AUGMENT‑101 Overview
Study Design: Phase 1/2, open-label study (ClinicalTrials.gov: NCT04065399), evaluating safety and efficacy of oral revumenib in relapsed/refractory (R/R) acute leukemia with KMT2Ar or NPM1 mutations .
Phase I (Initial Dose-Escalation Cohort)
Population: R/R KMT2Ar or NPM1-mutant acute leukemia. Efficacy: Overall Response Rate (ORR): 53% (32/60). CR/CRh: 30% (18/60); of those, 78% were MRD-negative . Time to response: ~1.9 months; median CR/CRh duration: 9.1 months. 38% of responders proceeded to transplant .
Phase II – KMT2Ar Cohort (Pivotal)
Efficacy: CR/CRh rate ~23% (13/57; p = 0.0036), exceeding the null hypothesis of 10% . ORR: 63% – significant blast clearance allowed some patients to go to transplant even without full CR/CRh . Median duration of CR/CRh: 6.4 months, with ~46% still in response at cutoff . Time to response: ~1.9 months . MRD negativity: ~70% of CR/CRh responders were MRD-negative . Median overall survival: 8.0 months . Safety: Managed well with low discontinuation (only 6%), none due to differentiation syndrome or QTc prolongation . Consistency: Primary endpoint met across age groups, AML vs ALL, and other subgroups .
Phase II – mNPM1 AML Cohort
Efficacy: CR/CRh rate ~23% (15/64; p = 0.0014); ORR 47% (30/64) in heavily pretreated patients, including those with prior venetoclax exposure . Median duration of CR/CRh: 4.7 months, with three patients still responding at the data cutoff . MRD negativity among CR/CRh responders: ~64% . 16–17% proceeded to HSCT; some restarted revumenib post-transplant . Impact: Data support an sNDA submission planned for H1 2025, following expected FDA approval in Q4 2024 for KMT2Ar indication .
Key Insights & Implications
Targeted Therapy Breakthrough: Revumenib demonstrates meaningful activity in molecularly defined, often high‑risk subtypes of acute leukemia with otherwise limited options . MRD‑Negative Remissions & Transplant Enablement: Robust MRD negativity rates and the ability to bridge patients to potentially curative HSCT are particularly promising. Favorable Safety Profile: Manageable adverse events, with low discontinuation due to toxicities such as differentiation syndrome or QTc prolongation . Regulatory Momentum: FDA Breakthrough Therapy designation secured; NDA submitted for KMT2Ar, and mNPM1 sNDA in progress