P1, N=16, Not yet recruiting, BioNova Pharmaceuticals (Shanghai) LTD.

Not available.

A 71 years old woman received the MENi revumenib (REV) for relapsed/refractory NPM1m AML...However, to our knowledge, this is the first report ever of MENi induced PG-like ND and cutaneous involvement of DS. This report highlights the fact that ND such as PG, as a manifestation of DS, are a possibly severe adverse effect of MENi.

P1/2, N=413, Recruiting, Syndax Pharmaceuticals | Trial completion date: Dec 2024 --> Dec 2027 | Trial primary completion date: Dec 2024 --> Dec 2027

P1/2, N=414, Active, not recruiting, Biomea Fusion Inc. | Suspended --> Active, not recruiting | Trial primary completion date: Jul 2024 --> Nov 2024

P2, N=190, Active, not recruiting, Biomea Fusion Inc. | Suspended --> Active, not recruiting

Therefore, new drug discovery strategy should be considered in advance. The expert opinion was proposed from several aspects, such as developing diverse chemical structures, discovering covalent inhibitors, designing small molecular PROTACs, and targeting the amino acids mutations for next-generation inhibitors.

P1, N=157, Not yet recruiting, Kura Oncology, Inc.

P1, N=8, Recruiting, Syndax Pharmaceuticals | Trial primary completion date: Sep 2024 --> Dec 2024

P3, N=415, Not yet recruiting, Stichting Hemato-Oncologie voor Volwassenen Nederland

Ziftomenib showed promising clinical activity with manageable toxicity in heavily pretreated patients with relapsed or refractory acute myeloid leukaemia. Phase 2 assessment of ziftomenib combination therapy in the upfront and relapsed or refractory setting is ongoing.

P2, N=8, Recruiting, M.D. Anderson Cancer Center | Not yet recruiting --> Recruiting

P1, N=22, Recruiting, Massachusetts General Hospital | Not yet recruiting --> Recruiting

P1/2, N=43, Recruiting, M.D. Anderson Cancer Center | Trial completion date: Dec 2024 --> Dec 2026 | Trial primary completion date: Dec 2024 --> Dec 2026

Treatment of diabetic wound CD4T cells with a small molecule inhibitor of MLL1 (MI-2) yielded a significant reduction in CD4+TH17 cells and IL17A. This is the first study to identify the MLL1-mediated mechanisms responsible for regulating the TH17/Treg balance in normal and diabetic wounds and define the complex role of Notch signaling in CD4+T cells in wounds, where increased or decreased Notch signaling both result in pathologic wound repair. Therapeutic targeting of MLL1 in diabetic CD4+TH cells may decrease pathologic inflammation through regulation of CD4+T cell differentiation.

"Foundation Medicine, Inc. today announced a collaboration with Syndax Pharmaceuticals...to develop a companion diagnostic for the identification of acute myeloid leukemia (AML) patients harboring an NPM1 mutation. As part of the collaboration, Syndax will also support Foundation Medicine’s efforts to pursue regulatory approval of an assay based on the FoundationOne Heme platform....If approved, the assay could be the first next-generation sequencing companion diagnostic to detect genomic alterations in hematologic neoplasms, including enhancing the identification of patients with NPM1 mutations who may be eligible for revumenib."

P1, N=88, Recruiting, Eilean Therapeutics AU Pty Ltd (A subsidiary of Eilean Therapeutics LLC) | N=40 --> 88

P1; N=27; Not yet recruiting; Sponsor:City of Hope Medical Center

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

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.

It will focus on the pathophysiology of leukemias sensitive to menin inhibition, delineation of how this understanding led to targeted drug development, and data from clinical trials. The important discovery of resistance mechanisms will also be explored, as well as future directions in using menin inhibitors for treating leukemia.

P1, N=40, Recruiting, Eilean Therapeutics AU Pty Ltd (A subsidiary of Eilean Therapeutics LLC) | Not yet recruiting --> Recruiting

P1, N=8, Recruiting, Syndax Pharmaceuticals | Trial completion date: Sep 2024 --> Dec 2024 | Trial primary completion date: May 2024 --> Sep 2024

Additionally, these compounds were predicted as antileukemic, antineoplastic, chemopreventive, and apoptotic agents. The 10 natural compounds can be further explored as potential novel agents for the effective treatment of MLL-mediated leukemia.

P2, N=15, Recruiting, M.D. Anderson Cancer Center | Not yet recruiting --> Recruiting

P1, N=98, Recruiting, Hutchmed | Not yet recruiting --> Recruiting

Finally, we demonstrate significant synergy between revumenib and the DOT1L inhibitor pinometostat in KMT2A-rearranged ALL, suggesting that such drug combinations represent a potent therapeutic strategy for these patients. Collectively, our findings underscore the complexity of resistance mechanisms and advocate for precise patient stratification to optimize the use of menin inhibitors in KMT2A-rearranged acute leukemia.

P2, N=190, Suspended, Biomea Fusion Inc. | Recruiting --> Suspended

P1/2, N=414, Suspended, Biomea Fusion Inc. | Recruiting --> Suspended

Differential gene expression analysis by RNA-seq following combined pharmacological inhibition of SD70 and MI-503 revealed changes in numerous genes, with MYC target genes being the most significantly downregulated. Taken together, these data provide preclinical evidence that the combination of SD70 and MI-503 is a potential dual-targeted therapy for MLL::AF9 AML.

P1, N=22, Not yet recruiting, M.D. Anderson Cancer Center

P1, N=22, Not yet recruiting, Massachusetts General Hospital

P1, N=22, Not yet recruiting, M.D. Anderson Cancer Center

P1, N=98, Not yet recruiting, Hutchmed

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.

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

P1, N=20, Not yet recruiting, LLS PedAL Initiative, LLC

Finally, the combination of VTP50469, an inhibitor of the Menin-MLL interaction, and alpelisib synergistically represses PDX tumors harboring PIK3CA mutations. Together, these findings unveil the metabolic link between PIK3CA mutant tumor cells and the IECs, highlighting AA as the potential target for the treatment of patients with CRC harboring PIK3CA mutations.

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.

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

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

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