On September 25, 2025, the U.S. Food and Drug Administration (FDA) approved Eli Lilly’s estrogen receptor antagonist Imlunestrant (Inluriyo) for the treatment of adult patients with ER-positive, HER2-negative, ESR1-mutated advanced or metastatic breast cancer whose disease has progressed after at least one line of endocrine therapy.
Companion Diagnostic Approval
The FDA also approved the Guardant360 CDx assay as a companion diagnostic to identify patients with ESR1 mutations eligible for Imlunestrant treatment.
Key Evidence: EMBER-3 Trial
The approval was based on the phase III EMBER-3 trial (NCT04975308), which enrolled 874 patients with ER-positive, HER2-negative breast cancer previously treated with an aromatase inhibitor, with or without a CDK4/6 inhibitor. Patients were randomized into three groups:
- Imlunestrant monotherapy
- Investigator’s choice of endocrine therapy (fulvestrant or exemestane)
- An additional investigational combination regimen
In the ESR1-mutated population (n=256), the primary endpoint of progression-free survival (PFS) showed significant benefit:
- Imlunestrant: median PFS 5.5 months (95% CI: 3.9–7.4)
- Investigator’s choice: median PFS 3.8 months (95% CI: 3.7–5.5)
- Hazard ratio: 0.62 (95% CI: 0.46–0.82), p=0.0008
The objective response rate (ORR) was 14.3% with Imlunestrant vs. 7.7% with investigator’s choice.
Dosage and Administration
The recommended dose is 400 mg orally once daily (on an empty stomach: at least 2 hours before food or 1 hour after food), continued until disease progression or unacceptable toxicity.
Safety Information
The most common adverse events (≥10%) included anemia, musculoskeletal pain, hypocalcemia, neutropenia, elevated AST/ALT, fatigue, diarrhea, nausea, thrombocytopenia, constipation, hypercholesterolemia, and abdominal pain.
Regulatory Pathway
Imlunestrant received Fast Track designation and was reviewed using the FDA’s Assessment Aid to facilitate expedited review.
Conclusion
The approval of Imlunestrant offers a new targeted therapy option for patients with ESR1-mutated advanced or metastatic breast cancer. Future studies and real-world evidence will clarify its long-term efficacy and safety profile.
This article was produced by the Morningglorysciences editorial team.
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