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ASH 2025 | Enzomenib monotherapy in R/R AML: updated results from a Phase I/II study
Naval Daver, MD, The University of Texas MD Anderson Cancer Center, Houston, TX, discusses the updated results from the Phase I portion of a Phase I/II trial (NCT04988555) investigating the menin inhibitor enzomenib in patients with relapsed/refractory (R/R) acute myeloid leukemia (AML). Dr Daver highlights the promising findings with this agent, suggesting that it may offer improved efficacy and a more favorable safety profile compared to currently approved menin inhibitors. This interview took place at the 67th ASH Annual Meeting and Exposition, held in Orlando, FL.
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Transcript
The menin inhibitors in general are a very hot topic last year and this year at ASH and I think will continue for some time. So this is a group of drugs that works in two specific subsets of AML: NPM1 mutated, which is quite common, about 25-30% of AML, and KMT2A rearranged AML. And we now have two menin inhibitors approved, ziftomenib and revumenib, and enzomenib is kind of a newer one that is being developed...
The menin inhibitors in general are a very hot topic last year and this year at ASH and I think will continue for some time. So this is a group of drugs that works in two specific subsets of AML: NPM1 mutated, which is quite common, about 25-30% of AML, and KMT2A rearranged AML. And we now have two menin inhibitors approved, ziftomenib and revumenib, and enzomenib is kind of a newer one that is being developed.
So we presented data of the completed phase one, which has 116 patients, so quite a good number of patients, of which about 65 patients had KMT2A rearranged NPM1 target population treated at what appeared to be the effective doses between 200 to 400 BID. We saw a good CR/CRh rate in the relapsed KMT2A at the recommended phase 2 dose. We’re seeing about a 40% CR/CRh rate, duration of remission of about 11 and a half months, median overall survival of 12 and a half months. This is very good when you compare it to the established approved menin inhibitors. We see CR/CRh rate of about 21 to 23%, duration of remission of four to six months and median survival of six to seven months, so almost double in terms of these parameters.
For relapsed NPM1, we’re still at the final dose optimization selection phase, but we’re again seeing a CR/CRh rate of close to around 44-45 percent, which is higher than the 20% to 25% that has been seen with revumenib and ziftomenib. And the duration of remission is about six months and ongoing. So we think that based on this, the efficacy of enzomenib is looking better than what has been presented and published with the prior menin inhibitors. And also, the safety is actually quite distinct. So, in terms of safety, enzomenib seems to have much less differentiation syndrome. The grade 3 is only 8%, less than 15%, 16% reported by others. And we actually have not seen any drug-related QTc prolongation. And it also has a very, very short half-life and no interaction with azoles. So, for all these reasons, we think that enzomenib may actually emerge as one of the best potential menin inhibitors in the clinical setting today. And because of that, it’s moving quickly into combinations with aza-ven and with gilteritinib. And some of that data was already presented this year at ASH. So, I think a very interesting drug in the menin space that we need to keep an eye on and hopefully see more data in the future with combinations.
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