FDA Lifts Partial Clinical Hold on Early-Phase Study of KO-539 in AML


The phase 1b KOMET-001 trial, examining the use of KO-539 in patients with relapsed or refractory acute myeloid leukemia, will continue following authorization from the FDA.

The FDA has lifted a partial clinical hold that was placed on the phase 1b KOMET-001 trial (NCT04067336) assessing the use of KO-539 in patients with relapsed/refractory acute myeloid leukemia, according to a press release from developer Kura Oncology.1

The hold was lifted after the FDA came to an agreement on a strategy for mitigating differentiation syndrome, which commonly occurs with the use of differentiating agents that are used in AML. In light of this, investigators will continue screening and enrolling patients on the study.

“I am very proud of our team for working diligently with the FDA and site investigators to resolve the partial clinical hold in such a timely manner,” Troy Wilson, PhD, JD, president and chief executive officer at Kura Oncology, said in a press release. “Activities to resume patient screening are underway, and we look forward to expediting enrollment of patients in the phase 1b study and determining the recommended phase 2 dose for KO-539 in the coming months. Meanwhile, we continue to be encouraged by the safety, tolerability, and clinical activity observed among currently enrolled patients and look forward to sharing a comprehensive update on the phase 1 study at a future medical meeting.”

The partial clinical hold was implemented in November 2021 following a report to the FDA regarding the possibility of a grade 5 serious adverse effect that was potentially associated with the use the differentiating agent.2 Although no patients were to be enrolled until the partial clinical hold was resolved, patients who already enrolled continued to receive treatment.

KOMET-001 is a first in human trial assessing the safety and efficacy of a menin-KMT2A inhibitor in a population of patients with relapsed/refractory disease.3 Investigators note that KMT2A plays a role in regulating expression in the HOX and MEIS1 genes in addition to impacting epigenetic dysregulation in AMLM containing co-mutations, including NPM1, IDH1/2, EZH2, and DNMT3A. This provided the rationale for utilizing a menin-KMT2A inhibitor within this patient population.

A total of 6 patients were enrolled as of the August 10, 2020, data cut off. The dose-escalation portion of the study started with a dose of 50 mg and went up to 200 mg. Notably, 3 patients were included in a 200 mg expansion cohort to better characterize pharmacokinetics and treatment exposure.

Investigators reported that KO-539 demonstrated promising biologic activity across the first 3 dose levels.

“The early biologic activity of KO-539 in relapsed AML is encouraging, and its unique PK [pharmacokinetic] characteristics may be advantageous for clinical benefit. In addition to the above, any updated safety, PK, and efficacy data will be presented at the time of the conference,” the investigators concluded


  1. Kura Oncology receives FDA authorization to proceed with phase 1b study of KO-539 in acute myeloid leukemia. News release. Kura Oncology. January 20, 2022. Accessed January 21, 2022. https://bit.ly/35dB1og
  2. Kura Oncology provides update on phase 1b study of KO-539 in acute myeloid leukemia. News release. Kura Oncology. November 24, 2021. Accessed January 21, 2022. https://bit.ly/3nLIHoc
  3. Wang ES, Altman JK, Pettit K, et al. Preliminary Data on a Phase 1/2A First in Human Study of the Menin-KMT2A (MLL) Inhibitor KO-539 in Patients with Relapsed or Refractory Acute Myeloid Leukemia. Blood. 2020;136(suppl 1):7-8. doi:10.1182/blood-2020-134942
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