed, Clin Hematol Int) - "Recent clinical trials have shown a significant improvement in response rates and survival outcomes in infantile and pediatric non-infant patients with KMT2A-r B-ALL when treated with blinatumomab-containing regimens...In the salvage settings the use of tisagenlecleucel chimeric antigen receptor (CAR) T-cell therapy has led to high response rates and durable remissions in pediatric KMT2A-r B-ALL. Recently, inotuzumab ozogamicin was approved in pediatric (>1 year) relapsed/refractory B-ALL, widening immunotherapy-based salvage options...Additionally, the approval of menin inhibitors like revumenib in KMT2A-r pediatric acute leukemias provides another treatment option in the salvage setting for this high-risk pediatric B-ALL subtype. These targeted agents are positively altering the treatment approaches and outcomes in pediatric KMT2A-r B-ALL, and the use of better residual disease monitoring with next generation sequencing might further help to refine treatment..."

IO biomarker • Journal • Review • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • Hematological Malignancies • Leukemia • Oncology • Pediatrics • CD22 • KMT2A

OUTCOMES OF RELAPSED OR REFRACTORY ACUTE MYELOID LEUKEMIA AFTER MENIN INHIBITION (EHA 2025) - "Prior to MENINi, 84% (n=43) of patients had received intensive chemotherapy (IC) and 73% (n=37) had received venetoclax (VEN)-based therapy...The most used MENINi was revumenib (n=40, 78%), followed by ziftomenib (n=9, 18%)...Of these 4 responders, 3 received AZA (azacitidine)/VEN, 1 received FLAG-IDA/VEN, and all 4 were VEN-naïve...No patients with FLT3-ITD after MENINi responded to further therapy, including 8 treated with gilteritinib (GILT), despite 4 of them being GILT-naïve... MENINi are promising in AML, but outcomes after failure are poor. Responses to post-MENINi therapy can be seen with VEN-based regimens in VEN-naïve patients. Studies focused on sequencing as well as preventing and overcoming MENINi resistance are needed."

Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • FLT3 • KMT2A • MEN1 • NPM1 • NUP98 • WT1

SEQUENTIAL ALLOGENEIC STEM CELL TRANSPLANTATION FOR VENETOCLAX-EXPOSED RELAPSED OR REFRACTORY ACUTE MYELOID LEUKEMIA OR MYELODYSPLASTIC SYNDROME WITH INCREASED BLASTS-2 (EHA 2025) - "Three different 10-day preconditioning backbone regimens were used: ACTIVE (actinomycin D 12.5 mcg/kg (days 1-3), cytarabine 20 mg/m2 (days 1-10), venetoclax 600 mg (days 1-10), De-ACTIVE (decitabine 20 mg/m2 (days 1-10) added to ACTIVE) or De-CAVE (decitabine 20 mg/m2 (days 1-10), cytarabine 20 mg/m2 (days 1-10), venetoclax 600 mg (days 1-10)...Gilteritinib, revumenib, and BCR-ABL1 inhibitor exposure was reported in 16 % (4/25), 12 % (3/25), and 8 % (2/25), respectively...Cladribine (40 %, 10/25), gilteritinib (12 %, 3/25), trametinib (16 %, 4/25), navitoclax (28 %, 7/25), and ponatinib (8 %, 2/25) were added to the preconditioning... Upfront sequential alloSCT demonstrates high antileukemic efficacy in poor-risk, R/R AML, or MDS-IB2 patients with previous venetoclax exposure."

Acute Myelogenous Leukemia • Infectious Disease • Mucositis • Myelodysplastic Syndrome • Septic Shock • Transplantation • BCR • TP53

REM-422, A SMALL MOLECULE MYB MRNA DEGRADER, DEMONSTRATES ANTI-LEUKEMIC ACTIVITY AS A MONOTHERAPY AND IN COMBINATION WITH STANDARDS OF CARE IN PRECLINICAL MODELS OF AML (EHA 2025) - P1 | "REM-422's anti-proliferative activity was unchanged in the resistant models, which is consistent with the differentiated mechanism of action of REM-422 compared to these standards of care.The activity of REM-422 was assessed in vitro in combination with AML standards of care by co-treating leukemia cell lines with REM-422 and other agents including venetoclax, gilteritinib, revumenib, and azacitidine. These data support the therapeutic potential for REM-422 in AML patients both as monotherapy and in combination therapy."

