Kura Oncology Announces First Patients Dosed in Phase 1 Combination Trial of Ziftomenib for the Treatment of Advanced GIST
Kura Oncology (KURA) has initiated dosing in KOMET-015, a Phase 1 clinical trial evaluating ziftomenib in combination with imatinib for patients with advanced gastrointestinal stromal tumors (GIST) who failed imatinib treatment. The trial aims to assess safety, tolerability, and preliminary antitumor activity.
Preclinical studies showed the combination demonstrates robust antitumor activity in both imatinib-sensitive and resistant GIST models through a synthetic lethal mechanism. With 4,000-6,000 new GIST cases diagnosed annually in the U.S. and 60% of patients developing imatinib resistance within two years, ziftomenib could potentially delay or overcome this resistance.
The KOMET-015 Phase 1a/1b trial will evaluate safety, determine recommended Phase 2 dosing, and measure endpoints including clinical benefit, overall response rate, progression-free survival, and overall survival. This marks the first clinical trial combining a menin inhibitor with standard GIST treatments.
Kura Oncology (KURA) ha iniziato la somministrazione nel trial clinico di Fase 1 KOMET-015, che valuta ziftomenib in combinazione con imatinib per pazienti con tumori stromali gastrointestinali (GIST) avanzati, resistenti al trattamento con imatinib. Lo studio mira a valutare la sicurezza, la tollerabilità e l'attività antitumorale preliminare.
Studi preclinici hanno dimostrato che la combinazione mostra un’attività antitumorale significativa sia nei modelli di GIST sensibili che resistenti a imatinib, attraverso un meccanismo letale sintetico. Con 4.000-6.000 nuovi casi di GIST diagnosticati ogni anno negli Stati Uniti e il 60% dei pazienti che sviluppa resistenza a imatinib entro due anni, ziftomenib potrebbe ritardare o superare questa resistenza.
Il trial KOMET-015 di Fase 1a/1b valuterà la sicurezza, definirà la dose raccomandata per la Fase 2 e misurerà endpoint come beneficio clinico, tasso di risposta globale, sopravvivenza libera da progressione e sopravvivenza complessiva. Questo è il primo studio clinico che combina un inibitore di menina con i trattamenti standard per il GIST.
Kura Oncology (KURA) ha iniciado la dosificación en KOMET-015, un ensayo clínico de Fase 1 que evalúa ziftomenib en combinación con imatinib para pacientes con tumores estromales gastrointestinales (GIST) avanzados que no respondieron al tratamiento con imatinib. El estudio busca evaluar la seguridad, tolerabilidad y la actividad antitumoral preliminar.
Los estudios preclínicos mostraron que la combinación presenta una fuerte actividad antitumoral tanto en modelos de GIST sensibles como resistentes a imatinib, mediante un mecanismo letal sintético. Con 4,000-6,000 nuevos casos de GIST diagnosticados anualmente en EE. UU. y el 60% de los pacientes desarrollando resistencia a imatinib en dos años, ziftomenib podría retrasar o superar esta resistencia.
El ensayo KOMET-015 de Fase 1a/1b evaluará la seguridad, determinará la dosis recomendada para la Fase 2 y medirá puntos finales como beneficio clínico, tasa de respuesta global, supervivencia libre de progresión y supervivencia global. Este es el primer ensayo clínico que combina un inhibidor de menina con los tratamientos estándar para GIST.
Kura Oncology (KURA)는 진행성 위장관 기질 종양(GIST) 환자 중 이마티닙 치료에 실패한 환자를 대상으로 이마티닙과 지프토메닙 병용 투여를 평가하는 1상 임상시험 KOMET-015의 투약을 시작했습니다. 이 임상시험은 안전성, 내약성 및 초기 항종양 효과를 평가하는 것을 목표로 합니다.
전임상 연구에서 이 병용 요법은 이마티닙에 민감한 모델과 내성 모델 모두에서 합성 치사 메커니즘을 통해 강력한 항종양 활성을 보였습니다. 미국에서 매년 4,000~6,000건의 신규 GIST가 진단되고 환자의 60%가 2년 내에 이마티닙 내성을 개발하는 상황에서, 지프토메닙은 이러한 내성을 지연시키거나 극복할 가능성이 있습니다.
