Kura Oncology, a San Diego biopharmaceutical company, was recently featured in a Globe Newswire article, announcing its first-in-human dose escalation of KO-539 being evaluated in the Komet-001 trial (NCT04067336).
The trial data generated for the menin inhibitor, KO-539, suggests potential efficacy for certain relapsed and refractory (not responding to treatment) AML subgroups.
About the Trial
The clinical trial, KOMET-001, is a Phase 1/2A study of Kura’s oral menin inhibitor, KO-539, that enrolled twelve patients, each with relapsed or refractory AML.
Of the twelve patients, eight patients were accepted for evaluation and inclusion in the study.
The participants were split into four groups according to dosing. The cohorts were dosed orally with KO-539 once daily and in twenty-eight-day cycles as follows: fifty, one hundred, two hundred, and four hundred milligrams.
All those participating had been treated unsuccessfully with two to seven prior therapies.
Six of the eight participants who were evaluated included:
- A patient with the NPM1 mutation. About thirty percent of adult AML patients are found to have NPM1 genetic mutation. This patient, dosed at two hundred milligrams, responded with complete remission and no evidence of residual disease.
- Another patient with NPM1 plus co-mutations TET2, CUX1, and FLT3-ITD was judged to be in a morphological leukemia-free state after being treated unsuccessfully with four prior therapies. The second patient was also dosed at two hundred milligrams of KO-539.
- A third patient diagnosed with RUNX1 and SETD2 co-mutations achieved a complete response after only two cycles of KO-539. The patient’s dose was increased from one hundred to two hundred milligrams when, at cycle number seven, blast counts increased. The patient had clinical benefits for six months prior to the increase in blast counts.
- The fourth patient’s peripheral blood count stabilized while still at a dose of fifty milligrams (the starting dose). This patient was diagnosed with KMT2A/MLL rearrangement (structural alteration). The patient had a significant decrease in the need for hydroxyurea, a drug that decreases the level of white blood cells in AML.
KO-539’s Safety Profile
Kura reports that KO-539’s safety profile has been manageable, and the daily dosing is well tolerated. Further, there were no reports of patients discontinuing KO-539 due to adverse events related to treatment.
With respect to EKGs, there were no significant changes or prolongation of QTs, which is the length of time it takes the heart to recharge between beats.
Adverse events greater than grade 3 related to treatment included decreased neutrophil count, deep venous thrombosis, pancreatitis, or increased lipase (enzyme).
Kura anticipates determining the maximum recommended Phase 2 dose in early 2021. At that time the company plans to advance into select patient populations where KO-539 could be most beneficial.
The FDA granted KO-539 Orphan Drug status for the treatment of patients with AML. This designation allows certain financial and exclusivity incentives. It is usually granted for products intended to treat rare diseases or conditions.
About AML (Acute Myeloid Leukemia)
The first evidence of AML is abnormal white and/or red blood cells and platelets. AML is a common type of leukemia with a poor prognosis. This is especially true for patients who have either leukemia that does not respond to treatment (refractory) or relapsed AML.
Kura Oncology, San Diego, California
Kura Oncology is a biopharmaceutical company that has joined the genetic revolution. Kura realizes that a patient’s response to treatment depends on his or her cancer’s genetic identity. Kura’s product pipeline includes two small molecule drugs that target cancer’s signaling pathways.
Additionally, Kura’s pipeline carries KO-539, an inhibitor of menin-KMT2A/MLL being investigated in the KOMET-001 clinical trial for relapsed or refractory AML patients.
Data from the KOMET-001 trial are being presented at the virtual session of the 62nd ASH Exposition and Annual Meeting held in early December 2020.
