ziftomenib + elacestrant

**Ziftomenib + elacestrant** is a combination of two targeted small molecule drugs investigated for potential synergistic activity in oncology, particularly in acute myeloid leukemia (AML). Ziftomenib (KO-539) is a potent, selective inhibitor of the menin-MLL interaction, disrupting the menin-MLL(KMT2A) complex critical for leukemogenic transformation in NPM1-mutated or KMT2A-rearranged AML, leading to differentiation, apoptosis, and anti-proliferative effects. Elacestrant (Orserdu) is an oral selective estrogen receptor degrader (SERD) that antagonizes estrogen receptor alpha (ERα), inducing degradation and inhibiting ER signaling, primarily approved for ER-positive/HER2-negative advanced breast cancer post-endocrine therapy and CDK4/6 inhibitors. Developed by Kura Oncology (ziftomenib) and Stemline Therapeutics/Menarini (elacestrant), this pairing leverages ziftomenib's chromatin-modulating effects with elacestrant's hormonal pathway inhibition, though no published clinical trials specifically evaluate this combination; preclinical synergy data for ziftomenib exists with other agents like venetoclax, suggesting potential for combinations targeting apoptosis or chromatin regulation.[1][5]