ASH 2024 | Bleximenib dose optimization from a Phase I trial in patients with R/R acute leukemia

The abstracts I presented on Saturday at ASH 2024 outlined what we know to be the correct dose to take forward of bleximenib, which is a novel menin inhibitor used for patients with relapsed refractory acute leukemias. I described really how we determined that dose. So we initially treated 146 patients across a range of dosing levels. And I presented the findings ranging from 45 milligrams twice daily through to 150 milligrams twice daily. And then so we used all of those patients to establish the safety profile of the drug. The majority of those patients had acute myeloid leukemia. There were a few patients with acute lymphoblastic leukemia or other acute leukemias. And in the safety portion of the study, what we found out was that overall the drug is very tolerable, although there is a particular side effect called differentiation syndrome, which we know is a class effect now across all of the menin inhibitors. And this is a side effect that you do need to take care of when you’re initiating therapy or dose escalating. And we saw a 14% differentiation syndrome rate. Most of this was mild and there were mitigation measures implemented in the study to manage this side effect, which appeared to be effective. But sadly, early in the study, we did have two patient deaths with differentiation syndrome. So it’s certainly a side effect that has to be watched. We’re aware that with some of the other menin inhibitors, you can see QTc prolongation, and we didn’t see any QTc prolongation with bleximenib, which makes the drug a bit easier to manage. And then moving on to the efficacy subpopulation. So this concentrated in on 52 patients who had received a dose range within the efficacious range but who had also got one of two defining genetic abnormalities, so either a KMT2A rearrangement or an NPM1 mutation. And looking at the efficacy across all of those cohorts, we were able to establish that the correct dose was 100 milligrams twice daily with a 50 milligram twice daily two week step up period and at that level the overall response rate was 47.6 percent with a CR CRh rate of 33.3 percent and the responses looked pretty evenly split across the NPM1 mutated patients and KMT2A rearranged patients. So that we said it’s very early study and it’s very immature data, but the duration of response across all of the patients assessed in the dose optimisation cohort was around about six months. So exciting to have another tool in our armoury for the management of acute myeloid leukaemia. There’s ongoing studies, obviously, both with bleximenib and other agents in combination with standard treatments for acute leukemia and so I look forward to seeing how the field develops.

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