Advancing Menin Inhibition in Relapsed/Refractory AML

In an interview with Targeted Oncology, Eunice S. Wang, MD, of Roswell Park Comprehensive Cancer Center, discussed the rationale and design of the phase 1/2 KOMET-007 trial (NCT06097832) evaluating ziftomenib (Komzifti) in combination with venetoclax (Venclexta) and azacitidine for patients with relapsed or refractory acute myeloid leukemia (R/R AML).

Ziftomenib is a menin inhibitor approved for patients with R/R NPM1-mutated AML. Although ziftomenib monotherapy demonstrated clinically meaningful activity in this molecularly defined patient population, Wang explains that they sought to improve upon these outcomes by combining the agent with established treatment backbones.

Wang focuses on the venetoclax-azacitidine cohort of KOMET-007, which enrolled 67 patients with R/R AML. She describes the study's dose-escalation phase, during which patients received ziftomenib at doses ranging from 200 mg to 600 mg to identify the optimal dose for combination therapy. Based on the safety profile and encouraging clinical activity observed, investigators selected 600 mg as the recommended dose, followed by enrollment of an expansion cohort treated with ziftomenib 600 mg plus venetoclax and azacitidine.

Throughout the interview, Wang discusses how the combination strategy builds on the efficacy demonstrated with ziftomenib alone and the potential for menin inhibitor–based regimens to further improve outcomes for patients with R/R NPM1-mutated AML. She also explains the significance of the dose-selection process and the role these findings may play in shaping future treatment strategies for this challenging disease.