Ziftomenib Combo Shows Frontline Potential in AML

In an interview with Targeted Oncology, Amer Zeidan, MBBS, MHS, chief, division of hematologic malignancies at Yale Cancer Center and professor of medicine at Yale School of Medicine, discusses efficacy and safety findings from the phase 1b/2 KOMET-007 trial (NCT05735184) evaluating ziftomenib (Komzifti) in combination with standard 7+3 induction chemotherapy for patients with newly diagnosed NPM1-mutated or KMT2A-rearranged acute myeloid leukemia (AML), presented at the 2026 European Hematology Association (EHA) Congress in Stockholm, Sweden.

Watch the first part of Dr Zeidan’s interview.

According to Zeidan, the combination demonstrated a favorable safety profile, with adverse events generally consistent with those expected from intensive induction chemotherapy alone. The most common toxicities included myelosuppression, infection, and bleeding, while rates of differentiation syndrome and QTc prolongation remained low and manageable. Importantly, investigators did not observe evidence of prolonged myelosuppression, with platelet and neutrophil recovery occurring within the timeframe typically seen with standard 7+3 therapy.

Zeidan also highlights encouraging efficacy outcomes from the study. Composite complete response rates exceeded 90% in both molecular subgroups, reaching 96% among patients with NPM1-mutated AML. Most responding patients achieved measurable residual disease (MRD) negativity by central assessment, suggesting deep and durable remissions.

The study also demonstrated promising early survival outcomes. At a median follow-up of 17 months, the 12-month overall survival rate was 94% among patients with NPM1-mutated AML and 71% among those with KMT2A-rearranged disease. While median overall survival has not yet been reached, Zeidan notes that many patients remain on study treatment, and longer follow-up will help clarify the durability of responses.

He also discusses the ongoing phase 3 KOMET-017 (NCT07007312) registrational program, which is evaluating ziftomenib in combination with both intensive and nonintensive frontline AML treatment approaches.