Dr Winer on the Rationale for the TakeAim Leukemia Trial in Mutated AML

Eric Winer, MD, clinical director, Adult Leukemia, institute physician, Dana-Farber Cancer Institute; assistant professor, medicine, Harvard Medical School, discusses the rationale for the phase 1/2a TakeAim Leukemia trial (NCT04278768) investigating emavusertib (previously CA-4948) in patients with relapsed or refractory FLT3- and spliceosome-mutated acute myeloid leukemia (AML), as well as key efficacy findings from this study.

Notably, data from the investigation were presented at the 2024 ASCO Annual Meeting. The TakeAim Leukemia trial was designed to determine the effectiveness of IRAK4 inhibition in promoting cell death in AML cells and high-risk myelodysplastic syndrome cells, Eric begins. This trial focused on 2 patient populations: those with FLT3 mutations and those with spliceosome mutations, he states. Treatment with emavusertib in patients with mutated AML reportedly demonstrated anti-leukemic activity and exhibited a manageable safety profile. The encouraging aspect of the TakeAim Leukemia trial is that its results aligned with expectations based on preclinical data, demonstrating that the drug performed as anticipated, Winer reports.

In practical terms, more than 50% of patients experienced a reduction in blast counts, with significant responses observed in the FLT3-mutated and spliceosome-mutated groups, Winer expands. This finding confirmed the study’s hypothesis and demonstrated a clear antileukemic effect with the agent, paving the way for further trials, he states. Additionally, in the FLT3-mutated disease group, the IRAK4 inhibitor was effective against both FLT3 ITD and TKD mutations. Among the 12 patients treated within the FLT3-mutated subgroup, 6 patients experienced responses, and 4 patients achieved complete remission (CR) or CR with incomplete blood count recovery, Winer emphasizes.

These results illustrate a targeted effect of the IRAK4 inhibitor, highlighting its potential benefit for patients with specific genetic mutations, he says. The trial’s success in proving the mechanism of action and efficacy of emavusertib offers promising implications for future therapeutic strategies and trials, Winer concludes.