ASH 2025 | Olutasidenib with co-targeted therapy in R/R IDH1-mutated myeloid malignancies: Phase II trial

So this is a Phase II trial that we recently opened at MD Anderson Cancer Center and hoping to open at some other sites as well. But what we’re really trying to do is when we look at a lot of the studies on patients with IDH1-mutated AML and we’re using the targeted therapies to treat them, we’re seeing a lot of emergence of signaling mutations at relapse, particularly using single-agent ivosidenib, as well as in the VIALE-A trial, we’re seeing the emergence of FLT3 and RAS mutations in those patients. And what we were really trying to do with this trial was see if we can use co-targeting agents to target both of those pathways. So it is a trial in relapsed/refractory patients with either high-risk MDS or AML. And what we’re doing is there’s three different arms for patients. So you have to have an IDH1 mutation, and then you also have to have a co-signaling mutation either in the RAS MAP kinase pathway or in the FLT3 pathway or JAK2 mutated. And we’re combining olutasidenib with cladribine low-dose cytarabine for those that are RAS mutated, and then combining olutasidenib with gilteritinib if you’re FLT3 mutated, and then combining it with a JAK inhibitor, ruxolitinib, if you have a JAK2 mutation. And again, the hope is to kind of target the resistance mechanisms to hopefully improve outcomes for these patients.

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