The IRAK-4 inhibitor emavusertib showed encouraging clinical activity in patients with higher-risk myelodysplastic syndromes (MDS), according to preliminary data from the phase 1/2 TakeAim Leukemia trial.
Results were presented in a poster session at the 66th American Society of Hematology (ASH) Annual Meeting and Exposition by Guillermo Garcia-Manero, MD, of the University of Texas MD Anderson Cancer Center.
Promising responses were observed in patients with spliceosome mutations, including U2AF1 and SF3B1, who had received fewer than three prior lines of therapy. Among 13 evaluable patients treated with 300 mg twice daily, four achieved marrow complete remission. Two additional patients in new seven- or 14-day dosing cohorts also achieved remission and remain on treatment, according to the investigators. Two patients across both groups proceeded to stem cell transplant.
Clinical responses were seen in patients with other high-risk mutations, including RUNX1, ASXL1, DNMT3A, TET2, and BCOR. Some had previously received venetoclax, and all had prior exposure to hypomethylating agents.
The treatment was generally well tolerated; Among 145 patients with relapsed or refractory acute myeloid leukemia or high-risk MDS treated at various dose levels, 28.3% experienced grade 3 or higher treatment-related side effects, most of which were reversible and manageable, Dr. Garcia-Manero and colleagues reported in the abstract.
Trials are ongoing to evaluate emavusertib as both a single agent and in combination with other therapies.
“Emavusertib demonstrated encouraging anti-cancer activity in [higher-risk] MDS patients dosed at 300 mg BID in continuous or [seven]- or 14-day dosing,” Dr. Garcia-Manero and colleagues wrote. “The mutation profiles of responders indicate that emavusertib may be able to target diverse underlying genetic mechanisms of resistance to VEN or HMA regimens.”
Reference
Garcia-Manero G, Sallman D, Tarantolo S. Preliminary safety, efficacy and molecular characterization in patients with higher-risk myelodysplastic syndrome treated with single agent emavusertib (CA-4948). Abstract 3225. Presented at the 66th American Society of Hematology Annual Meeting and Exposition; San Diego, California.
