Kura Oncology and Kyowa Kirin Report Positive Combination Data for Ziftomenib at American Society of Hematology Annual Meeting
Rhea-AI Summary
Kura Oncology and Kyowa Kirin announced positive interim data from the Phase 1a portion of KOMET-007 trial, evaluating ziftomenib in combination with standard treatments for acute myeloid leukemia (AML). The study showed impressive results with a 100% complete remission rate in NPM1-m and 83% in KMT2A-r first-line adverse risk AML patients when combined with 7+3 therapy.
Key highlights include 100% survival rate in first-line NPM1-m and 96% in KMT2A-r AML patients, with median follow-up of 31 and 19 weeks respectively. The drug demonstrated promising activity in relapsed/refractory cases with venetoclax/azacitidine combination. Ziftomenib was well-tolerated across all dose levels, with manageable side effects.
Based on these positive results, the companies plan to initiate KOMET-017, a global Phase 3 study, in mid-2025.
Positive
- 100% complete remission rate in NPM1-m and 83% in KMT2A-r first-line AML patients
- High survival rates: 100% in NPM1-m and 96% in KMT2A-r AML patients
- 76% MRD negativity in NPM1-m and 75% in KMT2A-r patients
- 68% overall response rate in R/R NPM1-m population with ven/aza combination
Negative
- Lower response rates in previously venetoclax-exposed patients (50% ORR)
- Only 30% response rate in KMT2A-r patients with ven/aza combination
Insights
The interim analysis from KOMET-007 demonstrates exceptional efficacy with ziftomenib combinations. The 100% CR rate in NPM1-m and 83% CR rate in KMT2A-r first-line AML patients are remarkable outcomes in this difficult-to-treat population. The high MRD negativity rates (
The safety profile is particularly encouraging, with manageable differentiation syndrome rates of just
The relapsed/refractory data showing activity in venetoclax-experienced patients is clinically significant, as these patients typically have treatment options. The planned Phase 3 KOMET-017 study's dual-arm design targeting both intensive and non-intensive therapy pathways could position ziftomenib as a standard of care across the AML treatment spectrum.
This data release represents a significant value inflection point for Kura Oncology. The exceptional efficacy in first-line AML, particularly the 100% complete remission rate in NPM1-mutant patients, positions ziftomenib as a potential blockbuster therapy. The market opportunity is substantial, as NPM1 mutations occur in approximately
The partnership with Kyowa Kirin adds strategic value, bringing expertise in hematological malignancies and global commercialization capabilities. The planned Phase 3 KOMET-017 study in mid-2025 provides a clear regulatory pathway. The strong safety profile and compatibility with standard treatments could drive broad adoption if approved.
For a company with an
– Interim analysis from Phase 1a portion of KOMET-007 shows
–
– Promising clinical activity in R/R NPM1-m and KMT2A-r AML with ven/aza, including ven-experienced patients –
– Ziftomenib generally well tolerated in combination with standards of care at all dose levels studied –
– Kura Oncology to host virtual investor event today at 8:00 a.m. ET –
SAN DIEGO and TOKYO, Dec. 09, 2024 (GLOBE NEWSWIRE) -- Kura Oncology, Inc. (Nasdaq: KURA, “Kura”) and Kyowa Kirin Co., Ltd. (TSE: 4151, “Kyowa Kirin”) provided encouraging clinical data from KOMET-007, a Phase 1 dose-escalation trial of ziftomenib, a highly selective oral investigational menin inhibitor, in combination with standards of care, including cytarabine/daunorubicin (7+3) and venetoclax/azacitidine (ven/aza), in patients with NPM1-mutant (NPM1-m) and KMT2A-rearranged (KMT2A-r) acute myeloid leukemia (AML).
These data were presented at the 2024 American Society of Hematology (ASH) Annual Meeting. An oral presentation highlighting ziftomenib combined with 7+3 in newly diagnosed (1L) NPM1-m and KMT2A-r adverse riski AML, and a poster featuring ziftomenib in combination with ven/aza in relapsed/refractory (R/R) NPM1-m and KMT2A-r AML are available in the Posters and Presentations section on Kura’s website.
