Key Data on Ziftomenib in Relapsed/Refractory AML and Mutant Subgroups


Harry P. Erba, MD, PhD, highlights key data on ziftomenib in patients with relapsed/refractory acute myeloid leukemia and its potential as part of a combination regimen.

The phase1/2 KOMET-001 trial (NCT04067336), which analyzed ziftomenib in patients with relapsed/refractory acute myeloid leukemia (AML), identified notable antileukemic activity, with particular benefit in patients with NPM1-mutant disease, according to Harry P. Erba, MD, PhD, a hematologic oncologist at Duke Health.

During the 2022 American Society of Hematology (ASH) Annual Meeting, CancerNetwork® spoke with Erba about the significance of the findings in the overall population and in key patient subgroups.

A 600 mg dose of the agent resulted in a complete response rate of 30.0% in the NPM1-mutated group, 2 of whom had concurrent IDH1/2 mutations and 2 had IDH1/2 and FLT3-ITD/TKD mutations.There was also an overall response rate of 57% in patients with IDH1/2 co-mutations (n = 7).


We know these patients are relapsing. A testimony to that is that we were able to find and put 20 patients on study with NPM1-mutated disease in the relapsed/refractory setting on the 600 mg recommended phase 2 dose. What we’re excited about is [the possibility of] single-agent activity for NPM1-mutated disease that may be very useful to some of our older patients who get HMA [hypomethylating agents], relapse, and don’t have any other options. A single-agent menin-KMT2A inhibitor with a 30% to 40% response rate with a tolerable toxicity profile would definitely be an advantage.

Clearly, [where we intend to move is] where we go with all of these targeted therapies: in combination with chemotherapy, other targeted therapies, and maybe even immunotherapy at some point. [Currently, there is a] phase 2 study that has ziftomenib in combination with intensive chemotherapy, HMA plus venetoclax [Venclexta], and—in FLT3-mutated patients—gilteritinib [Xospata] in the relapsed/refractory setting. Arms of the study of are looking at HMA/venetoclax or intensive chemotherapy with ziftomenib in previously untreated patients in the appropriate patient population—either fit or unfit for intensive chemotherapy.


Erba HP, Fathi AT, Issa GC, et al. Update on a phase 1/2 first-in-human study of the menin-KMT2A (MLL) inhibitor ziftomenib (KO-539) in patients with relapsed or refractory acute myeloid leukemia. Blood. 2022; 140(suppl 1):153-156. doi:10.1182/blood-2022-167412

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