NPM1 mutation

P3, N=875, Recruiting, Stichting Hemato-Oncologie voor Volwassenen Nederland | Not yet recruiting --> Recruiting | N=328 --> 875

The menin-lysine methyltransferase 2A acute leukemia (KMT2A) protein-protein interaction has emerged as a clinically validated epigenetic target in acute leukemia, following the approval of the reversible menin inhibitor Revumenib for KMT2A-rearranged and nucleophosmin 1 (NPM1)-mutant disease...Across all chemical classes, sustained target engagement-rather than equilibrium affinity alone-emerges as the dominant determinant of antileukemic efficacy. By integrating structure-activity relationship (SAR), resistance mechanisms, safety considerations, and translational scope across oncology and metabolic indications, this review provides a roadmap for the rational design of next-generation menin inhibitors and establishes menin as a model system for modern epigenetic drug discovery.

Not available.

We critically evaluate the preclinical and clinical development of menin inhibitors, including revumenib, ziftomenib, bleximinib, and icovamenib, summarizing efficacy signals in relapsed/refractory disease, safety profiles, and emerging resistance mechanisms. Special attention is given to combination strategies with venetoclax, FLT3 inhibitors, chemotherapy, and epigenetic agents, which aim to enhance response durability and mitigate resistance. Finally, we discuss ongoing clinical trials, unresolved challenges in patient selection and sequencing, and future directions for integrating menin inhibition into precision-based treatment paradigms for acute leukemia.

P2, N=29, Active, not recruiting, Grupo Cooperativo de Estudio y Tratamiento de las Leucemias Agudas y Mielodisplasias | Recruiting --> Active, not recruiting

P2, N=35, Not yet recruiting, Second Affiliated Hospital, School of Medicine, Zhejiang University

P=N/A, N=100, Recruiting, Peking University People's Hospital

Not available.

Regarding mutation detection in low amounts of extracted DNA, the relationship between Tm and the blast percentage is an advantageous characteristic of the HRM method. As shown in a previous study, the use of NPM1 and IDHs for the detection of Minimal Residual Disease (MRD) by HRM is a sensitive method.

Furthermore, PAMT-001 demonstrated potential for use in precision medicine, particularly for patients with chemotherapy-resistant and NPM1-mutated acute myeloid leukemia. PAMT-001 is a potent ERRα-targeting anticancer agent capable of inducing anticancer effects through pyroptosis, autophagic cell death, and apoptosis-a newly termed mechanism referred to as "PAAoptosis." It holds significant potential for the treatment of both hematological and solid cancers.

P1, N=22, Recruiting, Richard Stone, MD | Trial completion date: Mar 2027 --> Mar 2028 | Trial primary completion date: Mar 2026 --> Mar 2027