Studies to Assess Ziftomenib in Combination With Ven+Aza or 7+3 in Patients With Untreated NPM1-m or KMT2A-r AML

Recruitment Status
RECRUITING
(See Contacts and Locations)Verified July 2026 by Kura Oncology, Inc.
Sponsor
Kura Oncology, Inc.
Information Provided by (Responsible Party)
Kura Oncology, Inc.
Clinicaltrials.gov Identifier
NCT07007312
Other Study ID Numbers:
KO-MEN-017
First Submitted
May 15, 2025
First Posted
June 4, 2025
Last Update Posted
August 19, 2026
Last Verified
July 2026

ClinicalTrials.gov processed this data on August 2026. Link to the current ClinicalTrials.gov record .

History of Changes

Study Details

Study Description

This protocol encompasses two phase 3, randomized, double-blind, placebo-controlled clinical studies to assess the efficacy, safety, and tolerability of ziftomenib in combination with: (a) the standard of care (SOC) nonintensive regimen (venetoclax \[ven\]+azacitidine \[aza\]) in untreated adults with nucleophosmin 1 mutated (NPM1-m) acute myeloid leukemia (AML); or (b) the SOC intensive regimen (cytarabine+daunorubicin induction, referred to here as 7+3, and cytarabine consolidation) in untreated adults with NPM1-m or lysine\[K\]-specific methyltransferase 2A rearranged (KMT2A-r) AML, as well as a maintenance phase.

Nonintensive Therapy Study (Ven+Aza)

Eligible NPM1-m patients will be enrolled and randomized to receive:

* Arm A: Ziftomenib in combination with ven+aza or

* Arm B: Placebo in combination with ven+aza.

Patients will be randomized to treatment arms in a double-blind manner.

Intensive Therapy Study (Cytarabine+Daunorubicin)

Eligible NPM1-m or KMT2A-r patients will be enrolled and randomized to 1 of the following treatment arms:

* Arm A: Ziftomenib+7+3 (induction), ziftomenib+cytarabine (consolidation), ziftomenib (maintenance) or

* Arm B: Ziftomenib+7+3 (induction), ziftomenib+cytarabine (consolidation), placebo (maintenance) or

* Arm C: Placebo+7+3 (induction), placebo+cytarabine (consolidation), placebo (maintenance).

Patients will be randomized to treatment arms in a double-blind manner.

Condition or DiseaseIntervention/Treatment
Acute Myeloid Leukemia (AML)
Drug: ZiftomenibDrug: PlaceboDrug: ZiftomenibDrug: ZiftomenibDrug: Placebo

Study Design

Study TypeInterventional
Actual Enrollment1300 participants
Design AllocationRandomized
Interventional ModelParallel Assignment
MaskingQuadruple
Primary PurposeTreatment
Official TitlePhase 3 Randomized, Double-blind, Placebo-controlled Studies Assessing Ziftomenib in Combination With Either Standard of Care Nonintensive (Venetoclax+Azacitidine) or Intensive (7+3) Therapy in Patients With Untreated NPM1 Mutated or KMT2A Rearranged Acute Myeloid Leukemia
Study Start DateSeptember 25, 2025
Actual Primary Completion Date5yrs 1mo from now
Actual Study Completion Date5yrs 1mo from now

Groups and Cohorts

Group/CohortIntervention/Treatment
Nonintensive Therapy Study, Arm A
Ziftomenib in combination with venetoclax+azacitidine
Drug: Ziftomenib
Oral administration
Nonintensive Therapy Study, Arm B
Placebo in combination with venetoclax+azacitidine
Drug: Placebo
Oral administration
Intensive Therapy Study, Arm A
Ziftomenib+cytarabine+daunorubicin (induction), ziftomenib+cytarabine (consolidation), ziftomenib (maintenance)
Drug: Ziftomenib
Oral administration
Intensive Therapy Study, Arm B
Ziftomenib+cytarabine+daunorubicin (induction), ziftomenib+cytarabine (consolidation), placebo (maintenance)
Drug: Ziftomenib
Oral administration
Intensive Therapy Study, Arm C
Placebo+cytarabine+daunorubicin (induction), placebo+cytarabine (consolidation), placebo (maintenance)
Drug: Placebo
Oral administration

