NCT05441514

Enasidenib in Combination With Cobimetinib for the Treatment of Relapsed or Refractory Acute Myeloid Leukemia

Phase 1b Study of IDH Inhibition With Enasidenib and MEK Inhibition With Cobimetinib in Patients With Relapsed or Refractory Acute Myeloid Leukemia Who Have Co-Occurring IDH2 and RAS Signaling Gene Mutations

• Status: Active Not Recruiting
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 3 (actual)
• Sponsor: City of Hope Medical Center · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This phase Ib trial tests the safety, side effects, and best dose of a enasidenib in combination with cobimetinib in treating patients with acute myeloid leukemia that has come back (relapsed) or does not respond to treatment (refractory). Enasidenib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Cobimetinib is used in patients whose cancer has a mutated (changed) form of a gene called BRAF. It is in a class of medications called kinase inhibitors. It works by blocking the action of an abnormal protein that signals cancer cells to multiply. This helps slow or stop the spread of cancer cells. Giving enasidenib and cobimetinib may kill more cancer cells in patients with relapsed or refractory acute myeloid leukemia.

Detailed description

PRIMARY OBJECTIVES: I. Assess the safety and tolerability of cobimetinib in combination with enasidenib. II. Determine the maximum tolerated dose(s) (MTD) and recommended phase 2 dose (RP2D). SECONDARY OBJECTIVES: I. Obtain preliminary estimates of clinical activity as measured by the complete remission (complete response \[CR\], complete response with incomplete hematologic recovery \[CRi\], or complete response with partial hematologic recovery \[CRh\]) rate and minimal residual disease (MRD) rate. II. Obtain preliminary estimates of clinical activity as measured by overall response rate (CR, CRi, CRh, morphologic leukemia free state \[MLFS\], and partial response \[PR\]). III. Obtain preliminary estimates of median time to complete remission. IV. Obtain preliminary estimates of median time to first response. V. Obtain preliminary estimates of response duration in all participants and in those attaining CR/CRi/CRh. VI. Obtain preliminary estimates of median and 1-year event-free survival (EFS). VII. Obtain preliminary estimates of median and 1-year overall survival (OS). EXPLORATORY OBJECTIVES: I. Characterize the effects of the combination on cellular differentiation of leukemic cells as measured by flow cytometry performed at study entry and at serial timepoints throughout the study. II. Evaluate changes in promotor methylation patterns after treatment with combination therapy. III. Evaluate changes in gene expression of RAS pathway regulators as a result of the combination therapy. OUTLINE: This is dose-escalation study of cobimetinib followed by a dose-expansion study. Patients receive cobimetinib orally (PO) once daily (QD) on days 1-21 and enasidenib mesylate PO QD on days 1-28 of each cycle. Treatment repeats every 28 days for 12 cycles in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up at 30 days, and every 3 months for 1 year at last treatment dose.

Conditions

• Recurrent Acute Myeloid Leukemia
• Refractory Acute Myeloid Leukemia

Interventions

Type	Name	Description
DRUG	Cobimetinib	Given PO
DRUG	Enasidenib Mesylate	Given PO

Timeline

• Start date: 2022-11-03
• Primary completion: 2027-05-03
• Completion: 2027-05-03
• First posted: 2022-07-01
• Last updated: 2025-09-16

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study