KOMET-015 1a/1b상 시험은 안전성을 평가하고 2상 권장 용량을 결정하며, 임상적 이점, 전체 반응률, 무진행 생존기간 및 전체 생존율 등의 평가 지표를 측정할 예정입니다. 이는 메닌 억제제를 표준 GIST 치료와 병용하는 최초의 임상시험입니다.
Kura Oncology (KURA) a débuté la phase de dosage dans KOMET-015, un essai clinique de phase 1 évaluant ziftoménib en association avec l’imatinib chez des patients atteints de tumeurs stromales gastro-intestinales (GIST) avancées, résistantes à l’imatinib. L’essai vise à évaluer la sécurité, la tolérance et l’activité antitumorale préliminaire.
Des études précliniques ont montré que la combinaison présente une forte activité antitumorale dans des modèles de GIST sensibles et résistants à l’imatinib, via un mécanisme létal synthétique. Avec 4 000 à 6 000 nouveaux cas de GIST diagnostiqués chaque année aux États-Unis et 60 % des patients développant une résistance à l’imatinib en deux ans, le ziftoménib pourrait retarder ou surmonter cette résistance.
L’essai KOMET-015 de phase 1a/1b évaluera la sécurité, déterminera la dose recommandée pour la phase 2 et mesurera des critères d’évaluation tels que le bénéfice clinique, le taux de réponse globale, la survie sans progression et la survie globale. Il s’agit du premier essai clinique combinant un inhibiteur de la ménine aux traitements standards du GIST.
Kura Oncology (KURA) hat mit der Dosierung in KOMET-015 begonnen, einer Phase-1-Studie, die Ziftomenib in Kombination mit Imatinib bei Patienten mit fortgeschrittenen gastrointestinalen Stromatumoren (GIST) untersucht, die auf Imatinib nicht angesprochen haben. Die Studie zielt darauf ab, Sicherheit, Verträglichkeit und vorläufige antitumorale Aktivität zu bewerten.
Präklinische Studien zeigten, dass die Kombination eine starke antitumorale Wirkung sowohl in Imatinib-empfindlichen als auch resistenten GIST-Modellen durch einen synthetisch letalen Mechanismus zeigt. Mit 4.000-6.000 neuen GIST-Fällen pro Jahr in den USA und 60 % der Patienten, die innerhalb von zwei Jahren eine Imatinib-Resistenz entwickeln, könnte Ziftomenib diese Resistenz verzögern oder überwinden.
Die KOMET-015 Phase 1a/1b-Studie wird die Sicherheit bewerten, die empfohlene Dosis für Phase 2 bestimmen und Endpunkte wie klinischen Nutzen, Gesamtansprechrate, progressionsfreies Überleben und Gesamtüberleben messen. Dies ist die erste klinische Studie, die einen Menin-Inhibitor mit Standardtherapien für GIST kombiniert.
- First-in-class menin inhibitor combination trial for GIST treatment
- Promising preclinical data showing efficacy in both imatinib-sensitive and resistant cases
- Addresses large market with 4,000-6,000 new GIST cases annually in U.S.
- Potential solution for 60% of patients who develop imatinib resistance
- Early Phase 1 stage with no proven clinical efficacy yet
- Will require extensive testing and time before potential market approval
- Faces competition from existing GIST treatments
Insights
Kura's expansion of ziftomenib into GIST represents scientific innovation by targeting resistance mechanisms with a novel approach, addressing significant unmet need.
Kura Oncology's initiation of the KOMET-015 trial marks a scientifically significant expansion of menin inhibition beyond blood cancers into solid tumors. Gastrointestinal stromal tumors (GIST) affect 4,000-6,000 new patients annually in the U.S., and while imatinib revolutionized frontline treatment, the 60% resistance rate within two years creates a substantial clinical challenge.
