Kura Oncology Reports Preclinical Data Supporting Opportunity for Ziftomenib in Treatment of Gastrointestinal Stromal Tumors (GIST)
Kura Oncology (KURA) reported promising preclinical data for its menin inhibitor ziftomenib in treating gastrointestinal stromal tumors (GIST). The combination of ziftomenib and imatinib demonstrated robust antitumor activity in both imatinib-sensitive and resistant GIST models. The data shows the combination works through a synthetic lethal mechanism, with ziftomenib targeting epigenetic vulnerabilities in GIST tumors. Following FDA clearance of the IND application in August 2024, Kura plans to initiate a proof-of-concept study combining ziftomenib with imatinib in advanced GIST patients after imatinib failure in 1H 2025.
Kura Oncology (KURA) ha riportato dati preclinici promettenti per il suo inibitore della menina ziftomenib nel trattamento dei tumori stromali gastrointestinali (GIST). La combinazione di ziftomenib e imatinib ha dimostrato una robusta attività antitumorale sia nei modelli di GIST sensibili che resistenti all'imatinib. I dati mostrano che la combinazione funziona attraverso un meccanismo letale sintetico, con ziftomenib che prende di mira le vulnerabilità epigenetiche nei tumori GIST. Dopo l'approvazione da parte della FDA dell'applicazione IND nell'agosto 2024, Kura intende avviare uno studio di proof-of-concept che combina ziftomenib con imatinib nei pazienti con GIST avanzato dopo il fallimento dell'imatinib nella prima metà del 2025.
Kura Oncology (KURA) reportó datos preclínicos prometedores para su inhibidor de menin ziftomenib en el tratamiento de tumores estromales gastrointestinales (GIST). La combinación de ziftomenib e imatinib demostró una fuerte actividad antitumoral tanto en modelos de GIST sensibles como resistentes a imatinib. Los datos muestran que la combinación funciona a través de un mecanismo letal sintético, con ziftomenib dirigiéndose a las vulnerabilidades epigenéticas en los tumores GIST. Tras la autorización de la FDA de la solicitud IND en agosto de 2024, Kura planea iniciar un estudio de prueba de concepto combinando ziftomenib con imatinib en pacientes con GIST avanzado tras el fracaso de imatinib en la primera mitad de 2025.
Kura Oncology (KURA)는 위장관 기질 종양(GIST) 치료를 위한 menin 억제제 ziftomenib의 유망한 전임상 데이터를 보고했습니다. ziftomenib과 imatinib의 조합은 imatinib에 민감한 GIST 모델과 저항성 GIST 모델 모두에서 강력한 항종양 활성을 나타냈습니다. 데이터는 이 조합이 합성 치사 메커니즘을 통해 작동하며, ziftomenib이 GIST 종양의 후천적 취약점을 표적한다는 것을 보여줍니다. 2024년 8월 FDA의 IND 신청 승인을 받은 후, Kura는 2025년 상반기 imatinib 실패 후 진행된 GIST 환자에서 ziftomenib과 imatinib을 결합한 개념 증명 연구를 시작할 계획입니다.
Kura Oncology (KURA) a rapporté des données précliniques prometteuses pour son inhibiteur de menin ziftomenib dans le traitement des tumeurs stromales gastro-intestinales (GIST). La combinaison de ziftomenib et d'imatinib a montré une forte activité antitumorale aussi bien dans des modèles de GIST sensibles qu résistants à l'imatinib. Les données montrent que la combinaison agit par un mécanisme létal synthétique, avec ziftomenib ciblant les vulnérabilités épigénétiques dans les tumeurs GIST. Suite à l'approbation de la demande IND par la FDA en août 2024, Kura prévoit de lancer une étude de preuve de concept combinant ziftomenib avec imatinib chez des patients atteints de GIST avancé après l'échec de l'imatinib au premier semestre 2025.
Kura Oncology (KURA) hat vielversprechende präklinische Daten zu seinem Menin-Hemmer ziftomenib bei der Behandlung von gastrointestinalen Stromatumoren (GIST) veröffentlicht. Die Kombination aus ziftomenib und imatinib zeigte eine starke antitumorale Aktivität sowohl in imatinib-sensitiven als auch in resistenten GIST-Modellen. Die Daten zeigen, dass die Kombination über einen synthetischen lethalen Mechanismus wirkt, wobei ziftomenib epigenetische Schwachstellen in GIST-Tumoren angreift. Nach der Genehmigung des IND-Antrags durch die FDA im August 2024 plant Kura, im ersten Halbjahr 2025 eine Machbarkeitsstudie zur Kombination von ziftomenib und imatinib bei fortgeschrittenen GIST-Patienten nach dem Versagen von imatinib zu starten.
