AUGMENT-101
A study of revumenib in relapsed or refractory leukemias including those with an MLL/KMT2A gene rearrangement or NPM1 mutation
Phase 1/2NCT04065399
- Population
- Relapsed or refractory acute leukemia with a KMT2A rearrangement, or relapsed or refractory AML with an NPM1 mutation
- Design
- Phase 1/2, open-label, dose-escalation and expansion study of revumenib (the phase 2 portion at 163 mg every 12 hours with a strong cytochrome P450 inhibitor, in 28-day cycles). Single-arm; no randomized comparator. Primary end points of the phase 2 portion: CR + CRh rate and safety.
- Arms
- Revumenib (experimental): Revumenib orally every 12 hours in 28-day cycles
- People
- Issa GC
Show the numbers
| Endpoint | Analysis | Revumenib | Control | Effect |
|---|---|---|---|---|
| CR+CRhPhase 1 efficacy analysis population (KMT2A-rearranged or NPM1-mutant relapsed or refractory acute leukaemia; 18 of 60 evaluable patients achieved CR/CRh)Complete remission or complete remission with partial haematologic recovery | primaryIssa 2023 | 30% (18.8–43.2%) | — | — |
| CR+CRhEfficacy-evaluable patients with centrally confirmed KMT2A rearrangement (n = 57 of 94 treated)Complete remission or complete remission with partial hematologic recovery | primaryIssa 2025 | 22.8% (12.7–35.8%) | — | P=.0036Prespecified interim analysis; the P value tests against a null hypothesis of 10% (one-sided P = .0036 in the full text). |
| ORREfficacy-evaluable patients with centrally confirmed KMT2A rearrangement (n = 57 of 94 treated)Overall response rate in relapsed or refractory acute leukemia; response criteria are not given in the abstract | primaryIssa 2025 | 63.2% (49.3–75.6%) | — | 15 of 22 patients (68.2%) had no detectable residual disease, as stated in the abstract. Secondary end point (the primary end points were CR + CRh rate and safety). |
| CR+CRhProtocol-defined efficacy-evaluable adults with relapsed or refractory NPM1-mutated AML (n = 64 of 84 treated)Complete remission or complete remission with partial hematologic recovery | primaryArellano 2025 | 23.4% (13.8–35.7%) | — | P=.0014 (1-sided)Overall response rate 46.9%; median duration of CR + CRh 4.7 months; 75.0% had received venetoclax; data as of 18 September 2024. The 1-sided P value tests against a null hypothesis of a 10% CR + CRh rate. |
| Endpoint | Analysis | Revumenib | Control | Effect |
|---|---|---|---|---|
| CR+CRhPhase 1 efficacy analysis population (KMT2A-rearranged or NPM1-mutant relapsed or refractory acute leukaemia; 18 of 60 evaluable patients achieved CR/CRh)Complete remission or complete remission with partial haematologic recovery | primaryIssa 2023 | 30% (18.8–43.2%) | — | — |
| CR+CRhEfficacy-evaluable patients with centrally confirmed KMT2A rearrangement (n = 57 of 94 treated)Complete remission or complete remission with partial hematologic recovery | primaryIssa 2025 | 22.8% (12.7–35.8%) | — | P=.0036Prespecified interim analysis; the P value tests against a null hypothesis of 10% (one-sided P = .0036 in the full text). |
| ORREfficacy-evaluable patients with centrally confirmed KMT2A rearrangement (n = 57 of 94 treated)Overall response rate in relapsed or refractory acute leukemia; response criteria are not given in the abstract | primaryIssa 2025 | 63.2% (49.3–75.6%) | — | 15 of 22 patients (68.2%) had no detectable residual disease, as stated in the abstract. Secondary end point (the primary end points were CR + CRh rate and safety). |
| CR+CRhProtocol-defined efficacy-evaluable adults with relapsed or refractory NPM1-mutated AML (n = 64 of 84 treated)Complete remission or complete remission with partial hematologic recovery | primaryArellano 2025 | 23.4% (13.8–35.7%) | — | P=.0014 (1-sided)Overall response rate 46.9%; median duration of CR + CRh 4.7 months; 75.0% had received venetoclax; data as of 18 September 2024. The 1-sided P value tests against a null hypothesis of a 10% CR + CRh rate. |
Appears in
Sources
Issa GC, Aldoss I, DiPersio J, Cuglievan B, Stone R, Arellano M, et al. The menin inhibitor revumenib in KMT2A-rearranged or NPM1-mutant leukaemia. Nature. 2023;615(7954):920-924.
Issa GC, Aldoss I, Thirman MJ, DiPersio J, Arellano M, Blachly JS, et al. Menin Inhibition With Revumenib for KMT2A-Rearranged Relapsed or Refractory Acute Leukemia (AUGMENT-101). J Clin Oncol. 2025;43(1):75-84.
Arellano ML, Thirman MJ, DiPersio JF, Heiblig M, Stein EM, Schuh AC, et al. Menin inhibition with revumenib for NPM1-mutated relapsed or refractory acute myeloid leukemia: the AUGMENT-101 study. Blood. 2025;146(9):1065-1077.