Amer Zeidan, MBBS, MHS, Yale Cancer Center, New Haven, Connecticut, discusses the results from the KOMET-007 trial evaluating the safety and efficacy of ziftomenib, a highly selective menin inhibitor, in combination with intensive induction chemotherapy, cytarabine and daunorubicin, for the treatment of newly diagnosed acute myeloid leukemia (AML). 

These data were presented at the European Hematology Association (EHA) 2025 Congress in Milan, Italy. The results of this analysis demonstrated efficacy and safety for ziftomenib in combination standard with cytarabine and daunorubicin for patients who have newly diagnosed AML. 

Dr Zeidan stated, “The data certainly confirms the efficacy of this combination as well as the safety of the combination.”

Transcript:

Hi everyone. My name is Amer Zeidan. I'm a professor of medicine at Yale University and the Chief of Hematologic Malignancies Division at Yale Cancer Center. It's a true pleasure to join you today to talk about our recent study KOMET-007, which we presented at the EHA meeting that was held in Milan in June 2025.

The study looks at the combination of a menin inhibitor called ziftomenib. We know these menin inhibitors have shown very good activity as monotherapy. We already have one that's approved called revumenib. Those drugs as monotherapy generally lead to responses including complete responses that last generally several months. But in the relapsed/refractory setting, this has been always very challenging to have a cure or  durable responses. 

The goal was to try to combine ziftomenib with the standard therapies including azacitidine and venetoclax in patients with older unfit AML as well as with standard intensive chemotherapy, [the] 7 + 3 [regimen] in older fit patients. Of course, in this study we included patients who had NPM1-A mutation or KMT2A-R leukemia. Those are the 2 subsets that have shown the most likelihood to respond to menin inhibitors.

The update we provided in EHA of almost 80 patients at this point, [with] the focus on patients who have received intensive chemotherapy with ziftomenib with 7 + 3, and we have done a dose escalation, as well as a dose expansion. We have found that the dose of 600 milligrams of ziftomenib, which is given continuously, starting day 8 of induction, was the dose to be used in the expansion phase of the study. The responses that we have seen on the study, which is still ongoing, looked quite good. The CR rate was quite high, both for NPM1 as well as KMT2 rearranged leukemias. Many of the patients are still in remission and the survival follow-up is ongoing.

The data certainly confirms the efficacy of this combination as well as the safety of the combination. There were no QTc concerning symptoms as well as very limited differentiation syndrome. These are the kind of side effects we monitor for patients who receive menin inhibitors. 

Because of the success of the KOMET-007 phase 1 study, we are now launching a phase 3 study, called KOMET-017, which will be a registrational large international study that will include patients receiving 7 + 3 plus minus ziftomenib. But also, within the same study it is going to have a AZA-VEN plus minus ziftomenib. 

Those will be 2 large international studies within the same protocol, and hopefully they will lead to the approval of ziftomenib as an option for patients with NPM1 and KMT2 rearranged leukemia in the next years. Thank you so much for listening.

Source:

Erba H, Wang E, Fathi A, et al. Ziftomenib combined with intensive induction chemotherapy (7 + 3) in newly diagnosed NPM1-M or KMT2A-R acute myeloid leukemia (AML): updated phase 1a/b results from JOMET-007. Presented at EHA 2025 Congress. June 12-June 15, 2025; Milan, Italy. Abstract 4159213.