Table 1.
Key Features of Menin Inhibitors with Reported Clinical Trial Results in R/R Acute Leukemias
| Significant CYP3A4 Inhibition | Differentiation Syndrome | QTc Prolongation | ORR (CR + CRh + CRp + CRi) | |
|---|---|---|---|---|
| Revumenib [46, 47](SNDX-5613) | Yes | 26.6% in phase 2 | 23.4% in phase 2 | 53% in phase 1 (KMT2Ar and NPM1m) 43.9% in phase 2 (KMT2Ar) |
| Ziftomenib [51](KO-539) | No | 29% in phase 1b | 0% phase 1a or 1b | 33% at 600 mg dose of phase 1b (KMT2Ar and NPM1m) |
| DSP-5336[56] | Yes | Possibly 1/24 (4%) in phase 1, but attribution difficult | 0% in phase 1 | 33% among 6 patients treated on phase 1 at doses projected to be effective (KMT2Ar and NPM1m) |
| Bleximenib (JNJ-75276617) [59] | No | 14% in phase 1 | 1% reported in phase 1 | 35% in patients treated at higher dose levels in phase 1 (n = 20) (KMT2Ar and NPM1m) |
| BMF-219[63] | Yes | 13% in phase 1 | 0% reported in phase 1 | 2 out of 5 efficacy evaluable patients in phase 1 (40%) (KMT2Ar and NPM1m) |
CYP3A4, cytochrome P450 3A4; QTc, QT interval corrected for heart rate; ORR, overall response rate; CR, complete remission; CRh, complete remission with partial hematologic recovery; CRp, complete remission with incomplete platelet recovery, Cri, complete Remission with incomplete count recovery; KMT2A, histone-lysine n-methyltransferase 2A; NPM1 Nucleophosmin 1