Combination therapy • Monotherapy • Preclinical • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • ANXA5 • CD14 • FLT3 • ITGAM • KMT2A • MYB

Syndax Announces FDA Priority Review of sNDA for Revuforj (revumenib) in Relapsed or Refractory mNPM1 Acute Myeloid Leukemia (GlobeNewswire) - "Syndax Pharmaceuticals...announced that the U.S. Food and Drug Administration (FDA) has granted Priority Review for its supplemental New Drug Application (sNDA) for Revuforj (revumenib) for the treatment of relapsed or refractory (R/R) mutant NPM1 (mNPM1) acute myeloid leukemia (AML). The sNDA is being reviewed under the FDA's Real-Time Oncology Review (RTOR) program and has been assigned a Prescription Drug User Fee Act (PDUFA) target action date of October 25, 2025....The sNDA is supported by positive pivotal data from the AUGMENT-101 trial of revumenib in patients with R/R mNPM1 AML."

FDA filing • PDUFA • Priority review • Acute Myelogenous Leukemia

PATIENTS WITH RELAPSED OR REFRACTORY (R/R) NUCLEOPHOSMIN 1–MUTATED (NPM1M) ACUTE MYELOID LEUKEMIA (AML): UPDATED RESULTS FROM THE PHASE 2 AUGMENT-101 STUDY (EHA 2025) - P1/2 | "The prognosis for R/R NPM1m AML is poor, with only 16% of pts expected to survive 1 y; outcomes after salvage therapy with venetoclax are low, with overall response rates (ORRs) ranging from 6% to 23%, demonstrating a high unmet medical need. Revumenib continues to demonstrate clinically meaningful responses in this heavily pretreated, older population with R/R NPM1m AML. The safety profile remains consistent with previous reports. These findings support further investigation of revumenib as a treatment in earlier lines of therapy and in combination."

Clinical • P2 data • Acute Myelogenous Leukemia • Anemia • Febrile Neutropenia • Hematological Disorders • Hematological Malignancies • Leukemia • Neutropenia • Oncology • Pediatrics • KMT2A • NPM1

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

REVUMENIB ACTIVITY IN PATIENTS WITH ACUTE LEUKEMIA WITH NUP98R: RESULTS FROM THE AUGMENT-101 PHASE 1 STUDY (EHA 2025) - P1/2, P2 | "The safety profile of revumenib in pts with AL with NUP98r was consistent with previous reports, with no new safety signals observed (Issa et al, Nature. 2023; Issa et al, J Clin Oncol. 2025)."

Clinical • P1 data • Anemia • Bone Marrow Transplantation • Hematological Disorders • Hematological Malignancies • Leukemia • Oncology • Pediatrics • KMT2A • NPM1 • NUP98

DIRECT FUNCTIONAL HOXA9/DNA BINDING COMPETITORS VERSUS EPIGENETIC INHIBITORS OF HOXA9 EXPRESSION ON CELL PROLIFERATION, DEATH AND DIFFERENTIATION PROCESSES IN THE MODEL OF MLL-REARRANGED ACUTE MYELOID LEUKAEMIA (EHA 2025) - "For this purpose, we first focused on genes and pathways that were deregulated, utilizing transcriptomic data to identify both shared and distinct deregulated pathways across the approaches and then evaluated cellular effects based on global cell survival and further identified the impact of cell death, cell cycle and cell differentiation using direct HOXA9/DNA binding competitors (HOXA9i) or epigenetic MLL inhibitors of HOXA9 (Revumenib, MI-503, MM-102, Pinometostat/EPZ5676 and EPZ004777).The present work highlights common and different features from transcriptomic analysis following direct or indirect HOXA9 inhibition. In summary, the use of direct HOXA9 functional inhibitors that target the DNA binding domain, such as DB1055 and DB818, seems to be more effective in promoting differentiation of MLL-r cells compared to the epigenetic MLL inhibitors that operate at the level of HOXA9 expression. This observation offers compelling justification for advancing clinical..."

