FDA lifts partial clinical hold on phase I/II TakeAim Leukemia trial of emavusertib in patients with AML and MDS

On July 6, 2023, the U.S. Food and Drug Administration (FDA) lifted the partial clinical hold on the phase I/II TakeAim Leukemia trial (NCT04278768), which the AML Hub has previously reported findings from.¹ This trial evaluated emavusertib, an orally available, small molecule triple target inhibitor of IRAK4, FLT3, and CLK, which was granted orphan drug designation by the FDA as a treatment for patients with acute myeloid leukemia (AML) or myelodysplastic syndromes.¹  

On April 4, 2022, the FDA initiated a partial clinical hold on the trial following the death of a patient with relapsed/refractory (R/R) AML who experienced rhabdomyolysis, a previously identified dose-limiting toxicity.² The FDA requested data on safety and efficacy, as well as data related to rhabdomyolysis and the determination of the recommended phase II dose (RP2D).² On August 30, 2022, the FDA announced that the enrollment of additional patients in the monotherapy phase (phase Ia) could continue, whilst the partial hold remained for the combination therapy phase (phase Ib) and the expansion phase (phase IIa) until the completion of phase Ia and approval from the FDA.³

As of March 17, 2023, 84 patients received emavusertib monotherapy in the TakeAim Leukemia trial.¹ Doses ranged from 200–500 mg twice daily. Emavusertib was associated with blast count reductions in all patient groups, independent of dose level, mutational status, and number of prior lines of therapy. Promising responses to emavusertib monotherapy have been observed in R/R patients with FLT3-mutated AML and R/R patients with U2AF1- or SF3B1-mutated AML who received ≤2 prior lines of therapy. The RP2D has been identified as 300 mg twice daily.¹