Multinational phase 1-2 trial of revumenib for KMT2A-rearranged relapsed/refractory acute leukemia: phase 2 results

Revumenib is a small molecule inhibitor of het menin-KMT2A interaction. The multinational phase 1-2 AUGMENT-101 trial evaluated revumenib for patients with relapsed or refractory (R/R) acute leukemia with KMT2A rearrangement. Grade ≥3 adverse events included febrile neutropenia (37.2% of patients), differentiation syndrome (16.0%), and QTc prolongation (13.8%). The complete response (CR) and CR plus partial hematogic recovery rate was 22.8% (95% CI 12.7-35.8), exceeding the null hypothesis of 10% (p=0.0036). Overall response rate was 63.2% (95% CI 49.3-75.6), with 68% having no detectable residual disease. Median durations of response and overall survival were 6.4 months (95% CI 3.4-NR) and 8.0 months (4.1-NR), respectively. The authors conclude that revumenib led to high remission rates with a predictable safety profile in R/R acute leukemia with KMT2A rearrangement.