Ziftomenib was generally well tolerated in combination at all dose levels evaluated across all cohorts in the Phase 1a dose-escalation portion of the study. No dose-limiting toxicities, evidence of ziftomenib-associated QTc prolongation, drug-drug interactions or additive myelosuppression were observed. In the 7+3 combination cohorts, on-target differentiation syndrome (DS) occurred in
Among the response-evaluable patients enrolled in the 7+3 combination cohort for patients with 1L NPM1-m or KMT2A-r adverse riski AML,
A total of 54 patients were enrolled in the combination cohort with ven/aza in R/R NPM1-m or KMT2A-r AML. The NPM1-m population achieved an overall response rate (ORR) of
“The findings presented at ASH underscore the potential of ziftomenib in combination with standards of care as an early intervention in the frontline setting of AML and could offer a meaningful opportunity to improve patient outcomes,” said Amer Zeidan, MBBS, MHS, chief of the Division of Hematologic Malignancies, director of Hematology Early Therapeutics Research at Yale Cancer Center, and lead investigator of the KOMET-007 trial. “The high rates of complete remission and MRD negativity across the 7+3 cohorts are particularly encouraging. The rapid enrollment in the Phase 1a portion of this study underscores the urgency and enthusiasm for further evaluating this combination approach.”
Kura and Kyowa Kirin recently announced plans for KOMET-017, a global, pivotal Phase 3 study evaluating ziftomenib in combination with standards of care for adults with newly diagnosed KMT2A-r or NPM1-m AML. The trial includes two independently powered, randomized, double-blind, placebo-controlled studies: a non-intensive therapy arm testing ziftomenib with ven/aza, and an intensive therapy arm testing ziftomenib with 7+3. The positive results from KOMET-007 reported at ASH reinforce Kura’s and Kyowa Kirin’s commitment to evaluating ziftomenib for patients across the continuum of frontline treatment options. The KOMET-017 study is expected to initiate in mid-2025.
“Starting patients on therapy early is essential to improving outcomes in AML,” said Mollie Leoni, M.D., Executive Vice President, Clinical Development at Kura Oncology. “The updated KOMET-007 data underscore the combination potential of ziftomenib in the frontline setting, strengthening our confidence in its ability to provide a valuable treatment option for a significant portion of the AML population. Together, the KOMET-007 Phase 1b trial and the KOMET-017 pivotal Phase 3 study will allow us to further explore this approach and the potential to transform care if approved for AML patients worldwide.”
“More than half of AML patients with an NPM1 mutation will relapse with poor survival outcomesii, making it a significant area of unmet medical need in the frontline setting,” said Takeyoshi Yamashita, Ph.D., Senior Managing Executive Officer and Chief Medical Officer of Kyowa Kirin. “The data observed to date represent the potential of ziftomenib to help address the treatment gap and improve upon current standards of care. Leveraging our hemato-oncology expertise and commitment to patients, we are committed to rapidly advancing the clinical development of ziftomenib.”
Virtual Investor Event
Kura will host a webcast and conference call featuring Kura Oncology management and Key Opinion Leaders Amir T. Fathi, MD, Associate Professor of Medicine at Harvard Medical School and Director of the Leukemia Program at Massachusetts General Cancer Center, and Amer Zeidan, MBBS, MHS, interim chief of the Division of Hematologic Malignancies, Director of Hematology Early Therapeutics Research at Yale Cancer Center. The live call may be accessed by dialing (800) 715-9871 for domestic callers and (646) 307-1963 for international callers and entering the conference ID: 4326549. A live webcast will be available here and in the Investors section of Kura’s website, with an archived replay available shortly after the event.
About Ziftomenib
Ziftomenib is a selective and oral menin inhibitor currently in development for the treatment of genetically defined AML patients with high unmet need. In April 2024, ziftomenib received Breakthrough Therapy Designation (BTD) by the FDA for the treatment of R/R NPM1-mutant AML based on data from Kura’s ongoing KOMET-001 clinical trial. Additional information about clinical trials for ziftomenib can be found at kuraoncology.com/clinical-trials/#ziftomenib.
