Dr Winer on the Efficacy of Emavusertib in AML With FLT3 and Spliceosome Factor Mutations

“Emavusertib may be able to not just hit the bypass mechanisms for the previous diseases, but may have higher efficacy compared with the other FLT3 inhibitors that patients were already refractory to.”

Eric S. Winer, MD, clinical director, Adult Leukemia, Dana-Farber Cancer Institute; and assistant professor, medicine, Harvard Medical School, discusses top data from the ongoing phase 1/2 TakeAim Leukemia trial (NCT04278768) investigating the oral small molecule IRAK4 inhibitor emavusertib (CA-4948) in patients with relapsed/refractory acute myeloid leukemia (AML) harboring FLT3 and/or spliceosome factor mutations.

Of 19 evaluable patients with relapsed/refractory FLT3-mutated AML who had received 2 or fewer prior lines of therapy and received treatment with emavusertib at the recommended phase 2 dose of 300 mg twice daily, 6 patients had a complete remission (CR), 2 had a CR with either a CR with incomplete hematological recovery (CRi) or a partial hematological recovery, and 2 had morphologic leukemia-free state. These data further highlight the efficacy of emavusertib monotherapy, Winer says. Notably, 2 patients who achieved a CR and a CRi, respectively, subsequently underwent allogeneic stem cell transplantation.

A key finding from the trial was that most patients with FLT3-mutated AML had previously received FLT3 inhibitors, such as midostaurin (Rydapt) or gilteritinib (Xospata), many of whom still responded to emavusertib, Winer emphasizes. This suggests that emavusertib may effectively overcome resistance mechanisms associated with previous FLT3 inhibitors and may exhibit higher efficacy in this refractory population, he explains.

Patients with spliceosome factor mutations also achieved clinical responses with emavusertib, although its efficacy was less pronounced than in the cohort of patients with FLT3 mutations, Winer notes. Responses, including cCRs, were also observed in the spliceosome factor mutation subgroup, Winer states. Most of these patients had prior exposure to hypomethylating agents plus venetoclax (Venclexta), indicating that emavusertib may provide therapeutic benefits even in heavily pretreated populations, he concludes.