{"entity":{"id":"ziftomenib","kind":"drug","name":"Ziftomenib","aka":[],"tldr":"Ziftomenib is the second menin inhibitor for leukaemia, approved in November 2025 as a once-daily pill for relapsed NPM1-mutated AML.","summary":"KOMET-001 (n=112 relapsed/refractory NPM1-mutated AML): CR 23%, ORR 33%, median OS 6.6 months. Approved 13 November 2025 (Kura Oncology / Kyowa Kirin). KOMET-007 combines ziftomenib with 7+3 and with venetoclax-azacitidine in newly diagnosed NPM1-mutated and KMT2A-rearranged AML, with high remission rates in early cohorts; KOMET-017 phase 3 registration studies are underway. Menin inhibition also being tested in KMT2Ar ALL.","status":"approved","asOf":"2026-09-07","links":[{"label":"FDA label (DailyMed)","url":"https://dailymed.nlm.nih.gov/dailymed/search.cfm?query=Ziftomenib"}],"tags":[],"related":["revumenib","npm1-mutation"],"cancers":["aml","all-leukemia","aml-npm1-kmt2a"],"sections":[],"technologies":["epigenetic-drugs"],"targets":["menin","npm1","kmt2a"],"drugs":[],"companies":["kura-oncology"],"institutions":[],"pathways":[],"terms":["differentiation-syndrome"],"trials":["komet-001","nct07007312","nct07623616"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"brand":"Komzifti","modality":"Small-molecule menin inhibitor","mechanism":"Displaces KMT2A/KMT2A-fusion complexes from menin, silencing HOXA9/MEIS1 and releasing the differentiation block in NPM1-mutant and KMT2A-rearranged blasts.","approvals":[{"region":"US","year":2025,"indication":"Relapsed/refractory NPM1-mutated AML with no satisfactory alternative"}],"mechanismSteps":["Menin scaffolds KMT2A (or its fusion) onto chromatin at HOX loci","Ziftomenib occupies the menin pocket and evicts the complex","HOXA9 and MEIS1 transcription falls within days","Blasts differentiate (differentiation syndrome risk) and the leukaemic clone shrinks","MEN1 resistance mutations at the binding site can emerge after months"],"dosing":{"route":"Oral","schedule":"600 mg once daily until progression","monitoring":"Differentiation syndrome (boxed warning), QT, counts","source":"https://dailymed.nlm.nih.gov/dailymed/search.cfm?query=Ziftomenib"},"toxicity":[{"event":"Differentiation syndrome","source":"https://ascopost.com/news/november-2025/fda-approves-ziftomenib-for-npm1-positive-aml/","note":"Boxed warning; mitigated by early steroids and hydroxyurea"},{"event":"Nausea, diarrhoea","note":"Common, mostly low grade"},{"event":"Cytopenias","note":"Common in relapsed AML"}],"access":[],"regulatoryEvents":[{"date":"2025-11-13","type":"approval","region":"US","note":"KOMET-001; priority review","source":"https://ascopost.com/news/november-2025/fda-approves-ziftomenib-for-npm1-positive-aml/"}]},"route":"/drugs/ziftomenib/","neighbours":{"drug":[{"id":"revumenib","kind":"drug","name":"Revumenib","route":"/drugs/revumenib/"}],"biomarker":[{"id":"npm1-mutation","kind":"biomarker","name":"NPM1 mutation","route":"/biomarkers/npm1-mutation/"}],"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":"aml-paediatric","kind":"cancer","name":"Acute myeloid leukaemia in children","route":"/cancers/aml-paediatric/"},{"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/"}],"technology":[{"id":"epigenetic-drugs","kind":"technology","name":"Epigenetic drugs (HDAC, DNMT, EZH2, IDH, menin, BET)","route":"/technologies/epigenetic-drugs/"},{"id":"menin-inhibitors","kind":"technology","name":"Menin inhibitors","route":"/technologies/menin-inhibitors/"}],"target":[{"id":"hoxa9","kind":"target","name":"HOXA9","route":"/targets/hoxa9/"},{"id":"kmt2a","kind":"target","name":"KMT2A (MLL) rearrangement","route":"/targets/kmt2a/"},{"id":"meis1","kind":"target","name":"MEIS1","route":"/targets/meis1/"},{"id":"menin","kind":"target","name":"Menin","route":"/targets/menin/"},{"id":"npm1","kind":"target","name":"NPM1 mutation","route":"/targets/npm1/"}],"company":[{"id":"kura-oncology","kind":"company","name":"Kura Oncology","route":"/companies/kura-oncology/"}],"term":[{"id":"differentiation-syndrome","kind":"term","name":"Differentiation syndrome","route":"/terms/differentiation-syndrome/"}],"trial":[{"id":"nct07623616","kind":"trial","name":"A Phase 2 Clinical Study of Ziftomenib in Patients With Relapsed or Refractory NPM1-Mutated Acute Myeloid Leukemia","route":"/trials/nct07623616/"},{"id":"komet-001","kind":"trial","name":"KOMET-001","route":"/trials/komet-001/"},{"id":"myelomatch","kind":"trial","name":"myeloMATCH","route":"/trials/myelomatch/"},{"id":"nct07007312","kind":"trial","name":"Studies to Assess Ziftomenib in Combination With Ven+Aza or 7+3 in Patients With Untreated NPM1-m or KMT2A-r AML","route":"/trials/nct07007312/"}],"pairing":[{"id":"menin-plus-venetoclax-hma","kind":"pairing","name":"Menin inhibitor + venetoclax + azacitidine","route":"/pairings/menin-plus-venetoclax-hma/"}],"idea":[{"id":"idea-menin-infant-all","kind":"idea","name":"Menin inhibitors for infant KMT2A-rearranged ALL","route":"/ideas/idea-menin-infant-all/"}],"pathway":[{"id":"epigenetic-reprogramming","kind":"pathway","name":"Epigenetic reprogramming","route":"/pathways/epigenetic-reprogramming/"},{"id":"menin-kmt2a","kind":"pathway","name":"Menin / KMT2A (HOXA9-MEIS1 axis)","route":"/pathways/menin-kmt2a/"},{"id":"transcription-addiction","kind":"pathway","name":"Transcriptional machinery & addiction","route":"/pathways/transcription-addiction/"}],"bottleneck":[{"id":"b-undruggable-targets","kind":"bottleneck","name":"The undruggable drivers","route":"/bottlenecks/b-undruggable-targets/"}],"paper":[{"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","route":"/key-papers/paper-augment-101-revumenib-menin-nature-2023/"}],"roadmap":[{"id":"epigenetics-roadmap","kind":"roadmap","name":"Epigenetic therapy roadmap: loosening silenced genes → mutation-specific enzymes → editing the epigenome","route":"/roadmaps/epigenetics-roadmap/"}]}}