Which Patients Stand to Benefit Most From Ziftomenib Triplet in AML?

In an interview with Targeted Oncology, Eunice S. Wang, MD, of Roswell Park Comprehensive Cancer Center, discussed which patients may benefit most from ziftomenib (Komzifti)-based combination therapy and how ongoing clinical trials could expand the role of the menin inhibitor in the frontline treatment of NPM1-mutated acute myeloid leukemia (AML).

Drawing on findings from the phase 1/2 KOMET-007 study (NCT06097832), Wang explains that the combination of ziftomenib, venetoclax (Venclexta), and azacitidine appears particularly effective in patients who have not previously received venetoclax. She notes that individuals who relapse after intensive induction chemotherapy without prior venetoclax exposure may represent an ideal population for the triplet regimen, given the high response rates observed in venetoclax-naive patients. Conversely, patients whose disease has already progressed on venetoclax and azacitidine may derive less benefit from simply adding ziftomenib, as they have already been exposed to 2 of the 3 agents in the regimen.

The conversation then shifts to the future development of ziftomenib. Wang discusses the rationale for evaluating the combination earlier in the disease course, particularly for older or medically unfit patients who are not candidates for intensive chemotherapy. The strong efficacy observed among venetoclax-naive patients suggests that adding ziftomenib to venetoclax and azacitidine in the frontline setting could improve outcomes compared with the current standard regimen alone.

Wang concludes by highlighting the ongoing phase 3 KOMET-017 trial (NCT07007312), which is comparing ziftomenib plus venetoclax and azacitidine with venetoclax and azacitidine alone in newly diagnosed, older, unfit patients with NPM1-mutated AML. She also discusses the importance of complementary data from the newly diagnosed cohort of KOMET-007, noting that these studies will help determine whether ziftomenib can become part of the frontline treatment paradigm.