On Sept. 18, 2026, the Food and Drug Administration approved imlunestrant (Inluriyo) in combination with abemaciclib (Verzenio) for adults with estrogen receptor–positive, HER2-negative, ESR1-mutated advanced or metastatic breast cancer detected by an FDA-authorized test, after disease progression following at least one line of endocrine therapy, the agency and The ASCO Post (opens in new tab) both reported.
FDA also approved the Guardant360 CDx assay as a companion diagnostic to identify patients with ESR1 mutations for the combination. Both drugs are manufactured by Eli Lilly and Company.
Efficacy was evaluated in EMBER-3 (NCT04975308), a randomized, open-label, multicenter trial of 874 adults with ER-positive, HER2-negative locally advanced or metastatic breast cancer previously treated with an aromatase inhibitor alone or with a CDK4/6 inhibitor. Patients were randomized 1:1:1 to imlunestrant, investigator’s choice endocrine therapy (fulvestrant or exemestane), or imlunestrant plus abemaciclib.
In an exploratory subgroup of 159 patients with ESR1-mutated tumors, median progression-free survival was 11.1 months with the combination versus 5.5 months with imlunestrant alone (hazard ratio estimate 0.53; 95% CI 0.35–0.80). Objective response rates were 35% and 15%, respectively. Overall survival data were immature at interim analysis, with 35% of deaths among patients with ESR1-mutated tumors, FDA and ASCO Post said.
FDA noted that while the combination versus imlunestrant alone showed a statistically significant PFS comparison in the overall population, imlunestrant monotherapy did not demonstrate a PFS improvement versus investigator’s choice in the overall or ESR1 mutation–not-detected populations, indicating benefit was observed in the ESR1-mutant population. Recommended dosing is imlunestrant 400 mg orally once daily on an empty stomach and abemaciclib 150 mg orally twice daily until progression or unacceptable toxicity. Label warnings include embryo-fetal toxicity for imlunestrant and diarrhea, neutropenia, interstitial lung disease/pneumonitis, hepatotoxicity, venous thromboembolism, and embryo-fetal toxicity for abemaciclib.