EHA 2021 | FF-10101-01: a novel FLT3 inhibitor for R/R AML
Mark Levis, MD, PhD, Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD, gives an update on the Phase I trial (NCT03194685) investigating the use of an FMS-like tyrosine kinase 3 (FLT3) inhibitor, FF-10101-01, to treat patients with relapsed or refractory (R/R) acute myeloid leukemia (AML). The aim of the trial was to establish a safe, tolerable dose and determine the efficacy of FF-10101-01 in gilteritinib-resistant patients. Dr Levis also discusses the difficulties of recruiting a large patient cohort who meet the trial requirements. This interview took place at the virtual European Hematology Association (EHA) Congress 2021.
Transcript (edited for clarity)
The reason for doing this follow-up data is, when we did the primary analysis, we actually had to sensor quite a few patients and we didn’t have long-term follow-up. And looking at the survival curves for the admiral trial, it was perfectly obvious that the study drug gilteritinib, the FLT3 inhibitor was clearly superior to salvage chemotherapy for relapsed/refractory FLT3 mutated AML but there was sort of a discouraging- everybody looked like they were eventually, potentially going to die because the survival curve kept going down...
The reason for doing this follow-up data is, when we did the primary analysis, we actually had to sensor quite a few patients and we didn’t have long-term follow-up. And looking at the survival curves for the admiral trial, it was perfectly obvious that the study drug gilteritinib, the FLT3 inhibitor was clearly superior to salvage chemotherapy for relapsed/refractory FLT3 mutated AML but there was sort of a discouraging- everybody looked like they were eventually, potentially going to die because the survival curve kept going down. But part of that was really a reflection of censoring.
And so, by carrying the analysis out, two years after the primary analysis, you can really start to see were there’re long-term survivors in patients treated with gilteritinib? And the short answer is yes, there were, there was a very reassuring plateau, which has kind of shown in the poster in some of the Kaplan Meier curves. We’re focusing on, I think 49 patients in the gilteritinib arm and 14 in the arm that was randomized to salvage chemotherapy. This is a collection that was alive two years after randomization. And then we really wanted to show that, look, there is a plateau in survival, it stops going down. They don’t all die. They, in fact, it looks like you can probably save these patients. We all have some of them, they’re essentially cured. I’ve got some that are alive right now, and for all intents and purposes are cured. And that’s kind of the big picture.
The other point, another interesting point was this business of taking patients to transplant. I think that’s actually shown in figure four of the poster. There was a criticism that, for a lot of regulatory agencies that, well, you’re just casually transplanting these patients cause you can. Your drug didn’t really do that, it was the transplant. But in fact, the comparison between the two arms, salvage chemotherapy and gilteritinib, if somebody got a response with either of those agents and went to transplant, they did the same. So, it wasn’t that gilteritinib was disguising patients and we took them to transplant and that was conferring all of the benefit. So really, it was not a fair criticism to say that gilteritinib was just allowing us to mask benefit with transplant. So again, this just kind of cements the deal that gilteritinib really was better than salvage chemotherapy. We have good follow-up that shows that benefit persisted.
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