Epigenetic controller • IO biomarker • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • CD14 • CD40 • CD86 • CDKN1A • DOT1L • HOXA9 • IL1B • ITGAM • KMT2A • WDR5

A PHASE 1 STUDY OF REVUMENIB + INTENSIVE CHEMOTHERAPY IN PATIENTS WITH NEWLY DIAGNOSED ACUTE MYELOID LEUKEMIA HARBORING GENETIC ALTERATIONS IN KMT2A, NPM1, OR NUP98 (SNDX-5613-0708) (EHA 2025) - P1 | "Patients will receive induction therapy of revumenib in combination with cytarabine 200 mg/m2 and either daunorubicin 60 mg/m2 or idarubicin 12 mg/m2. Exploratory endpoints include the percentage of patients who achieve complete remission (CR), rate of composite CR, objective response rate, time to response, duration of response, relapse-free survival, event-free survival, and OS. As of March 1, 2025, this study is actively recruiting patients in the United States, Australia, and the United Kingdom, with additional sites opening in Canada, the Netherlands, and Spain."

Clinical • P1 data • Acute Myelogenous Leukemia • Bone Marrow Transplantation • Hematological Malignancies • Leukemia • Oncology • KMT2A • NPM1 • NUP98

VENETOCLAX AND AZACYTIDINE IN CHILDHOOD MYELODYSPLASTIC SYNDROMES AND ACUTE MYELOID LEUKEMIA: THE AIEOP EXPERIENCE (EHA 2025) - "Among 11 patients with KMT2A-rearranged AML, 7 achieved CR, 2 PR, while 2 presented a blast increase and were rescued with revumenib, achieving CR. We report a nationwide experience with ven/aza in pediatric high-risk myeloid diseases, showing a relatively favorable outcome in patients bridged to HCT, with manageable toxicity. Our findings support future prospective protocols using ven/aza for MDS-EB and t-MDS/AML. Further biological characterization of specific genetic subgroups, such as KMT2A-rearranged malignancies, may help refine the role of Bcl-2 inhibition and the prediction of treatment response."

Clinical • Acute Myelogenous Leukemia • Febrile Neutropenia • Hematological Disorders • Hematological Malignancies • Infectious Disease • Leukemia • Myelodysplastic Syndrome • Neutropenia • Oncology • Pediatrics • FLT3 • KMT2A

UNCOVERING CD180 AS A NOVEL MARKER AND THERAPEUTIC TARGET OF CHEMORESISTANCE AND RELAPSE IN KMT2A-REARRANGED PAEDIATRIC AML. (EHA 2025) - "CD180+ cells were enriched in quiescent clusters (p<2.2e-16) persisting through relapse (33.2% of total cells) that had co-expression of CD33 and CD93 and were enriched in oxidative phosphorylation, inflammatory response, and TNF-α signaling pathways (NES=1.52, 1.67, 1.62; p-adj=0.006, 1.54e-04, 3.17e-04) known to contribute to chemoresistance.In vitro studies showed that CD180 was upregulated in cytarabine and mitoxantrone chemoresistant versus parental THP-1 (p<0.05)...Revumenib (SNDX-5613) menin-inhibitor significantly decreased CD180-expressing cells% (p=0.0006)... KMT2A-r PAML showed low expression of conventional MRD markers, including CD34. CD180 was highly expressed in KMT2A-r PAML but minimally in normal HSCs. CD180 identifies a chemoresistant, quiescent LSC population expanding at relapse, supporting its use in MRD tracking."

