# AUGMENT-101: revumenib, the first menin inhibitor, in relapsed leukaemias driven by KMT2A rearrangement or NPM1 mutation

Source: https://onco.cc/key-papers/paper-augment-101-revumenib-menin-nature-2023/  
OnCo record `paper-augment-101-revumenib-menin-nature-2023` (Key paper). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

Blocking menin, a scaffold protein the leukaemia depends on, produced remissions in heavily pretreated patients with KMT2A-rearranged or NPM1-mutated acute leukaemia.

## Summary

The phase 1 portion of AUGMENT-101 treated 68 adults and children with relapsed or refractory acute leukaemia carrying a KMT2A rearrangement or NPM1 mutation with oral revumenib (SNDX-5613), a small molecule that disrupts the menin-KMT2A interaction. Among 60 efficacy-evaluable patients the overall response rate was 53% and the rate of complete remission or remission with partial haematological recovery 30%, with most responders MRD-negative. QT prolongation was dose limiting and differentiation syndrome occurred in 16%. Resistance through MEN1 mutations was subsequently described. The phase 2 KMT2A-rearranged cohort met its primary endpoint and revumenib was approved in 2024 for KMT2A-rearranged acute leukaemia and in 2025 for NPM1-mutated AML, the first drugs in a new class.

## Fields

- Kind: Key paper
- Last checked: 2026-09-08
- Journal: Nature
- Year: 2023
- DOI: 10.1038/s41586-023-05812-3
- Authors: Issa GC, Aldoss I, DiPersio J, et al.
- Findings: 68 patients treated (60 efficacy-evaluable) with relapsed/refractory KMT2A-rearranged or NPM1-mutated acute leukaemia.; Overall response 53%; CR/CRh 30%; most remissions MRD-negative.; Dose-limiting toxicity was QT prolongation; differentiation syndrome in 16%.; Responses in both KMT2A-rearranged and NPM1-mutated disease and in children and adults.; Phase 2 KMT2A-rearranged cohort: CR/CRh in roughly a fifth of patients, sufficient for regulatory approval; acquired MEN1 mutations identified as a resistance mechanism.
- What it means: Revumenib proved that a transcriptional dependency, rather than a kinase, can be drugged in leukaemia, opening treatment for two genetic subgroups that together cover roughly a third of AML plus most infant ALL. It is now approved and is being combined with venetoclax-azacitidine and intensive chemotherapy in front-line trials. Single-agent remissions are often short without transplant.
- Caveats: Single-arm phase 1/2 in end-stage patients; no randomised data yet.; Modest CR/CRh rates as monotherapy; benefit likely to come from combinations and as a bridge to transplant.; QT prolongation and drug interactions with azoles require dose adjustment.; Resistance via MEN1 mutations emerges within months in some patients.

## Sources

- PubMed search: https://pubmed.ncbi.nlm.nih.gov/?term=AUGMENT-101%20revumenib%20menin%20inhibitor%20KMT2A%20NPM1%20Issa%20Nature%202023
- ClinicalTrials.gov NCT04065399: https://clinicaltrials.gov/study/NCT04065399

## Connected records

- pairings: [Menin inhibitor + venetoclax + azacitidine](https://onco.cc/pairings/menin-plus-venetoclax-hma/)
- cancers: [Acute lymphoblastic leukaemia](https://onco.cc/cancers/all-leukemia/), [Acute myeloid leukaemia](https://onco.cc/cancers/aml/), [Infant acute lymphoblastic leukaemia (KMT2A-rearranged, under one year)](https://onco.cc/cancers/all-infant/), [NPM1-mutated and KMT2A-rearranged acute myeloid leukaemia](https://onco.cc/cancers/aml-npm1-kmt2a/)
- targets: [KMT2A (MLL) rearrangement](https://onco.cc/targets/kmt2a/), [Menin](https://onco.cc/targets/menin/), [NPM1 mutation](https://onco.cc/targets/npm1/)
- drugs: [Revumenib](https://onco.cc/drugs/revumenib/), [Ziftomenib](https://onco.cc/drugs/ziftomenib/)
- companies: [Kura Oncology](https://onco.cc/companies/kura-oncology/), [Syndax Pharmaceuticals](https://onco.cc/companies/syndax/)
- institutions: [MD Anderson Cancer Center](https://onco.cc/institutions/md-anderson/)
- terms: [MRD-negative complete remission](https://onco.cc/terms/mrd-negative-cr/), [Objective response rate (ORR)](https://onco.cc/terms/orr/)
- trials: [AUGMENT-101](https://onco.cc/trials/augment-101/)
- bottlenecks: [Acquired resistance to every therapy](https://onco.cc/bottlenecks/b-resistance/), [The undruggable drivers](https://onco.cc/bottlenecks/b-undruggable-targets/)
- journals: [Nature](https://onco.cc/journals/nature/)
- people: [Eytan M. Stein](https://onco.cc/people/eytan-stein/), [Ghayas C. Issa](https://onco.cc/people/ghayas-issa/)
- roadmaps: [Epigenetic therapy roadmap: loosening silenced genes → mutation-specific enzymes → editing the epigenome](https://onco.cc/roadmaps/epigenetics-roadmap/)

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