A Phase 2 clinical trial has been launched by Break Through Cancer to investigate the efficacy of combining revumenib and venetoclax in eliminating minimal residual disease (MRD) in patients with acute myeloid leukemia (AML). The trial (NCT06284486) is designed to assess whether this dual inhibition strategy can lead to improved progression-free survival in AML patients who often relapse due to residual cancer cells.
Targeting Minimal Residual Disease in AML
AML, a cancer with a five-year survival rate of approximately 30% in adults, frequently relapses even after initial treatment success. This relapse is often attributed to the persistence of MRD, which refers to the small number of cancer cells that remain after treatment. The Eradicating Minimal Residual Disease in AML TeamLab at Break Through Cancer aims to address this critical issue by developing strategies to target and eliminate these residual cells.
Revumenib and Venetoclax: A Synergistic Approach
The trial will evaluate the safety and tolerability of revumenib, an investigational small molecule drug developed by Syndax Pharmaceuticals, in combination with venetoclax, an approved drug by AbbVie. Revumenib targets menin, a protein involved in cancer progression in AML patients with specific mutations such as NPM1, NUP98, or KMT2A. Venetoclax inhibits BCL2, a protein that prevents cancer cells from undergoing apoptosis (cell death).
Ghayas Issa, MD, from The University of Texas MD Anderson Cancer Center, a TeamLab member, stated, "We’re hoping by targeting MRD that we’re going to prevent relapse in these patients, and hopefully, they will have longer remissions without leukemia."
Trial Design and Objectives
The multi-site trial will enroll patients across Break Through Cancer clinical sites, with MD Anderson being the first to enroll. The primary endpoint is MRD clearance, and researchers will assess whether achieving MRD negativity correlates with longer progression-free survival. Additionally, the study will analyze patient samples to identify biomarkers that predict drug response, improve MRD measurement techniques, and determine optimal MRD sampling times.
Jacqueline Garcia, MD, from Dana-Farber Cancer Institute and a TeamLab member, explained, "If we can more deeply clear the leukemia, we will be more likely to get rid of residual cells that have additional mutations present."
Implications for AML Treatment
This research has the potential to significantly impact how AML is treated by providing insights into targeting residual cancer cells before the cancer progresses. Early intervention based on improved MRD detection and targeted therapies could potentially lead to cures for AML.
