ASH 2024 | The KOMET-007 trial: ziftomenib plus intensive chemotherapy to treat AML

So, ziftominib is a drug that belongs to a group of drugs called menin inhibitors. Those, I think, are some of the most exciting new agents in the management of patients with acute myeloid leukemia. So, ziftominib seems to work primarily on two mutations, which are NPM1 mutation, as well as a rearrangement called KMT2A, which used to be called MLL. So around 40% of patients with acute myeloid leukemia will have one of those alterations. And those drugs, including ziftominib and a number of other similar agents, were tested first as single agents in refractory and relapse acute myeloid leukemia and have led to, I think, important responses. However, the responses were somewhat limited as you’d expect in patients with relapse and refractory leukemia. And what we presented in this meeting is I think the next step which is trying to combine these promising drugs with intensive treatment or AZA-VEN which are the standard treatments that we use for patients with acute myeloid leukemia. So specifically the presentation called of a study called KOMET‑007 which is a Phase I study that included patients who received intensive chemo 7+3 as long as they had one of those two genetic alterations in addition to ziftominib. And in this study we have done what we call a dose escalation we went from ziftominib 200, 400, 600 and we included a total of 51 patients in both KMT2A rearranged patients as well as NPM1 mutated patients. And I think it was clear from our data that there was no evidence of increased toxicity beyond what we typically see with 7+3. There was only one case of differentiation syndrome which was well mitigated and there were no dose limiting toxicities or zifto-related QTc prolongation. So I think the safety profile was good. What was very impressive is the response rate as well. So the response rate in the NPM1 mutated patients, there were 23 of them who were response evaluable, was 100%. All the patients achieved complete remission. And in the patients who had the KMT2A rearrangement, around 87% achieved complete remission. So very promising responses. We are looking forward to following this data for longer term. But based on this very promising data, a Phase III trial, which will be a registration intent both with intensive chemo and in combination with AZA, is going to launch next year. We are hoping that this treatment will become a standard treatment and change the phase of how we treat patients with acute myeloid leukemia.

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