FDA
Inluriyo OK’d for ER+, HER2-, ESR1-mutated metastatic breast cancer
Brand name: Inluriyo
Generic name: imlunestrant
Manufacturer: Eli Lilly
Approval date: September 25, 2025
FDA has approved Inluriyo (imlunestrant), an estrogen receptor antagonist, for adults with estrogen receptor (ER)-positive, human epidermal growth factor 2 (HER2)-negative, estrogen receptor-1 (ESR1)-mutated advanced or metastatic breast cancer with disease progression following at least one line of endocrine therapy.
The agency also approved the Guardant360 CDx assay as a companion diagnostic device to identify patients with breast cancer with ESR1 mutations for treatment with imlunestrant.
Efficacy
Efficacy was evaluated in EMBER-3 (NCT04975308), a randomized, open-label, active-controlled, multicenter trial that enrolled 874 patients with ER-positive, HER2-negative locally advanced or metastatic breast cancer previously treated with an aromatase inhibitor either alone or in combination with a CDK4/6 inhibitor. Patients were excluded if they were eligible to receive a PARP inhibitor.
Patients were randomized 1:1:1 to imlunestrant, an investigator’s choice of endocrine therapy (fulvestrant or exemestane), or an additional investigational combination regimen. Randomization was stratified by previous treatment with a CDK4/6 inhibitor, presence of visceral metastasis, and geographic region. ESR1 mutational status was determined by blood circulating tumor deoxyribonucleic acid (ctDNA) analysis using the Guardant360 CDx assay and was limited to specific ESR1 mutations in the ligand-binding domain.
The major efficacy outcome was investigator-assessed progression-free survival (PFS) comparing imlunestrant to the investigator’s choice of endocrine therapy in patients with ESR1 mutated tumors. Other efficacy outcome measures included overall survival (OS) and objective response rate (ORR). In the ESR1 mutated population (n=256), a statistically significant difference in investigator-assessed PFS for imlunestrant compared with investigator’s choice of endocrine therapy was observed. Median PFS was 5.5 months (95% confidence interval [CI], 3.9, 7.4) in the imlunestrant arm and 3.8 months (95% CI, 3.7, 5.5) in the investigator's choice arm (hazard ratio, 0.62; 95% CI, 0.46, 0.82; p-value 0.0008). The ORR was 14.3% in the imlunestrant arm and 7.7% in the investigator's choice arm. At the time of the PFS analysis, OS data was immature with 31% of deaths in the ESR1 mutated population.
Safety
The most common adverse events (≥10%), including lab abnormalities were decreased hemoglobin, musculoskeletal pain, decreased calcium, decreased neutrophils, increased AST and ALT, fatigue, diarrhea, increased triglycerides, nausea, decreased platelets, constipation, increased cholesterol, and abdominal pain.
Recommended dose
The recommended dosage of Inluriyo is 400 mg orally once daily (on an empty stomach at least 2 hours before food, or 1 hour after food) until disease progression or unacceptable toxicity.
Sources:
FDA approves imlunestrant for ER-positive, HER2-negative, ESR1-mutated advanced or metastatic breast cancer. [News release]. 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-imlunestrant-er-positive-her2-negative-esr1-mutated-advanced-or-metastatic-breast
Inluriyo (imlunestrant) [package insert]. Food and Drug Administration. https://www.accessdata.fda.gov/drugsatfda_docs/label/2025/218881s000lbl.pdf Revised September 2025. Accessed September 29, 2025.
US FDA approves Inluriyo (imlunestrant) for adults with ER+, HER2-, ESR1-mutated advanced or metastatic breast cancer. [News release]. 2025. https://investor.lilly.com/news-releases/news-release-details/us-fda-approves-inluriyo-imlunestrant-adults-er-her2-esr1