P1/2, N=447, Recruiting, Syndax Pharmaceuticals | N=67 --> 447

P3, N=1300, Recruiting, Kura Oncology, Inc. | N=719 --> 1300

P1, N=30, Recruiting, Uma Borate | Trial completion date: Dec 2025 --> Feb 2027 | Trial primary completion date: Dec 2025 --> Jan 2027

P2, N=70, Not yet recruiting, Uma Borate | Initiation date: Jan 2026 --> Apr 2026

Morphologic remission with undetectable measurable residual disease (MRD) by flow cytometry following revumenib was associated with improved overall survival, with a median of 23.6 months compared with 20.8 months in patients with morphologic response and detectable MRD, and 3.2 months in non-responders. In summary, treatment monitoring of AML by flow cytometry, following menin inhibition, requires recognition of phenotypic changes associated with differentiation.

Additionally, treatment with revumenib, a menin inhibitor, increased CLL-1 expression in AML cells harboring mixed-lineage leukemia (MLL) fusion genes or the NPM1 mutation, making them more susceptible to 2-23 CAR T cell-mediated cytotoxicity in vitro. These findings suggest that the clinical efficacy of CAR T cells derived from the novel, high-affinity anti-CLL-1 mAb 2-23 should be tested in patients with CLL-1-positive AML and also that combining 2-23 CAR T cells with revumenib may benefit some patients with CLL-1low/- AML.

P1, N=32, Not yet recruiting, M.D. Anderson Cancer Center | Initiation date: Dec 2025 --> Dec 2027

We tested menin inhibitors (ziftomenib, revumenib, VTP-50469) in 14 primary T-ALL samples and 8 cell lines, representing HOXA-high and HOXA-low genotypes. In conclusion, a subset of T-ALL, defined by high p-MEF2C S222, is sensitive to menin inhibition. Combining ziftomenib with CDK or ERK inhibition offers synergistic efficacy, supporting biomarker-driven clinical trials of this strategy in relapsed/refractory T-ALL.

P1, N=8, Not yet recruiting, Sumitomo Pharma America, Inc.

P1/2, N=66, Active, not recruiting, Institut de Recherches Internationales Servier (I.R.I.S.) | Trial completion date: Jun 2027 --> Dec 2027 | Trial primary completion date: Jun 2026 --> Dec 2026

P2/3, N=411, Not yet recruiting, Kura Oncology Inc.

Compared to each drug alone, co-treatment with SNDX-5613 (revumenib) and FHD-286 or OTX015 and FHD-286 significantly reduced the in vivo AML burden and improved survival of the immune depleted mice, without inducing significant toxicity, in the xenograft models of MITR and MI-resistant PD MLL1-r AML cells. These findings highlight novel, targeted, drug combinations that overcome MI resistance in AML cells with MLL1-r or mtNPM1.