Phase II Trial of MEK Inhibitor Binimetinib (MEK162) in RAS-mutant Acute Myeloid Leukemia

Area of Science:

• Hematology
• Oncology
• Pharmacology

Background:

• Relapsed and refractory (R/R) acute myeloid leukemia (AML) presents significant therapeutic challenges with poor patient outcomes.
• Dysregulation of the mitogen-activated protein (MAP) kinase/extracellular-signal regulated kinase (ERK) pathway is common in AML and myelodysplastic syndrome (MDS).
• Preclinical data and early trials indicate potential efficacy of MAP-ERK kinase (MEK) inhibition in AML treatment.

Purpose of the Study:

• To evaluate the safety and efficacy of the MEK 1/2 inhibitor binimetinib in patients with advanced myeloid malignancies.
• To assess the tolerability and preliminary response of binimetinib in a phase II study.

Main Methods:

• A phase II study enrolled 19 patients with R/R AML and MDS ineligible for intensive chemotherapy or resistant/intolerant to standard treatments.
• Patients received binimetinib 45 mg twice daily continuously in 28-day cycles.
• Safety, adverse events, and response rates were assessed.

Main Results:

• The study cohort had a median age of 64 years, with a median of 3 prior therapies and 49% bone marrow blasts.
• Fourteen patients (74%) had RAS mutations.
• The most frequent grade 3/4 adverse events included hypokalemia, hypotension, lung infection, and febrile neutropenia. One of 13 evaluable patients (8%) achieved a complete response with incomplete blood count recovery.

Conclusions:

• Binimetinib demonstrated a tolerable safety profile in advanced myeloid malignancies, including RAS-mutant AML.
• The observed response rate was minimal, highlighting the need for refined patient selection strategies.
• Future research should explore synergistic combination therapies incorporating MEK inhibition.