Acute Myelogenous Leukemia • Inflammation • Pediatrics • CD123 • CD33 • CD34 • CD93 • IL3RA • KIT • KMT2A • MLLT3 • TNFA

TARGETING ZEB1 TO ENHANCE MENIN-INHIBITOR SENSITIVITY IN KMT2A-MLLT3 ACUTE MYELOID LEUKEMIA THROUGH MODULATION OF MICRORNA-204 (EHA 2025) - "Finally, we investigated 5-azacytidine (5-Aza) treatment as a strategy to restore miR-204 expression in AML.We identified Zeb1 expression exclusively in a subset of primitive leukemic cells anti-correlated with Hoxa9/Meis1, suggesting an alternative survival pathway in these cells...We then showed an increased sensitivity of these cells to MENIN inhibition (revumenib) mediated by miR-204, while 204-KO cells responded by activating Zeb1, demonstrating its potential as a resistance mechanism... This study establishes miR-204 as a key regulator of ZEB1 in KMT2A-MLLT3 AML, suppressing leukemic stemness and therapy resistance. We show miR-204 enhances MENIN inhibitor sensitivity, while its depletion may drive resistance via ZEB1 activation. Notably, 5-Aza reactivates miR-204 expression, offering a strategy to improve MENIN inhibitor responsiveness in KMT2A-MLLT3 AML."

Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • CD34 • HOXA9 • KMT2A • MEIS1 • MIR204 • MLLT3 • ZEB1

PLINABULIN AND SELUMETINIB INDUCE AAMS REPROGRAMMING INTO M1-LIKE MACROPHAGES AND REDUCE AML CELL VIABILITY (EHA 2025) - "We then evaluated gene expression changes under the combination treatment of AZD6244 and revumenib (a Menin inhibitor) to assess AAM repolarization. In conclusion, we found that BPI-2358 and AZD6244 can reprogram AAMs into M1-like macrophages, enhancing their pro-inflammatory features and phagocytic capacity while reducing AAM-CD163⁺ levels and AML viability, representing a promising therapeutic approach in combination with targeted therapies in AML."

Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • CD163 • CD34 • CD80 • KIT • MN1 • MRC1 • NOS2 • TNFA

AZACITIDINE, VENETOCLAX, AND REVUMENIB FOR NEWLY DIAGNOSED OLDER ADULTS WITH ACUTE MYELOID LEUKEMIA (AML) AND NPM1 MUTATION OR KMT2A REARRANGEMENT: UPDATED RESULTS FROM THE BEAT AML CONSORTIUM (EHA 2025) - P1/2, P3 | "AVR has demonstrable clinical activity with manageable safety in ND older adults with NPM1m or KMT2Ar AML with ORR of 88% in all pts and 100% in response-evaluable pts within 2 cycles of treatment. A randomized phase 3 study (NCT06652438) of AVR vs. AV-placebo in ND older adults with NPM1m is in development based on these findings."

Clinical • Acute Myelogenous Leukemia • Hematological Malignancies • Infectious Disease • Leukemia • Oncology • Respiratory Diseases • Septic Shock • KMT2A • NPM1

Menin inhibitors from monotherapies to combination therapies: clinical trial updates from 2024 ASH annual meeting. (PubMed, J Hematol Oncol) - "Following the promising outcomes of the two pioneering menin inhibitors, revumenib and ziftomenib, other menin inhibitors, including bleximenib, enzomenib, BN-104 and HMPL-506 are currently under investigation in clinical trials. Several trials presented their initial outcomes at the 2024 ASH Annual Meeting. This review highlights the key outcomes of these pivotal clinical trials."

Journal • Review • Hematological Malignancies • Leukemia • Oncology • KMT2A • MEIS1 • NPM1 • NUP98

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

Syndax Announces Publication of Revumenib Data from the BEAT AML Trial in the Journal of Clinical Oncology and Simultaneous Presentation at EHA 2025 (GlobeNewswire) - P1b/2 | N=2,000 | NCT03013998 | "As of September 2024, 43 patients were enrolled and treated in BEAT AML across two dose levels of revumenib (113 mg q12 or 163 mg q12h with strong CYP3A4 inhibitor azoles) in combination with venetoclax and azacitidine....In the intent-to-treat population, the observed rate of complete remission (CR) was 67% (29/43), composite complete remission (CRc) was 81% (35/43), and the overall response rate (ORR) was 88% (38/43). Among 37 patients with measurable residual disease (MRD) response assessment, 100% were MRD negative by centralized flow cytometry testing (sensitivity of 0.02%). The median duration of CRc was 12.0 months (95% CI: 7.8-not reached). 23% (10/43) of patients had proceeded to hematopoietic stem cell transplantation (HSCT) as of the February 2025 data cut off. In an early analysis of survival from this single-arm trial (median follow-up of 6.9 months), the median overall survival (OS) observed was 15.5 months (95% CI: 9.5-19.5)."

