Studies testing Ziftomenib together with standard treatments in adults with newly diagnosed acute myeloid leukemia (AML) that has specific genetic changes (NPM1 or KMT2A)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Kura Oncology Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

19 Mar 2026 → ongoing

Decision date (initial)

2026-02-25

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

No

Funding sources

Kura Oncology, Inc.

External identifiers

EU CT number

2025-521314-25-00

ClinicalTrials.gov

NCT07007312

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Pharmacokinetic, Therapy, Safety

Nonintensive Therapy Study
- To evaluate the effect of ziftomenib combined with SOC ven+aza on patient survival in untreated NPM1 m AML
Intensive Therapy Study (7+3)
- To evaluate the effect of ziftomenib combined with SOC 7+3 on patient EFS in untreated NPM1 m and KMT2A-r AML

Secondary objectives 1

1. Nonintensive Therapy Study - To determine the efficacy of ziftomenib combined with SOC ven+aza in untreated NPM1 m AML - To determine the rate of MRD negativity achieved with ziftomenib combined with SOC ven+aza in untreated NPM1 m AML - To evaluate CR/CRh as an additional measure of efficacy of ziftomenib in combination with SOC ven+aza in untreated NPM1 m AML Intensive Therapy Study (7+3) - To determine the efficacy of ziftomenib combined with SOC 7+3 in untreated NPM1 m AML - To evaluate the effect of ziftomenib combined with SOC 7+3 on patient survival in untreated NPM1 m and KMT2A-r AML

Conditions and MedDRA coding

NPM1-m and KMT2A-r Acute Myeloid Leukemia

Study design 2 periods

Regulatory references

Scientific advice from competent authorities

European Medicines Agency, Food And Drug Administration

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 12

1. 1. Age ≥18 years at time of signing the informed consent form (ICF).
2. 2. Diagnosis of AML per the 2022 WHO Classification of Hematolymphoid Tumors (5th Edition).
3. 3. Patients with therapy-related AML (t-AML) or secondary AML (prior myelodysplastic syndrome [MDS] or myeloproliferative neoplasm [MPN]) are eligible. 1. Note: Prior MDS eligibility requires that at the time of MDS diagnosis the patient did not have evidence of either NPM1-m or KMT2A-r (now classified as AML by WHO 5th Edition).
4. 4. Patients with prior MDS who have received a single line of treatment with single agent HMA, lenalidomide, luspatercept, or imetelstat are eligible.
5. 5. Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2.
6. 6. Adequate liver function defined as: •AST <5×upper limit of normal (ULN), and •ALT <5×ULN, and • Total bilirubin <1.5×ULN (except for patients with known Gilbert’s syndrome or presumed leukemic involvement). Note: If the patient does not meet this criterion but the liver function abnormalities are presumed to be due to AML, this may be discussed with the Medical Monitor to determine eligibility.
7. 7. Adequate renal function defined by calculated creatinine clearance ≥30 mL/min (according to the 2021 Chronic Kidney Disease Epidemiology-Collaboration [CKD-EPI] creatinine equation).
8. 8. If the patient has comorbid illness, life expectancy attributed to this other condition(s) must be greater than 2 years in the opinion of the Investigator.
9. 9. Patient agrees to the following contraception requirements: a. A male patient is eligible to participate if they agree to the following during the study treatment period and for 180 days after the last dose of study treatment: • Refrain from donating sperm. plus, either: • Be abstinent from intercourse where pregnancy can occur (abstinent on a long term and persistent basis) and agree to remain abstinent. or • Agree to use highly effective contraception plus barrier as follows: o Use an external condom (barrier) with female partner of childbearing potential using additional highly effective contraceptive method with a failure rate of <1% per year as described in Appendix 2 when having sexual intercourse with a partner able to give birth who is not currently pregnant. plus o Use an external condom when engaging in any activity that allows for passage of ejaculate to another person. b. A female patient is eligible to participate if not pregnant or breastfeeding, and one of the following conditions applies: • Is of nonchildbearing potential as defined in Appendix 2. or • Is of childbearing potential as defined in Appendix 2 and agrees to the following during the study treatment period and for 180 days after the last dose of study treatment: o Agrees to use a contraceptive method that is highly effective (with a failure rate of <1% per year), preferably with low user dependency, as described in Appendix 2 in addition to male partner either using an external condom (barrier) or male partner confirmed azoospermic. plus o Agrees not to donate eggs (ova, oocytes) for the purpose of reproduction. Note: The Investigator should evaluate the potential for contraceptive method failure (eg, noncompliance or recently started) in relationship to the first dose of study treatment.
10. 10. Patients must be able to understand and provide informed consent, understand protocol requirements, and be willing to comply with study requirements, in the opinion of the Investigator.
11. 11. NONINTENSIVE THERAPY STUDY ONLY (VEN+AZA): a. Documented NPM1-m. b. Patients considered ineligible for IC defined by the following i. Age ≥75, OR ii. Age <75 and unfit for IC. Must meet one of these comorbidity exceptions which prevents them from being treated with IC: 1. ECOG performance status of 2, or 2. Cardiac history of congestive heart failure (CHF) requiring treatment or ejection fraction of ≤50% or chronic stable angina, or 3. Diffusing capacity of the lungs for carbon monoxide ≤65% or forced expiratory volume in 1 second ≤65%, or 4. Creatinine clearance <45 mL/min and >30 mL/min, or 5.Moderate hepatic impairment with total bilirubin 1.5 to 3.0×ULN, not related to AML involvement or Gilbert’s syndrome, or 6. Other comorbidities that, in the opinion of the Investigator, cause the patient to be incompatible with IC (prior approval by the Medical Monitor is required before enrollment).
12. 12. INTENSIVE THERAPY STUDY ONLY (7+3): a. Documented NPM1-m or KMT2A-r (patients with a partial tandem duplication [PTD] are not eligible). b. 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. c. Ejection fraction of >50% by transthoracic echocardiogram (ECHO) or multigated acquisition scan (MUGA). d. Fit for IC per Investigator opinion.

