First in Human Study of KO-539 in Relapsed or Refractory Acute Myeloid Leukemia

• Status: Recruiting
• Trial end date: 2022-08-01
• Target enrollment: 0
• Participant gender: All

Summary

This first-in-human (FIH) dose-escalation and dose-validation/expansion study will assess KO-539, a menin-MLL(KMT2A) inhibitor, in patients with refractory or relapsed acute myeloid leukemia (AML).

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Kura Oncology, Inc.

Criteria

Key Inclusion Criteria:

1. Refractory or relapsed AML defined as the reappearance of > 5% blasts in the bone marrow and who have also failed or are ineligible for any approved standard of care therapies, including HSCT.

2. ≥ 18 years of age.

3. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.

4. Adequate liver and kidney function according to protocol requirements.

5. Peripheral white blood cell (WBC) counts ≤ 30,000/μL. Patients are allowed to receive hydroxyurea to control and maintain WBC count prior to enrollment.

6. Both men and women (of childbearing potential) enrolled in this trial must use adequate birth control measures during the course of the trial and for at least 90 days after their last dose of study treatment.

Key Exclusion Criteria:

1. Donor lymphocyte infusion < 30 days prior to study entry.

2. Clinically active central nervous system (CNS) leukemia.

3. Undergone HSCT and have not had adequate hematologic recovery (i.e. ANC >1000 and platelet count > 100,000).

4. Receiving immunosuppressive therapy post HSCT at the time of screening (must be off all immunosuppression therapy for at least 2 weeks). The use of topical steroids for cutaneous GVHD is allowed and stable steroid doses less than or equal to 20 mg of prednisone daily is permitted.

5. Grade > 2 active graft-versus-host disease (GVHD), moderate or severe limited chronic GVHD, or extensive chronic GVHD of any severity.

6. Received chemotherapy immunotherapy, or radiotherapy or any ancillary therapy that is considered to be investigational (i.e., used for non-approved indications(s) and in the context of a research investigation) < 14 days prior to the first dose of KO-539 or within 5 drug half-lives (whichever is longer) prior to the first dose of study drug.

7. Treatment with concomitant drugs that are strong inhibitors or inducers of cytochrome P450-isozyme 3A4 (CYP3A4) with the exception of antibiotics, antifungals, and antivirals that are used as standard of care or to prevent or treat infections and other such drugs that are considered absolutely essential for the care of the patient.

8. Known detectable viral load for human immunodeficiency virus, hepatitis C, or hepatitis B surface antigen indicative of active infection.

9. Active uncontrolled acute or chronic systemic fungal, bacterial, viral, or other infection.

10. Significant cardiovascular disease including unstable angina pectoris, uncontrolled hypertension or arrhythmia, history of cerebrovascular accident including transient ischemic attack within the past 6 months, congestive heart failure (NYHA Class III or IV) related to primary cardiac disease, ischemic or severe valvular heart disease, or a myocardial infarction within 6 months prior to the first dose of study treatment.

11. QTcF >480 ms.

12. Major surgery within 4 weeks prior to the first dose of study treatment.

13. Women who are pregnant or lactating. All female patients with reproductive potential must have a negative pregnancy test prior to starting treatment.