Outcome Measures

Primary Outcome Measures
  1. Nonintensive Therapy Study: (Primary Endpoint for all countries): Overall survival (OS)
    OS
  2. Nonintensive Therapy Study: (Dual Primary Endpoint for US & US reference countries only): Complete remission (CR)
    CR rate per European Leukemia Network (ELN) 2022 criteria per Investigator assessment
  3. Intensive Therapy Study: (Primary Endpoint for all countries): Event-free survival (EFS)
    EFS
  4. Intensive Therapy Study: (Dual Primary Endpoint for US & US reference countries only): Complete remission (CR) with bone marrow (BM) measurable residual disease (MRD) negativity in NPM1-m patients
    CR rate per ELN 2022 criteria per Investigator assessment with central BM MRD negativity
Secondary Outcome Measures
  1. Nonintensive Therapy Study: (EU & EU reference countries only): Complete remission (CR)
    CR rate per ELN 2022 criteria per Investigator assessment
  2. Nonintensive Therapy Study: Bone marrow (BM) measurable residual disease (MRD) negativity
    Central BM MRD negativity rate
  3. Nonintensive Therapy Study: Complete remission (CR) + complete remission with partial hematologic recovery (CRh)
    CR + CRh rate per ELN 2022 criteria per Investigator assessment
  4. Nonintensive Therapy Study: Descriptive statistics of Adverse Events (AEs)
    Assessed by NCI-CTCAE v5.0
  5. Nonintensive Therapy Study: Area under the concentration-time curve (AUC) of ziftomenib and venetoclax
    To characterize the AUC of ziftomenib and venetoclax
  6. Nonintensive Therapy Study: Trough concentration (Ctrough) of ziftomenib and venetoclax
    To characterize the Ctrough of ziftomenib and venetoclax
  7. Nonintensive Therapy Study: Health-related patient-reported outcomes (PRO) assessments
    Health-related quality of life (HRQoL) was evaluated by EORTC QLQ-C30 global health status/quality of life composite scale in all randomized participants. The QLQ-C30 is a cancer-specific, self-administered questionnaire that contains 30 questions, covering global, functional, and symptom scales. Scores range from 0 to 100. Higher scores on global and functional scales indicated better quality of life (QoL), while higher scores on the symptom scales indicated declining QoL.
  8. Intensive Therapy Study: (EU & EU reference countries only): Complete remission (CR) with bone marrow (BM) measurable residual disease (MRD) negativity in NPM1-m patients
    CR rate per ELN 2022 criteria per Investigator assessment with central BM MRD negativity
  9. Intensive Therapy Study: Overall survival (OS)
    OS
  10. Intensive Therapy Study: Descriptive statistics of Adverse Events (AEs)
    Assessed by NCI-CTCAE v5.0
  11. Intensive Therapy Study: Health-related patient-reported outcomes (PRO) assessments
    Health-related quality of life (HRQoL) was evaluated by EORTC QLQ-C30 global health status/quality of life composite scale in all randomized participants. The QLQ-C30 is a cancer-specific, self-administered questionnaire that contains 30 questions, covering global, functional, and symptom scales. Scores range from 0 to 100. Higher scores on global and functional scales indicated better quality of life (QoL), while higher scores on the symptom scales indicated declining QoL.
  12. Intensive Therapy Study: Area under the concentration-time curve (AUC) of ziftomenib
    To characterize the AUC of ziftomenib
  13. Intensive Therapy Study: Trough concentration (Ctrough) of ziftomenib
    To characterize the Ctrough of ziftomenib

