Kura Oncology and Kyowa Kirin have shared details of the phase 2 win for their oral leukemia treatment ziftomenib as the FDA mulls whether to greenlight the selective menin inhibitor.
The trial of ziftomenib enrolled 92 heavily pretreated patients with relapsed or refractory (R/R) NPM1-mutant acute myeloid leukemia (AML). Kura and Kyowa announced back in February that the midstage study had hit its primary endpoint of demonstrating a statistically significant improvement in complete response (CR) rate as well as partial hematological recovery (CRh) but held back the data until today.
In a session at the American Society of Clinical Oncology (ASCO) annual meeting in Chicago, the companies revealed that 21 patients had either achieved full remission or a remission with some blood cell recovery, equivalent to a CR/CRh rate of 23%.
The trial was powered to detect a CR/CRh rate of 20% to 30%, and today’s data seem to fall just within the ballpark expectation of TD Cowen analysts, who predicted at the start of the year that the trial would generate a CR/CRh rate “in the mid-20%s.”
A total of 13 patients had a CR, and the remaining eight had a CRh, Kura and Kyowa explained in an accompanying June 2 release. The median duration of these responses was 3.7 months, with 12 of the patients free of any residual cancer cells.
A median OS rate of six months was seen across all patients in the study, rising to 16.4 months among those who responded to treatment.
The companies submitted an approval request to the FDA in April for ziftomenib in R/R NPM1-mutant AML and have plans to launch two phase 3 trials later this year in AML patients with NPM1 or KMT2A gene mutations and in NPM1 patients who cannot receive intensive chemotherapy.
“Beyond ziftomenib’s clinical activity, we are highly encouraged by its consistent safety and tolerability profile,” Kura Chief Medical Officer Mollie Leoni, M.D., said in the release.
“Notably, the low rate of myelosuppression, 3% discontinuation rate due to ziftomenib [treatment-related adverse events], lack of clinically significant QTc prolongation, absence of drug-drug interactions and effective management of differentiation syndrome through protocol-specified mitigation strategies underscore ziftomenib’s favorable benefit-risk profile for patients with relapsed or refractory NPM1-mutated AML,” Leoni added.
Japan-based Kyowa fronted $330 million last year and pledged up to $1.1 billion in milestones to get in on the ziftomenib action. The two companies are sharing responsibility for launching various trials in AML and other blood cancers “over the next several years,” with Kura funding the development of ex-U.S. trials until the end of 2028, after which point the biopharmas will split the costs.