Gilteritinib is a FLT3 inhibitor that was developed and inhibits both the FLT3 internal tandem duplication mutation and the tyrosine kinase domain mutation. Based on its activity in the lab it was brought forward into a phase I/II clinical trial that was named the CHRYSALIS study.

We’re talking about the deep molecular response that was observed.

At the European Haematology Association meeting we presented data on the results of gilteritinib in FLT3 ITD mutated patients and assessing the molecular responses that occurred. We found that a portion of patients developed a deep molecular response and the achievement of a deep molecular response was associated with an improvement in survival compared to those who did not attain that response. This is the first time that molecular remissions have been reported in patients treated with FLT3 inhibitors.

One of the measures for this was the ITD signal ratio, if you could explain how this was measured.

This is done by Invivoscribe, another company, and assessing the wildtype and mutant allele burden. They have software using next generation sequencing with an Illumina platform assessing the relative frequency of the ITD and the wildtype alleles. They are able to have very deep sensitive assessment, down all the way to 10-4.

Impressive. When outcomes from looking at not just the deep molecular response but going forwards to patient outcomes, how did that affect median overall survival?

Patients who attained a molecular response defined as either 10-2, 10-3 or 10-4 had an improvement in survival by a Kaplan-Meier assessment compared to those who didn’t. There were a total of 80 patients who we were able to assess who had obtained FLT3 levels at baseline and at one or more time points on this study. Those who obtained this molecular response had an improvement in survival compared to those who didn’t.

Can we take these results as possibly a prediction for a phase II, phase III study if they’re to be repeated?
It’s an area definitely worthy of more study. What’s exciting about this is that we’ve demonstrated that patients who are treated with a FLT3 inhibitor can attain a molecular response and if you have a molecular response you have an improvement in survival. But certainly this needs to be compared. There are currently two ongoing studies with gilteritinib in maintenance therapy looking at MRD assessments.

I don’t suppose you know the name of those trials off hand?

I can get them to you; I don’t.

Do you have any plans for expansion or further studies of your own?

The subset that we were able to look at in the data that I presented at EHA only evaluated about 51%, half of the patients on the trial, who were treated in the dose cohorts that we looked at. So we want to be able to look at all of the patients, so finish collecting all of that data. This sets the platform for when patients are treated with targeted therapies being able to follow molecular assessments.