The mechanism of action here deserves attention. Ziftomenib works through menin inhibition, fundamentally different from traditional tyrosine kinase inhibitors used in GIST. The described "synthetic lethal mechanism" suggests ziftomenib targets vulnerabilities specifically induced by TKI treatment, potentially creating a complementary rather than competitive therapeutic strategy. This epigenetic approach to overcome imatinib resistance represents a novel paradigm in GIST treatment.
The preclinical data showing activity in both imatinib-sensitive and imatinib-resistant models suggests potential application across multiple treatment lines. The endorsements from sarcoma specialists at premier cancer centers (Memorial Sloan Kettering and MD Anderson) lend credibility to this approach. However, as with all Phase 1 trials, the primary focus remains establishing safety parameters and determining optimal dosing before efficacy can be thoroughly evaluated.
Kura expands ziftomenib beyond AML into solid tumors, addressing GIST's unmet need with novel mechanism, though years from potential commercialization.
Kura's strategic expansion of ziftomenib into GIST represents important pipeline diversification. This broadens the potential applications of their lead menin inhibitor beyond the previously established NPM1-mutant and KMT2A-rearranged AML indications. For investors, this represents a potential de-risking strategy by not concentrating all resources into a single indication.
The GIST market, while smaller than AML with 4,000-6,000 new U.S. cases annually, faces options after imatinib failure. By targeting the significant 60% of patients who develop resistance within two years, Kura is addressing a clear unmet medical need with market potential. The novel combination approach could position ziftomenib as a companion to standard therapy rather than competing directly with established treatments.
This Phase 1a/1b trial follows standard development pathways, starting with dose-escalation before moving to expansion cohorts. The design includes key efficacy endpoints such as overall response rate, progression-free survival, and overall survival. Being the first menin inhibitor evaluated in GIST gives Kura potential first-mover advantage with this mechanism, although the GIST treatment landscape remains competitive.
The trial initiation represents meaningful pipeline expansion and clinical progress, though investors should recognize this program remains in early development with several years of clinical studies required before potential regulatory submission.
– Phase 1 dose-escalation study to evaluate ziftomenib in combination with imatinib in patients with advanced GIST after imatinib failure –
– Combination of ziftomenib and imatinib shows robust and durable antitumor activity in imatinib-sensitive and imatinib-resistant GIST preclinical models –
SAN DIEGO, April 28, 2025 (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 announced that the first patients have been dosed in KOMET-015, a Phase 1 clinical trial of ziftomenib, the Company’s potent and selective, oral investigational menin inhibitor, in patients with advanced gastrointestinal stromal tumors (GIST) after imatinib failure.
“Building on compelling clinical activity of ziftomenib in patients with NPM1-mutant and KMT2A-rearranged AML, we are committed to evaluating the full therapeutic potential of menin inhibitors for the treatment of cancer,” said Mollie Leoni, M.D., Chief Medical Officer of Kura Oncology. “Approximately 4,000 to 6,000 new cases of GIST are diagnosed each year in the U.S., and advanced GIST patients have limited treatment options. Our preclinical data demonstrate the combination of ziftomenib and imatinib provides robust and durable antitumor activity in both imatinib-sensitive (1L) and imatinib-resistant (2L/3L) GIST patient-derived xenograft models, and we look forward to seeing whether the combination offers potential to transform the treatment paradigm.”
In preclinical studies, the data demonstrates the combination exerts antitumor activity via a synthetic lethal mechanism through which ziftomenib epigenetically targets a vulnerability of GIST tumors actively induced by even ineffective tyrosine kinase inhibitor (TKI) treatments. Sixty percent of patients develop resistance to imatinib, the frontline standard of care for GIST, within two years, and ziftomenib has the potential to delay the onset of or overcome that resistance in these patients.
“This study is an important step in developing new combination treatments to potentially improve outcomes for patients with advanced gastrointestinal stromal tumors, a disease indication for which new therapeutic options are needed,” said Mrinal Gounder, M.D., Sarcoma Oncologist & Early Phase Drug Development Specialist at Memorial Sloan Kettering Cancer Center. “KOMET-015 builds upon the promising preclinical data observed with ziftomenib in combination with imatinib in GIST models and we look forward to evaluating the investigational drug candidate and its potential to transform the treatment landscape.”
