Stéphane de Botton, MD, PhD, Gustave Roussy Institute, Paris, France, shares the findings of the interim analysis of a Phase II study (NCT02719574) of olutasidenib, a small molecule inhibitor of mutant IDH1, for patients with relapsed/refractory (R/R) mutant-IDH1 acute myeloid leukemia (AML). At the time of analysis, 153 patients were evaluable for efficacy, of which 72% had discontinued treatment with olutasidenib, primarily due to disease progression (31%). The overall response rate was 46% with a median duration of 11.7 months. The complete response rate was 30% with median duration not reached. Dr de Botton discusses these results and gives an overview of their clinical implications. This interview took place at the virtual European Hematology Association (EHA) Congress 2021.
Transcript (edited for clarity)
The results we presented are the results of a Phase II multicenter international trial evaluating olutasidenib as a single agent in relapsed/refractory AML patients. So, this is a cohort, the results of cohort one, in which 153 patients with relapsed/refractory AML received olutasidenib alone at the dose of 150 milligrams BID over continuous 28-day cycles and the primary endpoint was characterization of CR and CRh...
The results we presented are the results of a Phase II multicenter international trial evaluating olutasidenib as a single agent in relapsed/refractory AML patients. So, this is a cohort, the results of cohort one, in which 153 patients with relapsed/refractory AML received olutasidenib alone at the dose of 150 milligrams BID over continuous 28-day cycles and the primary endpoint was characterization of CR and CRh.
Altogether, 123 patients were evaluable for efficacy. 72% of these continued mainly due to disease progression -roughly one third – a few to AEs or death. So, as expected, the population was mainly represented by de novo AML. Roughly two third and one third of secondary AML, including almost 80% post-MDS. Most had intermediate risk cytogenetics and co-mutations free, so, NPM1 first with DMT3A and, and other.
So, overall response were achieved in 46 persons of these patients, which is fairly high composite CR rate, including CR/CRh, CRi or 45. 33% achieved CR/CRh, and importantly true CR happen in 30% of the patients. So, these results are probably very good, especially the high CR rates in that widely treated population. They received a median of at least two lines of treatment.
Before discussing optimization, I must insist in the fact that these responses were durable. Responses were sustained for a median of 11.77 month in responders, and remarkably, so, the median duration of responses in CR CRH was not reached and in a sensitivity analysis with stem cell transplant as the end of of a response, indicates the median duration of CR/CRh to be roughly 14 months. So, that’s very important. These responses are durable. So, this translates into a very favorable overall survival with estimated 18-month overall survival of 87% in CR/CRh patients, which is fairly high.
So, this is interesting because the inhibitor seems to be very potent to ensure higher response rates and durable responses. So, the combination with Vidaza has already been presented two years ago at ASH in the Phase I part of the trial and it’s very well tolerated. We haven’t seen any addition of toxicity with the inhibitor combined with Vidaza so it’s really, it’s clearly feasible. In the Phase II, there are some arms combining the treatment Vidaza and olutasidenib, so it’s feasible. We are waiting for combination with intensive chemotherapy. It’s probably slightly, that will be the same development as with ivosidenib.