FDA Lifts Partial Clinical Hold from KOMET-001 in R/R AML


The KOMET-001 study may resume after the FDA lifted the partial clinical hold for safety.

A partial clinical hold has been lifted from the phase 1b KOMET-001 clinical trial of KO-539 in patients with relapsed or refractory acute myeloid leukemia (AML), according to a press release by Kura Oncology, Inc.1

Originally, the FDA placed the partial clinical hold due to a patient death from a grade 5 adverse event (AE), that was thought to have been associated with differentiation syndrome, which occurs sometimes with differentiating agents administered to patients with AML.2

“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,” said Troy Wilson, PhD, JD, president and chief executive officer of Kura Oncology, in a press release.1 “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 KOMET-001 study is a first-in-human, open-label, dose-escalation, and dose-validation/expansion study (NCT04067336). In a preliminary analysis, KO-539 showed promising early biologic activity in relapsed AML, which was considered to be promising. The pharmacokinetic profile of KO-539 signaled potential clinical benefit.3 Further, data from 3 patients showed no dose-limiting toxicities within a 28-day window. Grade 3 or higher drug-related AEs included grade tumor lysis syndrome at the 50-mg dose level and a grade 3 embolic event at the 100-mg dose level. Overall KO-539 was well-tolerated in the small group of patients with no dose reductions or discontinuations required.4

The goal of KOMET-001 is to determine the safety and preliminary activity of KO-539, a menin-MLL (KMT2A) inhibitor. The coprimary end points of the study include determining the maximum tolerated dose of the agent, the number of patients who experience AEs, and finding the minimal biologically effective dose. The key secondary end points of the study are the number of patients with AEs or serious AEs, complete response rate, duration of response, transfusion independence, relapse-free survival, and overall survival.3

Approximately 90 patients will be enrolled. Patients are required to be at least 18 years old with relapsed or refractory AML, an ECOG performance status of 0 to 2, adequate kidney and liver function, peripheral white blood cell counts ≤ 30,000/μL, and who are willing to use contraception throughout the study.


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 24, 2022. https://bit.ly/3qWSzNP

2. Kura Oncology provides update on phase 1b study of KO-539 in acute myeloid leukemia. News release. Kura Oncology. November 24, 2021. Accessed November 24, 2021. https://bit.ly/3HJKG4N

3. First in human study of KO-539 in relapsed or refractory acute myeloid leukemia. Clinicaltrials.gov. Accessed November 24, 2021. https://bit.ly/3l2e3Wk

4. Wang ES, Altman JK, Pettit KM, et al. 115 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. Presented at: 2020 ASH Annual Meeting and Exposition; resented at: 2020 ASH Annual Meeting & Exposition; December 4-8, 2020; Virtual. Abstract 115.

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