Revuforj (revumenib)

P1, N=76, Active, not recruiting, Syndax Pharmaceuticals | Recruiting --> Active, not recruiting

Revumenib is a small-molecule inhibitor that selectively disrupts the menin-MLL interaction, and it is now in clinical use for treatment of MLLr and NPM1-mutated (NPM1c) acute leukemia...Immunocompromised mice engrafted with JUND-deficient leukemia cells exhibited reduced tumor burden compared to control mice engrafted with wild type leukemic cells. These findings reveal a role for JUND in MLLr AML and suggest that targeting JUND transcription factor activity enhances the efficacy of menin-MLL inhibitors towards MLLr leukemic cells.

Notably, the systemic delivery of chemically optimized siNPM1c via lipid nanoparticles (LNPs) significantly reduced leukemogenesis, and enhanced the therapeutic efficacy of the menin inhibitor revumenib and overcame its resistance in vivo...Targeting NPM1c with siRNA disrupts this interaction, reverses the oncogenic epigenetic landscape, and suppresses transcription. Our findings demonstrate that silencing NPM1c effectively suppresses AML by dismantling a pathogenic KAT7/p300-dependent acetylome, highlighting the potential of LNP‑delivered siNPM1c as a promising therapeutic strategy, either as a monotherapy or in combination with menin inhibition.

This case highlights the diagnostic complexity and therapeutic implications of isolated extramedullary AML relapse and underscores the need to perform genetic testing at the site of disease recurrence-especially without bone marrow involvement of relapsed disease. The authors have confirmed clinical trial registration is not needed for this submission.

P1, N=20, Not yet recruiting, M.D. Anderson Cancer Center | Initiation date: May 2026 --> Nov 2026

Novel menin inhibitors, including revumenib, bleximenib, ziftomenib, and enzomenib, are currently under clinical evaluation, and selected updated clinical results were presented at the 2025 American Society of Hematology (ASH) Annual Meeting. This brief review summarizes the key findings and discusses the emerging clinical questions regarding combination strategies, treatment sequencing, and molecularly defined use of menin inhibitors.

Despite a subsequent episode of torsades de pointes, the patient continued revumenib for an additional 29 days without further arrhythmias until discontinuation because of worsening acute myeloid leukemia shown by bone marrow biopsy. Although current guidance recommends discontinuation of revumenib in the setting of life-threatening arrhythmias, this case highlights the importance of individualized risk-benefit assessment and supportive strategies when treatment is pursued as a last resort.

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.

P1, N=38, Recruiting, National Cancer Institute (NCI) | N=28 --> 38

P2, N=90, Not yet recruiting, SWOG Cancer Research Network

P1, N=0, Withdrawn, M.D. Anderson Cancer Center | N=32 --> 0 | Trial completion date: Dec 2034 --> May 2026 | Initiation date: Dec 2027 --> May 2026 | Not yet recruiting --> Withdrawn | Trial primary completion date: Dec 2032 --> May 2026

Currently, several small-molecule menin inhibitors are being tested in combination with conventional therapies. This publication reviews the recent progress in investigating the clinical evidence of menin inhibitors (revumenib, ziftomenib, bleximenib, enzomenib, BMF-219, emilumenib) toward aggressive leukemias, guides future study and optimal treatment for patients with this type of leukemia.