Exclusion criteria 13

1. 1. Diagnosis of either acute promyelocytic leukemia (APL), blast phase chronic myeloid leukemia, or isolated myeloid sarcoma. Note: Patients with myeloid sarcoma in addition to BM disease are eligible.
2. 2. Known history of BCR-ABL mutation.
3. 3. History of other active concurrent malignancies prior to study entry except: • Basal cell skin cancer or localized squamous cell cancer of the skin • Previous malignancy confined and locally resected (or treated with other modalities) with curative intent • Prostate or breast cancer receiving adjuvant hormonal therapy (see Section 7.5.1 for permitted medications)
4. 4. Active central nervous system (CNS) involvement by AML. Note: Those patients with evidence of CNS AML involvement at baseline/screening now controlled (cerebrospinal fluid [CSF] cleared and no symptoms) with intrathecal chemotherapy or those who are at high risk of developing CNS disease (including KMT2A-r, high white blood cells [WBC], high lactate dehydrogenase [LDH], presence of extramedullary disease [EMD]) may continue to receive intrathecal chemotherapy as treatment or prophylaxis, respectively, as per institutional practice.
5. 5. Clinical signs/symptoms of leukostasis or WBC >25×109/L prior to start of ziftomenib/placebo. Note: Hydroxyurea and/or leukapheresis are permitted to meet this criterion. Cytotoxic therapy in addition to the SOC protocol backbones (7+3 or ven+aza) is not permitted to manage leukocytosis.
6. 6. Prior therapy for AML (except hydroxyurea or leukapheresis for WBC control). Patients may have received ATRA if there is an early suspicion of APL. Patients with a confirmed diagnosis of APL are not eligible.
7. 7. Prior ven+HMA therapy, isocitrate dehydrogenase 1 inhibitor, or intensive chemotherapy for MDS. Note: Prior MDS treatment with either single agent HMA, lenalidomide, luspatercept, or imetelstat is allowed. Any of these agents for prior MDS treatment must have been discontinued ≥14 days prior to Cycle 1 Day 1.
8. 8. Known uncontrolled HIV infection or known active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection. Viral serologies for HIV, HBV, HCV are not required. However, for patients with a known medical history of HIV/HBV/HCV infection, an undetectable viral load must be confirmed. Patients with serologic evidence of prior vaccination to HBV (HBV surface antigen negative and anti-HBV surface antibody positive) may participate.
9. 9. Any other significant ongoing medical condition, including psychiatric illness or laboratory abnormality, that would preclude the patient from participating in the study or would confound the interpretation of the results of the study in the opinion of the Investigator.
10. 10. Diagnosis with any of the following per Investigator opinion: uncontrolled intercurrent illness including but not limited: • Symptomatic CHF • Unstable angina pectoris • Serious cardiac arrhythmia • Myocardial infarction with evidence of residual abnormalities within 6 months prior to enrollment (troponin leak alone not included if no residual dysfunction) • New York Heart Association Class III or IV heart failure • Severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia • Mean QTcF >480 ms on triplicate ECGs Note: If a patient has bundle branch block or QRS >120 ms, the QTcF must be either calculated by cardiology, calculated using a QTc calculator (eg, the Mayo Clinic QTc calculator [https://www.mayoclinic.org/medical-professionals/cardiovascular-diseases/calculators/corrected-qt-interval-qtc-calculator/itt-20487211]), or calculated using the Boghossian simplified formula (QTc=QT-0.5*QRS).
11. 11. Diagnosis of an uncontrolled infection. Note: Patients with an active infection may be eligible provided that the infection is controlled by appropriate antimicrobial therapy in the opinion of the Investigator.
12. 12. Known severe hypersensitivity to the product or similar chemical structure and class to the study drugs evaluated in this study or 1 of the active or inactive excipients.
13. 13. Women who are pregnant or breastfeeding.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Nonintensive Therapy Study - Overall survival (OS) Intensive Therapy Study (7+3) - EFS, defined as the time from randomization to treatment failurea, hematologic relapse following CR, or death from any cause, whichever comes first

Secondary endpoints 2

1. Nonintensive Therapy Study - CR rate per the ELN 2022 criteria per Investigator assessment - Percentage of patients achieving centrally defined BM MRD negativity - Rates of CR+CRh per ELN 2022 per Investigator assessment
2. Intensive Therapy Study (7+3) - Percentage of patients achieving CR per ELN 2022 criteria with centrally defined BM MRD negativity (CRMRD-) - Overall survival (OS)

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 8

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Kura Oncology Inc.

Sponsor organisation

Kura Oncology Inc.

Address

12730 High Bluff Drive Suite 400

City

San Diego

Postcode

92130-2079

Country

United States

Scientific contact point

Organisation

Kura Oncology Inc.

Contact name

Kura Oncology Inc.

Public contact point

Organisation

Kura Oncology Inc.

Contact name

Kura Oncology Inc.

Third parties 11

Locations

10 EU/EEA countries · 92 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 107 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

4 submissions — initial application plus substantial / non-substantial modifications