Ziftomenib Combination Delivers Deep Responses in R/R AML

In an interview with Targeted Oncology, Eunice S. Wang, MD, of Roswell Park Comprehensive Cancer Center, reviewed the efficacy and safety findings from 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).

Wang highlights the encouraging clinical activity observed with the combination regimen, which achieved an overall complete remission with or without complete hematologic recovery (CRc) rate of 48%, with approximately two-thirds of responders achieving minimal residual disease (MRD) negativity. She emphasizes that the greatest benefit was seen among patients who had not previously received venetoclax-based therapy. In this subgroup, the overall response rate exceeded 80%, the CRc rate reached 70%, and roughly three-quarters of responding patients achieved MRD-negative remissions. By comparison, patients with prior venetoclax exposure experienced substantially lower response rates, with a CRc rate of 24%.

In terms of safety, Wang explains that the combination was generally well tolerated, with hematologic toxicities such as neutropenia, febrile neutropenia, and low blood counts occurring at expected rates for this treatment setting. Notably, differentiation syndrome—a known adverse event associated with menin inhibitor therapy—occurred in only 2 of 67 patients. Both cases were grade 3 but were successfully managed using protocol-specified interventions.

Finally, Wang discusses the improvement in response durability observed with the combination approach. Compared with ziftomenib monotherapy, the median duration of response increased from approximately 4 months to 8.6 months, supporting the potential of ziftomenib plus venetoclax and azacitidine to enhance outcomes without substantially increasing treatment-related toxicity for patients with R/R AML.