- Preclinical data shows robust antitumor activity in both imatinib-sensitive and resistant GIST models
- FDA cleared IND application for ziftomenib in GIST treatment
- Potential for broader application across all GIST patients regardless of KIT mutation status
- Clinical trials in humans not yet started
- Proof-of-concept study delayed until 1H 2025
Insights
The preclinical data for ziftomenib in GIST treatment represents a significant breakthrough. The combination with imatinib shows robust synergistic effects in both imatinib-sensitive and resistant models, addressing a critical unmet need in GIST treatment resistance. The mechanism of action is particularly noteworthy - by targeting epigenetic vulnerabilities and reducing KIT expression, the combination effectively silences key cancer signaling pathways.
The data is compelling because it demonstrates efficacy regardless of KIT mutation status, suggesting broad applicability across GIST patients. The planned proof-of-concept study in 2025 could potentially establish a new treatment paradigm, especially considering imatinib's established safety profile and widespread availability as a generic drug. This could lead to faster regulatory pathway and market adoption if clinical trials prove successful.
– Combination of ziftomenib and imatinib shows robust and durable antitumor activity in imatinib-sensitive (1L) and imatinib-resistant (2L/3L) GIST models –
– Proof-of-concept study of ziftomenib plus imatinib in patients with advanced GIST after imatinib failure to begin in 1H 2025 –
SAN DIEGO, Oct. 24, 2024 (GLOBE NEWSWIRE) -- Kura Oncology, Inc. (Nasdaq: KURA), a clinical-stage biopharmaceutical company committed to realizing the promise of precision medicines for the treatment of cancer, today reported preclinical data supporting the development of the Company’s menin inhibitor, ziftomenib, for the treatment of advanced gastrointestinal stromal tumors (GIST).
The new findings are being presented at the 36th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics in Barcelona. A copy of the poster, entitled “Menin Inhibitor Ziftomenib Synergizes with Imatinib in Tyrosine Kinase Inhibitor (TKI)-Resistant Gastrointestinal Stromal Tumor Models,” is available in the Posters and Presentations section on Kura’s website.
“Kura has generated a substantial body of preclinical data that support potential for ziftomenib in combination with KIT inhibitors for the treatment of patients with advanced GIST,” said Francis Burrows, Ph.D., Senior Vice President, Translational Research. “Our results indicate that the combination of ziftomenib and imatinib acts via a synthetic lethal mechanism through which ziftomenib targets an epigenetic vulnerability of GIST tumors, creating potent synergy even with KIT inhibitors that are otherwise inactive as monotherapy. Indeed, the activity of ziftomenib appears to be agnostic to the mutational status of KIT in GIST, suggesting an opportunity to explore the combination for all patients, even in the frontline setting.”
The combination of ziftomenib and imatinib unexpectedly showed robust and durable antitumor activity in both imatinib-sensitive and imatinib-resistant GIST patient-derived xenograft models, and in all cases was significantly superior to imatinib monotherapy. Mechanistically, the data reveal a KIT-dependent mechanism, with ziftomenib and imatinib combining to sharply reduce KIT expression and/or activity, effectively silencing both the ERK and AKT/mTOR signaling pathways and driving robust cell cycle arrest and apoptosis.
Given that imatinib is well established as the frontline standard of care in patients with GIST, and that generic versions are available, imatinib represents a promising combination partner for ziftomenib.
In August 2024, Kura announced clearance by the U.S. Food and Drug Administration (FDA) of the Investigational New Drug (IND) application for ziftomenib for the treatment of advanced GIST. The Company is now preparing to initiate a proof-of-concept study evaluating ziftomenib and imatinib in patients with advanced GIST after imatinib failure in the first half of 2025. For more information regarding the study, please visit www.clinicaltrials.gov (identifier: NCT06026410).
About GIST
Gastrointestinal stromal tumors (GIST) are the most common form of sarcoma, characterized as KIT-dependent solid tumors. Despite the successful disease control achieved with imatinib in advanced GIST patients, most patients eventually progress due to acquired secondary KIT mutations. TKIs such as sunitinib can target imatinib-resistant genotypes and are approved in later lines, but response rates and long-term outcomes are modest, so new therapeutic options are needed. Previously published data show that the menin-MLL complex regulates KIT expression in GIST cells, and menin inhibitors display additive therapeutic activity in combination with imatinib in imatinib-sensitive GIST models1.
About Ziftomenib
Ziftomenib is a potent, 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 relapsed/refractory (R/R) NPM1-mutant acute myeloid leukemia (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, 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.
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 efficacy, safety and therapeutic potential of ziftomenib, potential benefits of combining ziftomenib with appropriate standards of care, and progress and expected timing of the ziftomenib program and 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 Securities and Exchange Commission (SEC), including the Company’s Form 10-Q for the quarter ended June 30, 2024 filed with the SEC on August 8, 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.
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
1 Hemming ML et al., Cancer Discov. 2022;12:1804-1823.
FAQ
What are the key findings of Kura Oncology's preclinical study for ziftomenib in GIST treatment?
When will Kura Oncology (KURA) begin clinical trials for ziftomenib in GIST patients?
What regulatory approval has ziftomenib received for GIST treatment?
