{"entity":{"id":"paper-augment-101-revumenib-menin-nature-2023","kind":"paper","name":"AUGMENT-101: revumenib, the first menin inhibitor, in relapsed leukaemias driven by KMT2A rearrangement or NPM1 mutation","aka":[],"tldr":"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.","asOf":"2026-09-08","links":[{"label":"PubMed search","url":"https://pubmed.ncbi.nlm.nih.gov/?term=AUGMENT-101%20revumenib%20menin%20inhibitor%20KMT2A%20NPM1%20Issa%20Nature%202023"},{"label":"ClinicalTrials.gov NCT04065399","url":"https://clinicaltrials.gov/study/NCT04065399"}],"tags":[],"related":["menin-plus-venetoclax-hma"],"cancers":["aml","all-leukemia"],"sections":[],"technologies":[],"targets":["menin","kmt2a","npm1"],"drugs":["revumenib","ziftomenib"],"companies":["syndax","kura-oncology"],"institutions":["md-anderson"],"pathways":[],"terms":["mrd-negative-cr","orr"],"trials":["augment-101"],"people":[],"bottlenecks":["b-undruggable-targets","b-resistance"],"keyPapers":[],"journals":["nature"],"dependsOn":[],"notes":[],"journal":"Nature","year":2023,"doi":"10.1038/s41586-023-05812-3","pmid":"36922593","authors":"Issa GC, Aldoss I, DiPersio J, et al.","paperType":"translational","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."],"whatItMeans":"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."],"changedPractice":true,"participants":68},"route":"/key-papers/paper-augment-101-revumenib-menin-nature-2023/","neighbours":{"pairing":[{"id":"menin-plus-venetoclax-hma","kind":"pairing","name":"Menin inhibitor + venetoclax + azacitidine","route":"/pairings/menin-plus-venetoclax-hma/"}],"cancer":[{"id":"all-leukemia","kind":"cancer","name":"Acute lymphoblastic leukaemia","route":"/cancers/all-leukemia/"},{"id":"aml","kind":"cancer","name":"Acute myeloid leukaemia","route":"/cancers/aml/"},{"id":"all-infant","kind":"cancer","name":"Infant acute lymphoblastic leukaemia (KMT2A-rearranged, under one year)","route":"/cancers/all-infant/"},{"id":"aml-npm1-kmt2a","kind":"cancer","name":"NPM1-mutated and KMT2A-rearranged acute myeloid leukaemia","route":"/cancers/aml-npm1-kmt2a/"}],"target":[{"id":"kmt2a","kind":"target","name":"KMT2A (MLL) rearrangement","route":"/targets/kmt2a/"},{"id":"menin","kind":"target","name":"Menin","route":"/targets/menin/"},{"id":"npm1","kind":"target","name":"NPM1 mutation","route":"/targets/npm1/"}],"drug":[{"id":"revumenib","kind":"drug","name":"Revumenib","route":"/drugs/revumenib/"},{"id":"ziftomenib","kind":"drug","name":"Ziftomenib","route":"/drugs/ziftomenib/"}],"company":[{"id":"kura-oncology","kind":"company","name":"Kura Oncology","route":"/companies/kura-oncology/"},{"id":"syndax","kind":"company","name":"Syndax Pharmaceuticals","route":"/companies/syndax/"}],"institution":[{"id":"md-anderson","kind":"institution","name":"MD Anderson Cancer Center","route":"/institutions/md-anderson/"}],"term":[{"id":"mrd-negative-cr","kind":"term","name":"MRD-negative complete remission","route":"/terms/mrd-negative-cr/"},{"id":"orr","kind":"term","name":"Objective response rate (ORR)","route":"/terms/orr/"}],"trial":[{"id":"augment-101","kind":"trial","name":"AUGMENT-101","route":"/trials/augment-101/"}],"bottleneck":[{"id":"b-resistance","kind":"bottleneck","name":"Acquired resistance to every therapy","route":"/bottlenecks/b-resistance/"},{"id":"b-undruggable-targets","kind":"bottleneck","name":"The undruggable drivers","route":"/bottlenecks/b-undruggable-targets/"}],"journal":[{"id":"nature","kind":"journal","name":"Nature","route":"/journals/nature/"}],"person":[{"id":"eytan-stein","kind":"person","name":"Eytan M. Stein","route":"/people/eytan-stein/"},{"id":"ghayas-issa","kind":"person","name":"Ghayas C. Issa","route":"/people/ghayas-issa/"}],"roadmap":[{"id":"epigenetics-roadmap","kind":"roadmap","name":"Epigenetic therapy roadmap: loosening silenced genes → mutation-specific enzymes → editing the epigenome","route":"/roadmaps/epigenetics-roadmap/"}]}}