“Until now, most approaches to treating gastrointestinal stromal tumors rely on targeted KIT inhibition via tyrosine kinase inhibitors such as imatinib, however most patients eventually progress due to acquired secondary KIT mutations highlighting the need for new treatment options,” said Shreyaskumar Patel, M.D., Center Medical Director, Sarcoma Center, at The University of Texas MD Anderson Cancer Center. “We are highly encouraged by the substantial preclinical data generated to date supporting the combination for ziftomenib in combination with KIT inhibitors in advanced GIST, and the dosing of the first patients marks an important milestone to address the meaningful unmet need for these patients.”
The KOMET-015 Phase 1a/1b, open-label, dose-escalation trial is designed to evaluate the safety, tolerability, and preliminary antitumor activity of ziftomenib in combination with imatinib in adults with GIST who have documented disease progression while currently on or previously treated with imatinib. Upon completion of the dose-escalation portion of the trial, expansion cohorts are planned to further assess the safety, tolerability, and clinical activity of ziftomenib. The primary objectives include evaluation of safety and tolerability and determination of the recommended Phase 2 dose, and key secondary endpoints include clinical benefit, overall response rate (ORR), progression free survival (PFS), duration of response, and overall survival (OS).
Currently, there are no other clinical trials evaluating the combination of a menin inhibitor with standards of care for the treatment of GIST. For more information regarding the KOMET-015 trial, please visit www.clinicaltrials.gov (identifier: NCT06655246).
About GIST
Gastrointestinal stromal tumors (GIST) are the most common form of sarcoma, and are characterized as KIT-dependent solid tumors, with an estimated 4,000 to 6,000 new cases diagnosed in the U.S. each year. 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 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.
About Ziftomenib
Ziftomenib is a once daily, oral investigational menin inhibitor currently in development for the treatment of genetically defined AML and GIST patients with high unmet need. In April 2024, ziftomenib received Breakthrough Therapy Designation (BTD) from the FDA for the treatment of relapsed/refractory (R/R) NPM1-mutant (NPM1-m) AML based on data from Kura’s KOMET-001 clinical trial. Additional information about clinical trials for ziftomenib can be found at www.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, designed to target cancer signaling pathways. Ziftomenib, a once-daily, oral menin inhibitor, is the first and only investigational therapy to receive BTD from the FDA for the treatment of R/R NPM1-m AML. In November 2024, Kura entered into a global strategic collaboration agreement with Kyowa Kirin Co., Ltd. to develop and commercialize ziftomenib for AML and other hematologic malignancies. Enrollment in a Phase 2 registration-directed trial of ziftomenib in R/R NPM1-m AML has been completed, and in the second quarter of 2025, the companies announced submission of a New Drug Application for ziftomenib for the treatment of adult patients with R/R NPM1-m AML. Kura and Kyowa Kirin are conducting a series of clinical trials to evaluate ziftomenib in combination with current standards of care in newly diagnosed and R/R NPM1-m and KMT2A-rearranged AML. Kura has also initiated a Phase 1 trial (KOMET-015) of ziftomenib in combination with imatinib in advanced GIST. KO-2806, a next-generation farnesyl transferase inhibitor (FTI), is being evaluated in a Phase 1 dose-escalation trial (FIT-001) as a monotherapy and in combination with targeted therapies for patients with various solid tumors. Tipifarnib, a potent and selective FTI, is currently in a Phase 1/2 trial (KURRENT-HN) in combination with alpelisib for patients with PIK3CA-dependent head and neck squamous cell carcinoma. For additional information, please visit Kura’s website at https://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 Kura’s product candidates, ziftomenib, tipifarnib and KO-2806; plans, trial designs and expected timing of clinical trials; the anticipated timing of submission of an NDA for ziftomenib; and the potential for menin inhibitors to shift the treatment paradigm for GIST. 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, 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.
Dr. Gounder has financial interests related to Kura Oncology.
Contacts
Investors:
Patti Bank
Managing Director
(415) 513-1284
patti.bank@icrhealthcare.com
Media:
Alexandra Weingarten
Associate Director, Corporate Communications
(858) 500-8822
alexandra@kuraoncology.com
FAQ
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