Eligibility Criteria

Ages Eligible for Study(Adult, Older Adult)
Sexes Eligible for StudyAll
Accepts Healthy VolunteersNo
Inclusion Criteria
The following criteria apply to both the Nonintensive Therapy Study and the Intensive Therapy Study unless otherwise noted:
Age ≥18 years at time of signing the informed consent form.
Diagnosis of AML per the 2022 WHO Classification of Hematolymphoid Tumors (5th Edition).
Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2.
Adequate liver and kidney function according to protocol requirements.
A female of childbearing potential must agree to use adequate contraception from the time of screening through 180 days following the last dose of study intervention. A male with a female partner of childbearing potential must agree to use abstinence or adequate contraception from the time of screening through 90 days following the last dose of study intervention.
NONINTENSIVE THERAPY STUDY ONLY (VEN+AZA): 1. Documented NPM1-m. 2. Patients considered ineligible for Intensive Therapy defined by the following:
i. Age ≥75, OR
ii. Age \<75 with an ECOG performance status of 2 or cardiac, renal, or hepatic impairment per protocol criteria.
INTENSIVE THERAPY STUDY ONLY (7+3): 1. Documented NPM1-m or KMT2A-r (KMT2A-r patients with a partial tandem duplication are not eligible). 2. Documented FLT3 wild-type or ITD ratio \<0.05 OR ineligible to receive FLT3-targeted therapy (medically ineligible or mutation in which FLT3 inhibition is not SOC). Lack of access to an FLT3 inhibitor is not considered "ineligible" for FLT3-targeted therapy. 3. Ejection fraction of ≥50%. 4. Fit for Intensive Therapy per Investigator opinion. Key
Exclusion Criteria
Prior therapy for AML (except hydroxyurea or leukapheresis for WBC control).
Diagnosis of acute promyelocytic leukemia (APL), blast phase chronic myeloid leukemia, or isolated myeloid sarcoma.
Known history of BCR-ABL mutation.
History of other active concurrent malignancies prior to study entry except: 1. Basal cell skin cancer or localized squamous cell cancer of the skin 2. Previous malignancy confined and locally resected (or treated with other modalities) with curative intent 3. Prostate or breast cancer receiving adjuvant hormonal therapy.
Active central nervous system (CNS) involvement by AML.
Clinical signs/symptoms of leukostasis or white blood cells (WBC) \>25×10\^9/L prior to start of ziftomenib/placebo. Note: Hydroxyurea and/or leukapheresis are permitted to meet this criterion.
Known uncontrolled HIV infection or known active hepatitis B virus, hepatitis C virus infection, or other uncontrolled infection.
Uncontrolled intercurrent illness including but not limited to, cardiac illness as defined in the protocol.
Women who are pregnant or lactating.

