EHA 2025 | Combining ziftomenib with chemotherapy for the treatment of AML: the KOMET trials

Menin inhibitors are among the most exciting drugs that we have for acute myeloid leukemia. We know that two particular subsets of patients with NPM1 or KMT2A rearranged leukemia tend to be more responsive to these drugs. There are a number of these agents that are in development. One of them has so far been approved, the revumenib, for KMT2A rearranged leukemia. But ziftominib has been studied extensively in NPM1 mutated AML and monotherapy data after refractory relapsed disease for AML is being presented in this meeting, as well as I think very nice data in the combination front. So updates from the Komet 007 by Dr Erba, the senior author on this paper, looks at the combination of ziftomenib with 7 plus 3. And we update the data that we presented in ASH 2024 from 40 patients to 80 patients. We continue to show that the combination is well-tolerated, that we don’t see evidence of added myelosuppression with ziftomenib. We don’t see evidence of concerning differentiation syndrome or QTc issues. So I think the combination is very well-tolerated. But most importantly, the efficacy, the CR rate is very high. Many patients will get MRD-negative CRs. So we are very excited for this data. And based on this, what we are also presenting in this meeting is the KOMET-017 study, which is a large registrational intent Phase III study that will look at adding ziftomenib to 7 plus 3, but also ziftomenib to AZA and VEN. So this will be effectively two studies in one. In the same protocol, will enroll intensive chemo candidate patients as well as unfit patients in the same protocol depending on the patient fitness. And the primary endpoint is going to be for the intensive chemo patients looking at MRD-negative CR plus event-free survival, while for patients who are unfit is going to look at CR plus OS. So there is an accelerated approval pathway built into these trials and we are very excited. We hope to get these Phase III ongoing very soon. And I think this is where you can see the full benefit of those menin inhibitors in combination early on because with monotherapy you see responses but they generally don’t last for a very long time, four to five months. But I think moving that to the frontline setting is where you can see hopefully overall survival improvement and major change in the patient outcomes.

This transcript is AI-generated. While we strive for accuracy, please verify this copy with the video.