About Kura Oncology
Kura Oncology is a clinical-stage biopharmaceutical company committed to realizing the promise of precision medicines for the treatment of cancer. The Company’s pipeline consists of small molecule drug candidates that target cancer signaling pathways. Ziftomenib is being investigated as a once-daily, oral drug candidate targeting the menin-KMT2A protein-protein interaction, has received BTD for the treatment of R/R NPM1-mutant AML. Kura has completed enrollment in a Phase 2 registration-directed trial of ziftomenib in R/R NPM1-mutant AML (KOMET-001). The Company is also conducting a series of clinical trials to evaluate ziftomenib in combination with current standards of care in newly diagnosed and R/R NPM1-mutant and KMT2A-rearranged AML. Kura is evaluating KO-2806, a next-generation farnesyl transferase inhibitor (FTI), in a Phase 1 dose-escalation trial as a monotherapy and in combination with targeted therapies (FIT-001). Tipifarnib, a potent and selective FTI, is currently in a Phase 1/2 trial in combination with alpelisib for patients with PIK3CA-dependent head and neck squamous cell carcinoma (KURRENT-HN). For additional information, please visit Kura’s website at www.kuraoncology.com and follow us on X and LinkedIn.
About Kyowa Kirin
Kyowa Kirin aims to discover and deliver novel medicines and treatments with life-changing value. As a Japan-based Global Specialty Pharmaceutical Company, Kyowa Kirin has invested in drug discovery and biotechnology innovation for more than 70 years and is currently working to engineer the next generation of antibodies and cell and gene therapies with the potential to help patients with high unmet medical needs, such as bone & mineral, intractable hematological diseases/hemato-oncology and rare diseases. A shared commitment to Kyowa Kirin’s values, to sustainable growth, and to making people smile unites Kyowa Kirin across the globe. You can learn more about the business of Kyowa Kirin at www.kyowakirin.com.
Kura Forward-Looking Statements
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 pursuit of a broad ziftomenib development program including frontline indications and combinations with targeted therapies; the efficacy, safety and therapeutic potential of ziftomenib; potential benefits of combining ziftomenib with appropriate standards of care, including chemotherapies; and progress and expected timing of the ziftomenib program and clinical trials, including the timing of initiation of the pivotal Phase 3 frontline study. 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, the risk that the collaboration with Kyowa Kirin is unsuccessful, 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 Securities and Exchange Commission (SEC), including the Company’s Form 10-Q for the quarter ended September 30, 2024 filed with the SEC on November 7, 2024, which are available at www.sec.gov. Such forward-looking statements are current only as of the date they are made, and Kura assumes no obligation to update any forward-looking statements, whether as a result of new information, future events or otherwise.
Amer Zeidan has consulted and received honoraria from Kura. Opinions expressed are his own and do not necessarily represent those of his employer.
Kura Contacts
Investors:
Pete De Spain
Executive Vice President, Investor Relations &
Corporate Communications
(858) 500-8833
pete@kuraoncology.com
Media:
Cassidy McClain
Vice President
Inizio Evoke Comms
(619) 849-6009
cassidy.mcclain@inizioevoke.com
Kyowa Kirin Contacts
Wataru Suzuki
Corporate Communications Department – Global
media@kyowakirin.com
Lauren Walrath
Vice President, Public Affairs – North America
lauren.walrath.g4@kyowakirin.com
i Age ≥ 60 years and/or treatment-related AML and/or adverse risk cytogenetics per European LeukemiaNet (ELN)
ii Prata PH, Bally C, Prebet T, et al. NPM1 mutation is not associated with prolonged complete remission in acute myeloid leukemia patients treated with hypomethylating agents. Haematologica. 2018;103(10):e455-e457.
FAQ
What were the complete remission rates for ziftomenib in the KOMET-007 trial for KURA?
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What were the survival rates in the KOMET-007 trial for KURA's ziftomenib?
