Kura Oncology Presents Late-Breaking Clinical Data for Menin Inhibitor Ziftomenib at 2023 European Hematology Association (EHA) Congress
– 35% CR rate (7/20) among patients with relapsed/refractory NPM1-mutant AML treated at 600 mg dose (RP2D) –
– 33% (2/6) of patients with FLT3 co-mutations and 50% (4/8) of patients with IDH co-mutations achieved a CR on ziftomenib –
– Ziftomenib monotherapy drives durable remissions, with median DoR of 8.2 months –
– Data suggest ziftomenib is less likely to induce menin resistance mutations –
– Enrollment in Phase 2 registration-directed trial in NPM1-mutant AML continues to outperform projections –
– First combination study in NPM1-mutant and KMT2A-rearranged AML on track to dose first patients this quarter –
– Management to host virtual investor event at
The updated clinical data are being featured during a late-breaking oral session today at the 2023
“Our goal with our ziftomenib program is to transform the standard of care for patients with acute leukemias,” said
As of the data cutoff on
The median duration of response for all NPM1-mutant patients was 8.2 months (95% CI: 1.0 to NE), with a median follow-up of 8.8 months. The median duration of response for patients censored at SCT was 5.6 months (95% CI: 1.0 to NE). As of the cutoff date, three patients treated at 600 mg remain on study and in CR; an additional NPM1-mutant patient treated at 200 mg remained on ziftomenib for 36 cycles.
As part of an ongoing analysis, the resistance mutation MEN1-M3271 has been detected in three patients treated with ziftomenib: in two patients, the mutation was detected at study entry after the patients had progressed on a prior menin inhibitor, and in the third patient, the mutation was detected after four cycles of ziftomenib therapy and, despite the mutation, the patient was maintained in a condition of stable disease through cycle 7. These data show that MEN1 mutations developed in just 3% (1/29) of patients analyzed following treatment with ziftomenib and suggest that resistance mutations are less likely to evolve after prolonged exposure to ziftomenib monotherapy. A key new biochemical finding, confirmed by crystal structure, demonstrates that ziftomenib retains full activity against the MEN1-T349M mutation, detected in two-thirds of patients who acquired menin resistance mutations on another recent menin inhibitor trial.
“NPM1-mutant AML accounts for approximately 30% of AML cases annually and represents a disease of significant unmet need for which no approved targeted therapy exists,” said
Continuous daily dosing of ziftomenib was well tolerated and the safety profile remains consistent with features of underlying disease. The on-target effect of differentiation syndrome was manageable, with 15% of patients experiencing Grade 1 or 2 events and 5% experiencing a Grade 3 event.
Enrollment in a Phase 2 registration-directed study of ziftomenib in patients with relapsed/refractory NPM1-mutant AML continues to outperform projections. The study is expected to enroll a total of 85 patients at 62 U.S. and European sites. Kura is also preparing to initiate a series of studies to evaluate ziftomenib in combination with current standards of care in earlier lines of therapy and across multiple patient populations, including NPM1-mutant and KMT2A-rearranged AML. The Company has begun site activation in the first of these studies, KOMET-007, and is on track to dose the first patients this quarter.
Virtual Investor Event
Management will host a virtual investor event featuring company management and investigators from the Phase 1 trial of ziftomenib at
About Acute Myeloid Leukemia
AML is the most common acute leukemia in adults and begins when the bone marrow makes abnormal myeloblasts (white blood cells), red blood cells or platelets. Despite the many available treatments for AML, prognosis for patients remains poor. NPM1-mutations are among the most common genetic alterations, representing approximately 30% of AML cases. While patients with NPM1-mutant AML have high response rates to frontline therapy, relapse rates are high and survival outcomes are poor, with only 30% overall survival at 12 months in the relapsed or refractory setting. Additionally, NPM1 mutations frequently occur with co-mutations in other disease-associated genes, including FLT3, DNMT3A and IDH1/2, with prognosis heavily influenced by the occurrence of co-occurring mutations. Median overall survival is only approximately six months following relapse for NPM1-mutant patients. KMT2A-rearrangements are less frequent, representing approximately 5-10% of AML. No FDA-approved therapies targeting NPM1-mutant and KMT2A-rearranged AML currently exist.
Ziftomenib is a novel, once-daily, oral investigational drug candidate targeting the menin-KMT2A/MLL protein-protein interaction for treatment of genetically defined AML patients with high unmet need. In preclinical models, ziftomenib inhibits the KMT2A/MLL protein complex and exhibits downstream effects on HOXA9/MEIS1 expression and potent anti-leukemic activity in genetically defined preclinical models of AML. Ziftomenib has received Orphan Drug Designation from the
This news release contains certain forward-looking statements that involve risks and uncertainties that could cause actual results to be materially different from historical results or from any future results expressed or implied by such forward-looking statements. Such forward-looking statements include statements regarding, among other things, the efficacy, safety and therapeutic potential of ziftomenib, potential benefits of combining ziftomenib with appropriate standards of care, progress and expected timing of the ziftomenib program, and plans regarding future clinical trials. Factors that may cause actual results to differ materially include the risk that compounds that appeared promising in early research or clinical trials do not demonstrate safety and/or efficacy in later preclinical studies or clinical trials, the risk that Kura may not obtain approval to market its product candidates, uncertainties associated with performing clinical trials, regulatory filings, applications and other interactions with regulatory bodies, risks associated with reliance on third parties to successfully conduct clinical trials, the risks associated with reliance on outside financing to meet capital requirements, and other risks associated with the process of discovering, developing and commercializing drugs that are safe and effective for use as human therapeutics, and in the endeavor of building a business around such drugs. You are urged to consider statements that include the words “may,” “will,” “would,” “could,” “should,” “believes,” “estimates,” “projects,” “promise,” “potential,” “expects,” “plans,” “anticipates,” “intends,” “continues,” “designed,” “goal,” or the negative of those words or other comparable words to be uncertain and forward-looking. For a further list and description of the risks and uncertainties the Company faces, please refer to the Company's periodic and other filings with the
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Source: Kura Oncology, Inc.