FDA approves imlunestrant in combination with abemaciclib for ER-positive, HER2-negative, ESR1-mutated advanced or metastatic breast cancer
Regulatory approval: On Sept 18, 2026, the FDA approved imlunestrant (Inluriyo) plus abemaciclib (Verzenio) for adults with ER-positive, HER2-negative, ESR1-mutated advanced or metastatic breast cancer (FDA-authorized test required) after progression on at least one line of endocrine therapy. The companion diagnostic Guardant360 CDx was also approved. Approval was supported by EMBER-3, where benefit was reported as concentrated in the ESR1-mutated population; OS data were immature at interim analysis.
FDA approval (Sept 18, 2026)
The FDA approved imlunestrant (Inluriyo) in combination with abemaciclib (Verzenio) for adults with ER-positive, HER2-negative, ESR1-mutated advanced or metastatic breast cancer, as detected by an FDA-authorized test, with disease progression following at least one line of endocrine therapy. Inluriyo and Verzenio are manufactured by Eli Lilly and Company.
The FDA also approved Guardant360 CDx as a companion diagnostic to identify ESR1 mutations for treatment with imlunestrant plus abemaciclib.
Evidence base
Efficacy was evaluated in EMBER-3 (NCT04975308), a randomized, open-label, active-controlled, multicenter trial (n=874) in ER-positive/HER2-negative locally advanced or metastatic breast cancer previously treated with an aromatase inhibitor (alone or with a CDK4/6 inhibitor). Patients eligible for a PARP inhibitor were excluded. Patients were randomized 1:1:1 to imlunestrant, investigator’s choice endocrine therapy (fulvestrant or exemestane), or imlunestrant + abemaciclib.
The major endpoint for the combination was investigator-assessed PFS (RECIST v1.1), comparing combination vs imlunestrant monotherapy. The overall-population PFS comparison was statistically significant, but FDA noted benefit was only observed in the ESR1-mutated population.
In an exploratory ESR1-mutated subgroup (n=159), PFS HR was 0.53 (95% CI, 0.35–0.80); median PFS was 11.1 vs 5.5 months (combination vs imlunestrant alone). ORR was 35% vs 15%. OS data were immature at interim analysis (35% deaths in ESR1-mutated patients).
Key safety and dosing highlights
Imlunestrant label: warning for embryo-fetal toxicity. Abemaciclib label: warnings for diarrhea, neutropenia, ILD/pneumonitis, hepatotoxicity, venous thromboembolism, and embryo-fetal toxicity.
Recommended doses: imlunestrant 400 mg PO once daily (empty stomach) plus abemaciclib 150 mg PO twice daily (with or without food) until progression or unacceptable toxicity.