33% Response Rate in R/R AML with Single-Agent Therapy

Updated results from the phase 1b/2 KOMET-001 trial (NCT04067336) shared at the Society of Hematological Oncology 2025 Annual Meeting demonstrated that single-agent ziftomenib achieved an overall response rate of 33%, with a complete remission and complete remission with partial hematologic recovery rate of 25% in patients with relapsed/refractory NPM1-mutantacute myeloid leukemia (AML).1

Ghayas C. Issa, MD, MS, the presenting study author and an associate professor in the Department of Leukemia and in the Department of Genomic Medicine in the Division of Cancer Medicine at the University of Texas MD Anderson Cancer Center, spoke with CancerNetwork® about the implications of these results.

Foremost, he noted that the developer has submitted a package to the FDA, seeking approval for single agent ziftomenib in this indication.2 The agent is now being tested in frontline settings, as well as in combination with other therapies such as chemotherapy.

The phase 1 KOMET-007 (NCT05735184) and KOMET-008 (NCT06001788) trials were 2 examples of trials evaluating ziftomenib in combinations for the treatment of NPM1-mutant relapsed/refractory AML that he mentioned.

CancerNetwork: What are the potential clinical implications of these results?

Issa: Based on these results, there was a submission to the FDA for approval of ziftomenib for this indication, which is NPM1-mutant relapsed/refractory [AML]. We hope that, soon, this drug will be available as a standard of care for patients. Even more importantly, we’re trying to test it to improve outcomes for all patients, including newly diagnosed patients with NPM1. There are ongoing studies that will test the addition of ziftomenib to standard induction chemotherapy, either high-intensity chemotherapy, such as “7 + 3”, or in older, unfit patients, which is azacitidine and venetoclax. In the future, we hope that the addition of ziftomenib would improve the chances of a cure for patients by adding them to these therapies.

What other research is currently building off these results?

This is the randomized control study that is meant to be registrational, meaning if we meet the primary end point, this would be the new standard of care for induction treatment of NPM1-mutant [AML]. There are multiple other combination studies going on in the relapsed/refractory setting, such as combinations with [hypomethylating agents] and venetoclax—the KOMET-007 study—combinations with low-dose cytarabine, combinations with gilteritinib [Xospata], or combinations with high-intensity chemotherapy in the KOMET-008 study. All these [studies] are ongoing, and we’ll be presenting results soon.