P1 data • Acute Myelogenous Leukemia

Relapsed/Refractory mNPM1 and NUP98r Acute Leukemia from AUGMENT-101 Trial at EHA 2025 (GlobeNewswire) - P1/2 | N=413 | AUGMENT-101 (NCT04065399) | Sponsor: Syndax Pharmaceuticals | "At EHA 2025, the Company will highlight consistent results from all the efficacy-evaluable R/R mNPM1 AML patients (n=77) in the Phase 2 portion of AUGMENT-101 (DCO: September 2024). In this population, the median age was 63 (11-84), 20% had received four or more prior lines of therapy (median prior lines: 2), and 74% had previously received venetoclax...The complete remission plus complete remission with partial hematologic recovery (CR+CRh) rate was 26% (20/77; 95% CI: 17%-37%). The median duration of CR/CRh response was 4.7 months (95% CI: 2.1-8.2) and the median time to first CR/CRh was 2.8 months (range: 0.9-8.8). Minimal residual disease (MRD) status was assessed in 19 of 20 patients who achieved CR/CRh, 63% (12/19) of whom were MRD negative...The overall response rate (ORR)1 was 48% (37/77; 95% CI: 37%-60%)."

P2 data • Acute Myelogenous Leukemia • Transplantation

Detection of KMT2A partial tandem duplication (PTD) in AML by whole genome sequencing (WGS): Addressing limitations of traditional techniques in the era of revumenib approval. (ASCO 2025) - "WGS is an effective tool for detecting KMT2A alterations that may be missed by traditional techniques such as NGS targeted capture, FISH or cytogenetics. 100% concordance was observed between WGS and RNAseq for KMT2A-PTDs, supporting the reliability of WGS. The FDA approval of menin inhibitors for KMT2A-rearranged AML/ALL suggests potential clinical opportunities for broad tests (WGS) to identify other rearrangements, including KMT2A-PTDs, highlighting the need for further research into targeted anti-leukemia therapies."

Whole genome sequencing • Acute Myelogenous Leukemia • IDH1 • KMT2A • RUNX1 • WT1

Budget impact analysis of revumenib for the treatment of relapsed or refractory acute leukemias with a KMT2A translocation in the United States. (PubMed, J Manag Care Spec Pharm) - "Sensitivity and scenario analyses validated the robustness of the model. The BIM demonstrated that including revumenib in a formulary for adult patients with R/R KMT2At ALs was approximately cost neutral, offering patients access to a targeted treatment with potential for improved clinical outcomes."

HEOR • Journal • Acute Lymphocytic Leukemia • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • KMT2A

Menin Inhibitors in KMT2A-Rearranged and NPM1-Mutated Acute Leukemia: A Scoping Review of Safety and Efficacy. (PubMed, Crit Rev Oncol Hematol) - "Menin inhibitors demonstrate promising clinical activity in molecularly defined leukemias, with Revumenib establishing proof-of-concept for this therapeutic approach. However, challenges remain, including resistance development, optimal timing of therapy initiation, and determination of effective combination strategies. Larger randomized trials with extended follow-up are needed to establish long-term efficacy and safety profiles. The rapid clinical development of multiple agents in this class suggests an expanding role for Menin inhibitors in leukemia treatment paradigms."

Journal • Review • Hematological Malignancies • Leukemia • Oncology • KMT2A • MEN1 • NPM1

Revumenib for Relapsed or Refractory Acute Leukemia With a KMT2A Translocation. (PubMed, Ann Pharmacother) - P1/2 | "Revumenib is an innovative targeted treatment with promising activity in r/r acute leukemia with KMT2Ar."

Journal • Review • Acute Myelogenous Leukemia • Cardiovascular • Febrile Neutropenia • Hematological Disorders • Hematological Malignancies • Infectious Disease • Leukemia • Neutropenia • Oncology • Pediatrics • Thrombosis • Transplantation • KMT2A