Positive topline data from phase II clinical trial of olutasidenib in R/R AML

On October 26, 2020, positive topline results from a planned interim analysis of a phase II clinical trial of olutasidenib were announced.¹

Olutasidenib is a selective inhibitor of mutated isocitrate dehydrogenase 1 (IDH1) enzymes. IDH1 mutations occur approximately in 6-8% of patients with acute myeloid leukemia (AML). Olutasidenib is currently under evaluation in a phase I/II, multicenter, open-label study (NCT02719574) in patients with relapsed/refractory (R/R) AML or myelodysplastic syndromes (MDS) with an IDH1 mutation. The aim of the study is to evaluate the safety, efficacy, and pharmacokinetics/pharmacodynamics of olutasidenib in these patients.¹

The phase I stage of the trial was a dose escalation and expansion study of olutasidenib alone or in combination with azacitidine.

The phase II study includes eight different cohorts and will evaluate olutasidenib alone or in combination with azacitidine in various AML/MDS populations. The primary efficacy-evaluable population included 123 patients with R/R AML, who received olutasidenib as monotherapy (150 mg two times a day) at least six months before the interim analysis cut-off date of June 18, 2020. The primary endpoint of the phase II part is complete remission (CR) plus complete remission with partial hematological recovery (CRh).¹

Olutasidenib achieved a composite CR rate of 33.3% (30% CR plus 3% CRh). The median duration of CR/CRh has not been reached, but sensitivity analysis indicates a median duration of 13.8 months. The safety profile is consistent with previous phase I data, with the most common adverse events being nausea, fatigue, constipation, increased white blood cell count, decreased red blood cell count, fever, and febrile neutropenia.

Olutasidenib showed good preliminary efficacy and tolerability and could represent a promising therapy for patients with R/R IDH1-mutated AML. The phase II trial is currently ongoing and additional data are expected to be presented at upcoming congresses.