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 /2 study of KO-539 in patients with relapsed or refractory acute myeloid leukemia (AML).
The goal of Phase 1 is to determine the safety, tolerability, pharmacokinetics, and recommended phase 2 dose (RP2D) of KO-539.
The goal of the Phase 2 registration-enabling expansion in specific genetic subgroups is to further evaluate anti-tumor activity and tolerability of KO-539.
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 mutations5,6
STUDY LOCATIONS
Please select a location to see sites near you
For more information, please email:
KO-MEN-001@kuraoncology.com.
To connect 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.