EHA 2023 | LBA: KOMET-001 – ziftomenib monotherapy in R/R NPM1-mutated AML

At the late-breaking oral abstract session on Sunday, my colleague Amir Fathi and coauthors, including myself, will be presenting the results of a Phase Ib study of a novel menin inhibitor, ziftomenib, for the treatment of relapsed and refractory NPM1-mutant AML. The results of the Phase Ib study encompass outcomes and safety and tolerability in 20 relapsed/refractory NPM1 patients, heavily pretreated with the median of three prior therapies. These particular patients are expected to have a very, very poor outcome, with survival measured in months. What we saw on these patients is that ziftomenib, 600mg a day, was very well tolerated. Differentiation syndrome was manageable with mitigation strategies, with only one patient developing a grade three and all other instances of differentiation syndrome and being grade two or less. Most impressively, we saw an overall response rate of 45% – almost half of patients getting clinical benefit with the drug, with 35% of patients developing a true CR with full count recovery. These results are the highest response rate that we’ve seen in this particular molecular subset of AML and suggest that further development of this drug for this particular subset of patients may be very viable in the near future.