ASCO 2026 | Insights into a Phase Ib/II trial of azacitidine, venetoclax, and ivosidenib in IDH1-mutated AML

So just to give a quick overview of this trial to start for background. So for our patients with IDH1-mutated AML who are unfit for intensive chemotherapy, we currently have two standard of care regimens available. So there’s azacitidine and venetoclax, or there’s azacitidine and ivosidenib. And while outcomes for those two doublets have been fairly good, patients still, there’s a significant proportion of patients who don’t respond or eventually relapse. And so the goal of this trial was really to combine each of those agents together into a triplet regimen to see if that could improve outcomes. And so this was a multicenter investigator-initiated trial combining each of these three agents. And the data that we were presenting here was looking at the complete enrollment of the newly diagnosed AML cohort. So we had 40 patients enrolled from a total of four different sites. And really encouragingly, we found that the overall response rate with this triplet regimen was 95%, with 93% of patients achieving a composite complete remission. Furthermore, MRD negativity by flow cytometry was achieved in 91% of evaluating responders. We now have about three years of follow-up, and we still have not reached the median overall survival or duration of remission in these patients. So at three years, the overall survival was just about 80%, and we’ve only had three patients relapse to date. 

In terms of safety and tolerability, we really haven’t seen any new or unsurprising safety signals. Most of the adverse events experienced were a grade one or grade two. There were two patients that had QTc prolongation, which was kind of attributed to the ivosidenib, but with a dose reduction, were able to successfully continue on that therapy. There was only one case of grade four differentiation syndrome. Again, with kind of supportive care measures, steroids, hydroxyurea, patients were able to successfully resume treatment. And there were no deaths within the first two months of therapy. And we were able to get a little over half of… 18 of the 40 patients were able to proceed to transplant. And so when we’re really looking at safety and tolerability, one of the things we look at is how many patients are still on study. And so there are currently 12 patients, which is 55% of patients that did not go to transplant that are still on study. And there are now patients who have been on therapy for over six years. And so we really, in the conclusions from the study, we really think that it’s very promising results, really high MRD negative response rates, durable remissions, with really comparable safety to the doublets.

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