Contacts and Locations

Sponsors and CollaboratorsKura Oncology, Inc.
Locations
Banner MD Anderson Cancer Center | Gilbert Arizona, United States, 85234University of California, Fresno | Clovis California, United States, 93611University of California, San Diego | La Jolla California, United States, 92093Cedars-Sinai Medical Center | Los Angeles California, United States, 90048University of California, Los Angeles | Los Angeles California, United States, 90095University of California, Irvine | Orange California, United States, 92868University of Colorado | Aurora Colorado, United States, 80045Colorado Blood Cancer Institute | Denver Colorado, United States, 80218Hartford HealthCare Cancer Institute | Hartford Connecticut, United States, 06106Yale University School of Medicine | New Haven Connecticut, United States, 06510University of Miami | Miami Florida, United States, 33136Moffitt Cancer Center & Research Institute | Tampa Florida, United States, 33612University of Iowa | Iowa City Iowa, United States, 52246University of Kentucky | Lexington Kentucky, United States, 40536University of Massachusetts | Worcester Massachusetts, United States, 01605University of Michigan | Ann Arbor Michigan, United States, 48109Wayne State University School of Medicine | Detroit Michigan, United States, 48201University of Minnesota | Minneapolis Minnesota, United States, 55455Rutgers Biomedical and Health Sciences | New Brunswick New Jersey, United States, 08903University of New Mexico | Albuquerque New Mexico, United States, 87131State University of New York at Buffalo | Buffalo New York, United States, 14263Icahn School of Medicine at Mount Sinai | New York New York, United States, 10003Columbia University | New York New York, United States, 10032Weill Cornell Medical Center | New York New York, United States, 10065University of North Carolina, Chapel Hill | Chapel Hill North Carolina, United States, 27514Duke University Medical Center | Durham North Carolina, United States, 27710Ohio State University | Columbus Ohio, United States, 43210Willamette Valley Cancer Institute | Eugene Oregon, United States, 97401University of Pennsylvania | Philadelphia Pennsylvania, United States, 19104Baptist Clinical Research Institute | Memphis Tennessee, United States, 38120Tennessee Oncology | Nashville Tennessee, United States, 37203TriStar Centennial Medical Center | Nashville Tennessee, United States, 37203Texas Oncology-Austin Midtown | Austin Texas, United States, 78705Texas Oncology-Presbyterian Cancer Center | Dallas Texas, United States, 75231University of Texas | Houston Texas, United States, 77030Texas Oncology - San Antonio Medical Center | San Antonio Texas, United States, 78240University of Vermont Medical Center | Burlington Vermont, United States, 05401University of Virginia School of Medicine | Charlottesville Virginia, United States, 22903Virginia Cancer Specialists | Manassas Virginia, United States, 20110WVU Medicine Wheeling Hospital | Wheeling West Virginia, United States, 26003University of Wisconsin | Madison Wisconsin, United States, 53792Froedtert & Medical College of Wisconsin | Milwaukee Wisconsin, United States, 53226Calvary Mater Newcastle | Waratah New South Wales, Australia, 02298Box Hill Hospital | Heidelberg Victoria, Australia, 3128Fiona Stanley Hospital | Murdoch Western Australia, Australia, 6150Universitair Ziekenhuis Brussel | Jette Brussels Capital, Belgium, 1090Universitair Ziekenhuis Gent | Ghent Oost-Vlaanderen, Belgium, 9000Centre Hospitalier Régional Verviers East Belgium | Verviers Walloonia, Belgium, 4800Algemeen Ziekenhuis Sint-Jan Brugge | Bruges West-Vlaanderen, Belgium, 8800Algemeen Ziekenhuis Delta VZW | Roeselare West-Vlaanderen, Belgium, 8800Royal Victoria Hospital | Montreal Quebec, Canada, H4A3J1Fakultni Nemocnice Ostrava | Ostrava-Poruba Moravian-Silesian, Czechia, 70852Fakultní Nemocnice Královské Vinohrady | Prague Prague, Czechia, 10034Centre Hospitalier Universitaire Estaing - Clermont-Ferrand | Clermont-Ferrand Auvergne-Rhône-Alpes, France, 63003Hôpital Lyon Sud | Pierre-Bénite Auvergne-Rhône-Alpes, France, 69495Centre Hospitalier Universitaire de Saint Etienne | Saint-Priest-en-Jarez Auvergne-Rhône-Alpes, France, 42270Groupe Hospitalier de la Region de Mulhouse et Sud Alsace Hôpital Emile Muller | Mulhouse Grand Est, France, 68100Centre Hospitalier Régional et Universitaire de Nancy Hôpitaux de Brabois | Vandœuvre-lès-Nancy Grand Est, France, 54510Centre Hospitalier Universitaire de Nantes | Nantes Loire-Atlantique, France, 44000Centre Hospitalier Universitaire de Bordeaux | Pessac New Aquitaine, France, 33604Centre Hospitalier de Roubaix | Lille Nord, France, 59000Centre Henri Becquerel | Rouen Normandy, France, 76038Centre Hospitalier de Béziers | Béziers Occitanie, France, 35400Centre Hospitalier Universitaire de Marseille - Hôpital de la Conception | Marseille Provence-Alpes-Côte d'Azur Region, France, 13385Hôpital Universitaire Henri Mondor | Créteil Val-de-Marne, France, 94010Institut Gustave Roussy | Villejuif Val-De-Marne, France, 94805Hôpital Avicenne | Bobigny Île-de-France Region, France, 93009Centre Hospitalier de Versailles | Le Chesnay Île-de-France Region, France, 78150Hôpital Saint Louis | Paris Île-de-France Region, France, 75010Hôpital Pitié-Salpêtrière | Paris Île-de-France Region, France, 75013Helios Klinikum Bad Saarow | Bad Saarow Brandenburg, Germany, 15526Universitätsklinikum Aachen | Aachen North Rhine-Westphalia, Germany, 52074Laiko General Hospital of Athens | Athens Attica, Greece, 11527Attikon University General Hospital of Athens | Chaïdári Attica, Greece, 12462General Hospital of Thessaloniki G. Papanikolaou | Exochi Central Macedonia, Greece, 57010University General Hospital of Alexandroupoli | Alexandroupoli East Macedonia and Thrace, Greece, 68100University General Hospital of Ioannina | Ioannina Epirus, Greece, 45500L'IRCCS Azienda Ospedaliero - Universitaria di Bologna | Bologna Emilia-Romagna, Italy, 40138Hospital Santa Maria delle Croci | Ravenna Emilia-Romagna, Italy, 48121ASUGI Ospedale Maggiore di Trieste | Trieste Friuli Venezia Giulia, Italy, 76038ASST Spedali Civili di Brescia | Brescia Lombardy, Italy, 25123Azienda Sanitaria Territoriale di Ascoli Piceno | Ascoli Piceno The Marches, Italy, 63100Azienda Ospedaliero-Universitaria | Perugia Umbria, Italy, 42270Baguio General Hospital and Medical Center | Baguio City Benguet, Philippines, 02600University of Santo Tomas | Manila National Capital Region, Philippines, 1015The Medical City | Pasig National Capital Region, Philippines, 1605St. Luke's Medical Center - Quezon City | Quezon City National Capital Region, Philippines, 1112Szpital Wojewodzki w Opolu | Opole Opole Voivodeship, Poland, 45-061Hospital de Braga, Centro Clínico Académico de Braga | Braga , Portugal, 1099-023Chungnam National University Daejeon Hospital | Daejeon Daejeon Gwang'Yeogsi, South Korea, 35015Daegu Catholic University Hospital | Daegu Gyeongsangbuk-do, South Korea, 42472Pusan National University Hospital | Busan-si Gyeongsangnam-do, South Korea, 49241Dong-A University Hospital | Pusan Gyeongsangnam-do, South Korea, 49201Ulsan University Hospital | Ulsan Gyeongsangnam-do, South Korea, 44033Gachon University Gil Medical Center | Namdong Incheon Gwang'Yeogsi, South Korea, 21565Chonnam National University Hwasun Hospital | Hwasun Jeollanam-do, South Korea, 58128Anam Hospital Korea University | Seoul Seoul-T'Ukpyolsi, South Korea, 02841The Catholic University of Korea Seoul St. Mary's Hospital | Seoul Seoul-T'Ukpyolsi, South Korea, 06591Samsung Medical Center | Seoul Seoul-T'Ukpyolsi, South Korea, 35015University Hospital Virgen Del Rocio S.L. | Seville Andalusia, Spain, 41013Hospital Clinico Universitario Lozano Blesa | Zaragoza Aragon, Spain, 50009Hospital Universitario De Burgos | Burgos Castille and León, Spain, 09006Hospital General Universitario de Albacete | Albacete Castille-La Mancha, Spain, 02006Hospital Universitario Infanta Leonor | Madrid Madrid, Spain, 28031Hospital Universitario Fundación Jiménez Díaz | Madrid Madrid, Spain, 28040Hospital Universitario 12 de Octubre | Madrid Madrid, Spain, 28041Hospital Universitario Central de Asturias | Oviedo Principality of Asturias, Spain, 33011Hospital Clinico Universitario de Valencia | Valencia València, Spain, 46010Hospital Universitario Y Politecnico La Fe | Valencia València, Spain, 46026Chang Bing Show Chwan Memorial Hospital | Lugang Central Taiwan, Taiwan, 505Taichung Veterans General Hospital | Taichung Central Taiwan, Taiwan, 407National Taiwan University Hospital | Taipei Northern Taiwan, Taiwan, 10002Taipei Veterans General Hospital | Taipei Northern Taiwan, Taiwan, 613St. Bartholomew's Hospital | London England, United Kingdom, EC1A 7BESt. George's, University of London | London England, United Kingdom, SW17 0QT