Kura Oncology and Kyowa Kirin have disclosed promising results from the phase 2 clinical trial of their oral leukemia drug, ziftomenib, as the U.S. Food and Drug Administration (FDA) reviews the selective menin inhibitor for potential approval. The study enrolled 92 heavily pretreated patients diagnosed with relapsed or refractory (R/R) acute myeloid leukemia (AML) harboring the NPM1 mutation.
Although the companies initially announced in February that the trial met its primary endpoint—demonstrating a statistically significant improvement in complete remission (CR) and partial hematologic recovery (CRh)—detailed data were withheld until the American Society of Clinical Oncology (ASCO) annual meeting in Chicago.
At ASCO, Kura and Kyowa revealed that 21 patients out of 92 achieved either full remission or remission with some blood cell recovery, resulting in a combined CR/CRh rate of 23%. This outcome aligns closely with earlier analyst predictions, such as those from TD Cowen, which anticipated a remission rate in the mid-20% range.
Specifically, 13 patients reached full complete remission (CR), while 8 patients attained partial hematological recovery (CRh). The median duration of these responses was reported as 3.7 months, with 12 patients demonstrating no detectable residual cancer cells. The median overall survival (OS) across all participants was six months, increasing substantially to 16.4 months for patients who responded to the treatment.
Following these encouraging results, Kura Oncology and Kyowa Kirin submitted a formal approval request to the FDA in April for ziftomenib's use in relapsed or refractory NPM1-mutant AML. Both companies also intend to initiate two phase 3 clinical trials later this year. These trials will focus on AML patients with either NPM1 or KMT2A gene mutations, including patients unable to undergo intensive chemotherapy.
Kura's Chief Medical Officer, Dr. Mollie Leoni, highlighted ziftomenib's consistent safety and tolerability, emphasizing the drug's low myelosuppression rate of 3%, minimal treatment discontinuations due to adverse events, no clinically significant QTc prolongation, absence of drug-drug interactions, and effective management of differentiation syndrome through protocol-specific measures.
Kyowa Kirin, based in Japan, invested $330 million in ziftomenib development last year and committed up to $1.1 billion in milestone payments. The two companies have agreed to jointly lead the launch of multiple trials for AML and other hematologic malignancies over the coming years. Kura will finance development of trials outside the U.S. through 2028, after which both biopharmaceutical firms will equally share ongoing costs.
[1]. https://dailynews.ascopubs.org/do/komet-001-demonstrates-efficacy-ziftomenib-patients-r-r-npm1--mutant-aml
