DR STONE: The slide depicts that its advantages compared to quizartinib, if you will, is that it also hits the D835 “wire,” the D835 mutation, which means it’s likely to work in a slightly wider spectrum of patients than is quizartinib. Moreover, a lot of the patients who get quizartinib become resistant, because they grow out a clone with a point mutation in D835 mutation patients. So that has that advantage.

It’s relatively inactive against c-KIT. So it’s a specific FLT3 inhibitor that has some similar, I would say, single-agent response data that we saw with quizartinib, that has a few theoretically improved properties.

This is a recent abstract from Mark Levis talking about how the “CRC” rate is 52%. Ironically, it’s the same as it was with quizartinib, about 53%. So it’s hard to know which of these 2 agents is better at the moment — probably this one.

DR LOVE: Jorge, what about the issue of response based on type of alteration, at least that was seen here with gilteritinib?

DR CORTES: Yes, this is important, because, as Rich mentioned, one of the mechanisms of resistance to some of the FLT3 certainly has been reported with sorafenib and with quizartinib, is the emergence of the D835 mutation. That’s been shown in vitro. Neil Shah and others have shown that. And we’ve shown that about 20% to 25% of the patients who are treated with these drugs develop resistance through the emergence of these mutations.

And this drug, because it has activity against this mutation, and you see some responses with that. So it has that advantage. It also hits, by the way, this mutation, “F6919L,” which is the gatekeeper mutation. All the kinases that have kinase inhibitors, they have these gatekeeper mutations, like the T315I for BCR-ABL, et cetera. And this drug does inhibit that.

So in theory, they would be less prone to develop resistance through these mechanisms. Again, we mentioned earlier, AML is a very molecularly heterogeneous disease. So that may not be the only way that cells can develop resistance. But at least in principle, this drug, because of this preclinical and clinical — as we can see on this slide — activity against the D835, it would be less prone to this particular mechanism of resistance.

Module 1: Current and future approaches to targeted therapy for acute myeloid leukemia (AML)

Module 2: Other clinical issues in AML management

Module 3: Case discussions