FDA Halts KOMET-001 Study for Acute Myeloid Leukemia Due to Safety


The phase 1b KOMET-001 has been suspended while the developer of KO-539 and FDA investigate a serious safety event.

The FDA has placed a partial clinical hold on the phase 1b KOMET-00 study, which was evaluating treatment with KO-539 in patients with relapsed or refractory acute myeloid leukemia (AML), according to a press release issued by Kura Oncology, Inc.1

The FDA’s action was based on a patient death caused by a grade 5 adverse event (AE). The event may have been associated with differentiation syndrome, which occurs sometimes with differentiating agents administered to patients with AML. The trial may continue following an investigation.

“We share the FDA’s commitment to patient safety, and we appreciate our ongoing dialogue as we work diligently to address their questions,” said Troy Wilson, PhD., JD, president, and chief executive officer of Kura Oncology, in a press release “Differentiation syndrome is known to be an on-target effect associated with therapeutic agents that induce differentiation, and we want to ensure physicians are fully informed and prepared to address these events if they occur. Based on the totality of preclinical and clinical data, we continue to believe that KO-539 has the potential to address the significant unmet medical need of AML patients, including those with NPM1 mutations and KMT2A rearrangements.”

KOMET-001 study is a first-in-human, open-label, dose-escalation, and dose-validation/expansion study (NCT04067336). The goal of that study 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 study’s key secondary end points include the number of patients with AEs or serious AEs, complete response rate, duration of response, transfusion independence, relapse-free survival, and overall survival.2

The study aims to enroll 90 patients total who are 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.

In a preliminary analysis, the early biologic activity of KO-539 in relapsed AML was considered to be promising. Moreover, the pharmacokinetics of the agent suggested potential clinical benefit.3

Data from 3 patients showed no dose-limiting toxicities with a 28-day window. In terms of safety, cases of grade 3 or higher drug-related AEs have 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.

Since the death of the patient in KOMET-001, no more patients can be enrolled in the study. But, patients already enrolled will continue to be treated. Further, the company has decided to suspend guidance on the completion of enrollment in the study and the determination of the recommended phase 2 dose of KO-539. Kura Oncology will work closely with the FDA to resolve the partial clinical hold.1


1. 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

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

3. 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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