{"entity":{"id":"ember-3","kind":"trial","name":"EMBER-3","aka":[],"tldr":"An oral SERD that works alone in ESR1-mutant tumours and, combined with abemaciclib, doubles progression-free time in everyone regardless of mutation.","summary":"Three arms (imlunestrant n=331; standard ET n=330; imlunestrant + abemaciclib n=213). In ESR1-mutant tumours imlunestrant alone: PFS 5.5 vs 3.8 months (HR 0.62). Imlunestrant + abemaciclib vs imlunestrant: PFS 9.4 vs 5.5 months (HR 0.57; updated 10.9 vs 5.5, HR 0.59), with benefit irrespective of ESR1 status. Updated analysis (SABCS 2025): ESR1-mutant OS 34.5 vs 23.1 months for monotherapy vs standard ET. FDA approved imlunestrant (Inluriyo) 25 September 2025 for ESR1-mutant disease.","status":"positive","asOf":"2026-09-07","links":[{"label":"ClinicalTrials.gov NCT04975308","url":"https://clinicaltrials.gov/study/NCT04975308"},{"label":"Lilly approval release","url":"https://investor.lilly.com/news-releases/news-release-details/us-fda-approves-inluriyo-imlunestrant-adults-er-her2-esr1"}],"tags":[],"related":[],"cancers":["breast-hr-positive","hr-positive-metastatic-post-cdk46"],"sections":[],"technologies":["endocrine-therapy"],"targets":["estrogen-receptor","cdk4-6"],"drugs":["imlunestrant","abemaciclib"],"companies":["eli-lilly"],"institutions":[],"pathways":[],"terms":["esr1-mutation","oral-serd"],"trials":[],"people":["komal-jhaveri"],"bottlenecks":[],"keyPapers":["paper-ember-3-n-engl-j-med-2025"],"journals":[],"dependsOn":[],"notes":[],"nct":"NCT04975308","phase":"3","setting":"ER+/HER2- advanced breast cancer after ≥1 endocrine line: imlunestrant vs standard endocrine therapy, and imlunestrant + abemaciclib vs imlunestrant","sponsor":"Eli Lilly","result":"PFS HR 0.62 (ESR1-mutant, monotherapy); HR 0.57 (combination vs monotherapy).","started":"2021-10-04","startedType":"actual","yearReported":2024,"enrolled":874,"enrolledBasis":"registry","outcomes":[{"endpoint":"Progression-free survival, ESR1-mutant (imlunestrant vs standard ET)","primary":true,"unit":"months","arms":[{"name":"Imlunestrant","value":5.5},{"name":"Standard endocrine therapy","value":3.8}],"hr":0.62,"ci":[0.46,0.82],"p":"<0.001","source":"https://www.nejm.org/doi/full/10.1056/NEJMoa2410858"},{"endpoint":"Progression-free survival (imlunestrant + abemaciclib vs imlunestrant)","primary":true,"unit":"months","arms":[{"name":"Imlunestrant + abemaciclib","n":213,"value":10.9},{"name":"Imlunestrant","n":213,"value":5.5}],"hr":0.59,"ci":[0.46,0.75],"p":"<0.001","source":"https://www.annalsofoncology.org/article/S0923-7534(25)06289-1/fulltext"},{"endpoint":"Overall survival, ESR1-mutant (imlunestrant vs standard ET), updated","unit":"months","arms":[{"name":"Imlunestrant","value":34.5},{"name":"Standard endocrine therapy","value":23.1}],"source":"https://www.mskcc.org/clinical-updates/sabcs-2025-news-updated-ember-3-efficacy-results-for-imlunestrant-with-or-without-abemaciclib-in-er-her2-advanced-breast"}],"replication":"Monotherapy effect consistent with EMERALD and VERITAC-2; the combination result is the first randomised evidence for oral SERD + CDK4/6 after prior CDK4/6 exposure."},"route":"/trials/ember-3/","neighbours":{"cancer":[{"id":"breast-hr-positive","kind":"cancer","name":"HR-positive / HER2-negative breast cancer","route":"/cancers/breast-hr-positive/"},{"id":"hr-positive-metastatic-post-cdk46","kind":"cancer","name":"HR-positive metastatic breast cancer after CDK4/6 inhibitors","route":"/cancers/hr-positive-metastatic-post-cdk46/"}],"technology":[{"id":"endocrine-therapy","kind":"technology","name":"Endocrine therapy (SERMs, AIs, SERDs)","route":"/technologies/endocrine-therapy/"}],"target":[{"id":"cdk4-6","kind":"target","name":"CDK4/6","route":"/targets/cdk4-6/"},{"id":"estrogen-receptor","kind":"target","name":"Estrogen receptor (ERα)","route":"/targets/estrogen-receptor/"}],"drug":[{"id":"abemaciclib","kind":"drug","name":"Abemaciclib","route":"/drugs/abemaciclib/"},{"id":"imlunestrant","kind":"drug","name":"Imlunestrant","route":"/drugs/imlunestrant/"}],"company":[{"id":"eli-lilly","kind":"company","name":"Eli Lilly (incl. Loxo)","route":"/companies/eli-lilly/"}],"term":[{"id":"esr1-mutation","kind":"term","name":"ESR1 mutation","route":"/terms/esr1-mutation/"},{"id":"oral-serd","kind":"term","name":"Oral SERD","route":"/terms/oral-serd/"}],"person":[{"id":"komal-jhaveri","kind":"person","name":"Komal Jhaveri","route":"/people/komal-jhaveri/"}],"paper":[{"id":"paper-ember-3-n-engl-j-med-2025","kind":"paper","name":"Imlunestrant with or without Abemaciclib in Advanced Breast Cancer","route":"/key-papers/paper-ember-3-n-engl-j-med-2025/"}],"pairing":[{"id":"oral-serd-plus-cdk46-after-esr1","kind":"pairing","name":"Oral SERD + CDK4/6 inhibitor after ESR1 emergence","route":"/pairings/oral-serd-plus-cdk46-after-esr1/"}],"roadmap":[{"id":"hormonal-therapy-roadmap","kind":"roadmap","name":"Hormonal therapy roadmap: removing the ovaries → tamoxifen → oral degraders switched by a blood test","route":"/roadmaps/hormonal-therapy-roadmap/"}]}}