A Menin Inhibitor Study

Now enrolling patients with refractory or relapsed AML

About KOMET-001

KOMET-001 (Kura Oncology Menin Inhibitor Trial) is a phase 1/2a study to determine the safety, tolerability, and recommended phase 2 dose (RP2D) of KO-539 in patients with refractory or relapsed acute myeloid leukemia (AML).

An expansion phase in specific genetic subgroups will further evaluate antitumor activity and tolerability.

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Study locations

ABOUT KO-539

KO-539, an oral investigational drug candidate, is a novel compound targeting the menin-KMT2A (MLL) interaction for treatment of genetically defined AML patients with high unmet need. In preclinical models, KO-539 inhibits the KMT2A (MLL) protein complex and has downstream effects on HOXA9/MEIS1 expression.

Epigenetic modifications by the menin-KMT2A (MLL) complex lead to expression of HOXA9/MEIS1, which leads to proliferation, stemness, and differentiation block.¹
These KMT2A (MLL) rearrangements alter normal histone methyltransferase function of KMT2A (MLL), resulting in sustained high HOX levels and blockage of hematopoietic differentiation, ultimately leading to acute leukemia.^1-3
Mutant NPM1 is also dependent on the interaction between menin and wild-type KMT2A (MLL) to drive leukemogenic gene expression.¹
KO-539 is an investigational small molecule inhibitor of menin-KMT2A (MLL) complex that may inhibit the survival, growth, and proliferation of certain kinds of leukemia cells as demonstrated in vitro.⁴

AML Mutations

~5-10%

of AML patients have translocations
of the KMT2A gene²

25-30%

of AML patients have NPM1 mutations
with or without other gene mutations^5,6

Study Overview Patient Criteria Outcome Measures

KOMET-001 is a phase 1/2a open-label study to determine safety, tolerability, maximum tolerated dose (MTD), and/or RP2D of KO-539 in patients with relapsed and/or refractory AML.
Once the RP2D is established, an expansion phase with specific genetically defined subgroups will begin. The first cohorts planned are:
- NPM1 mutant AML cohort
- KMT2A rearranged AML cohort
Trial number: KO-MEN-001
ClinicalTrials.gov Identifier: NCT04067336

Key Inclusion Criteria

Refractory or relapsed AML defined as the reappearance of >5% blasts in the bone marrow and who have failed or are ineligible for any approved standard of care therapies, including hematopoietic stem cell transplantation (HSCT).
At least 18 years of age.
Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.
Adequate organ function.
Concomitant use of antibiotics, antifungals, and antivirals that are used as standard of care or to prevent or treat infections are allowed. Patients who require treatment with concomitant drugs that are strong inhibitors or inducers of cytochrome P450-isozyme 3A4 (CYP3A4) for other reasons will be excluded.
Hydroxyurea will be allowed prior to enrollment and after the start of KO-539 to control and maintain peripheral white blood cell (WBC) counts ≤30,000/µL. Patients can continue on hydroxyurea through Cycle 1 Day 28 or until first disease assessment. After which, patients should be titrated off therapy.

For full details of inclusion and exclusion criteria, please visit clinicaltrials.gov

Objectives of the Phase 1 Portion

Safety and tolerability
Determine MTD and/or RP2D
Pharmacokinetics
Early evidence of antitumor activity

Objectives of the Phase 2a Portion

Antitumor activity
Safety and tolerability

For full details of outcomes measure, please visit clinicaltrials.gov.

STUDY LOCATIONS

Please select a location to see sites near you

United States, Illinois
Northwestern University
Chicago, Illinois, United States, 40411

United States, Massachusetts
Massachusetts General Hospital
Boston, Massachusetts, United States, 02114

United States, Michigan
University of Michigan Hospitals
Ann Arbor, Michigan, United States, 48109

United States, New York
Roswell Park Comprehensive Cancer Center
Buffalo, New York, United States, 14263

United States, Washington
Fred Hutchinson Cancer Research Center
Seattle, Washington, United States, 98109

France
Institut Gustave Roussy
Villejuif, France, 94800

For more information, please email:
KO-MEN-001@kuraoncology.com.

To talk with a medical science liaison (MSL), please email: medicalaffairs@kuraoncology.com.

REFERENCES: 1. Kühn MW, Song E, Feng Z et al. Targeting Chromatin Regulators Inhibits Leukemogenic Gene Expression in NPM1 Mutant Leukemia. Cancer Discov. 2016;6(10):1166–1181. 2. Klossowski S, Miao H, Kempinska K, et al. Menin inhibitor MI-3454 induces remission in MLL1-rearranged and NPM1-mutated models of leukemia. J Clin Invest. 2020;130(2):981-997. 3. Chan AKN, Chen CW. Rewiring the Epigenetic Networks in MLL-Rearranged Leukemias: Epigenetic Dysregulation and Pharmacological Interventions. Front Cell Dev Biol. 2019;7:81. 4. Burrows F, Wu T, Kessler L, et al. A novel small molecule menin-MLL inhibitor for potential treatment of MLL-rearranged leukemias and NPM1/DNMT3A-mutant AML [abstract]. In: Proceedings of the AACR EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2017 Oct 26-30; Philadelphia, PA. Philadelphia (PA): AACR; Mol Cancer Ther 2018;17(1 Suppl): Abstract nr LB-A27. 5. Thiede C, Koch S, Creutzig E, et al. Prevalence and prognostic impact of NPM1 mutations in 1485 adult patients with acute myeloid leukemia (AML). Blood. 2006;107(10):4011-4020. 6. 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.

A Menin Inhibitor Study

About KOMET-001

ABOUT KO-539

AML Mutations

~5-10%

25-30%

Key Inclusion Criteria

Objectives of the Phase 1 Portion

Objectives of the Phase 2a Portion

STUDY LOCATIONS

Fred Hutchinson Cancer Research Center

Hopital Saint Louis

Institut Gustave Roussy

Massachusetts General Hospital

MD Anderson Cancer Center

Northwestern University

Roswell Park Comprehensive Cancer Center

University of Michigan Hospitals

Address