Menin Inhibitor Study Results: Ziftomenib for Newly Diagnosed AML Patients | Amer Zeidan, MBBS | #ASH24

Yeah. Hi. My name is Amer Zeidan and I’m a professor of medicine and the chief of hematologic Malignancies division at Yale University. And it's a pleasure to be here with you from San Diego, where I'm actually at the American Society of Hematology annual, meeting. So a lot is happening on the front of all cancer blood cancers. But my focus today is actually on acute myeloid, leukemia, where a lot of data has been presented.

One of the presentations, which I did on behalf of, the group of investigators, looked at the use of one of the novel Menin inhibitors called Ziftomenib. So we presented data combining Ziftomenib with seven plus three, which is an intensive chemotherapy. The standard approach that we used to treat patients with acute myeloid leukemia. But based on very nice data for the Ziftomenib, which is an oral pill given once a day, as a single drug given in patients with advanced leukemia, we took the next step, which what we usually do on oncology.

When you have a good drug that is active, you try to combine it in earlier lines of treatment with the other standard of care drugs. So this is what we did here, where we added this ziftomenib up to the intensive chemo. And we treated 51 patients on a phase one trial using increasing doses of the ziftomenib.

And what we have, demonstrated is that the combination does not seem to add to the adverse events that you typically see from the intensive chemo by itself. So it was well tolerated. And we also have shown that, the preliminary evidence of efficacy among the patients who had NPM1, was actually quite good with all the patients, all 24 patients achieving complete response.

And the patients who had KMT2A mutation, arrangement, which is, difficult to treat, a translocation, the response rate was 87%. So I think the data is very encouraging. And based on this, there is a large phase three trial that will be conducted to look at the use of intensive chemo and azacytidine and venetoclax in combination with ziftomenib, which hopefully will register the drug for the frontline indication.

So menin inhibitors are a new group of very exciting drugs, what we call targeted therapies. So they are pills that are taking basically with for patients with acute myeloid leukemia, that target specific alteration that occurs in around 40% of patients. And the two main genetic alterations are, a mutation in a gene called NPM one, as well as a rearrangement in another gene called KMT2A.

Between these two, around 40% of patients will have one of those alterations. And this follows on the path of other targeted therapies that we have used in AML, such as IDH inhibitors and FLT3 inhibitors. So those are not chemo therapies. Those are targeted agents that are customized basically for that specific genetic alterations that patients have. So there is a number of those menin inhibitors.

And, it's always a good, option to have multiple choices for, for the patients. Those, drugs are in different stages of development. Some of them are being tested as single drug, as a monotherapy. Some of them are tested in combination. And I think, the field is clearly very excited that the entire session of six different talks were basically focused on different menin inhibitors.

So very exciting time, to kind of explore new drugs.