Phase 2 revumenib menin inhibitor triplet with azacitidine + venetoclax in KMT2A-rearranged AML.

UNC Lineberger’s RAVEN study (NCT07605949) evaluates an all-oral/SC intensive-lower regimen combining revumenib (a menin–KMT2A/MLL interaction inhibitor that downregulates leukemogenic HOX/MEIS programs) with azacitidine (a DNA hypomethylating agent) and venetoclax (a BCL-2 inhibitor restoring apoptosis) as first-line therapy for newly diagnosed KMT2A-rearranged AML. The design includes an induction phase of up to three 28‑day cycles followed by continuation therapy until relapse, unacceptable toxicity, allogeneic stem cell transplant, or other discontinuation criteria, with an optional post-transplant revumenib maintenance component. The commercial angle is “targeted biology added to venetoclax/azacitidine,” leveraging the menin dependency of KMT2A-rearranged AML (a high-risk subset) to deepen remissions and potentially improve transplant readiness. Revumenib (Revuforj) is developed by Syndax Pharmaceuticals; azacitidine is widely marketed as Vidaza (Bristol Myers Squibb), and venetoclax is Venclexta (AbbVie/Genentech-Roche). Today’s typical care for older/unfit newly diagnosed AML is azacitidine + venetoclax; for fit patients it’s intensive induction (e.g., cytarabine/anthracycline) followed by consolidation and often transplant in high-risk genetics, so this study tests whether adding a KMT2A-pathway targeted agent can outperform existing backbones without adding prohibitive toxicity.