The U.S. Food and Drug Administration (FDA) has granted full approval to imlunestrant in combination with abemaciclib for adults with estrogen receptor-positive (ER+), HER2-negative, ESR1-mutated locally advanced or metastatic breast cancer whose disease has progressed following at least one line of endocrine therapy.
The approval, announced by Eli Lilly and Company on September 18, 2026, applies to patients whose ESR1 mutation is detected using an FDA-authorized test.
The decision represents the second FDA approval for imlunestrant in less than a year, following its September 2025 approval as monotherapy for adults with ER-positive, HER2-negative, ESR1-mutated advanced or metastatic breast cancer after progression on at least one line of endocrine therapy.
FDA Approves Imlunestrant (Inluriyo) for ESR1-Mutated Metastatic Breast Cancer
EMBER-3 Trial Supports the Approval
The new indication is supported by results from the Phase 3 EMBER-3 trial (NCT04975308), which evaluated imlunestrant alone, standard endocrine therapy, and imlunestrant plus abemaciclib in patients with ER-positive, HER2-negative locally advanced or metastatic breast cancer previously treated with an aromatase inhibitor, with or without a CDK4/6 inhibitor.
Results from the Phase 3 EMBER-3 trial were published in the New England Journal of Medicine, showing that imlunestrant plus abemaciclib significantly improved progression-free survival compared with imlunestrant alone.
There is also a newer updated efficacy analysis published in Annals of Oncology, which reported sustained PFS benefit with longer follow-up.
The analysis supporting the FDA approval included 159 patients with ESR1-mutated metastatic breast cancer. Among them, 92 received imlunestrant alone and 67 received imlunestrant plus abemaciclib.
The combination doubled median progression-free survival (PFS) compared with imlunestrant alone:
- Imlunestrant + abemaciclib: 11.1 months
- Imlunestrant alone: 5.5 months
- Hazard ratio: 0.53 (95% CI, 0.35–0.80)
The result translates into a 47% reduction in the risk of disease progression or death with the combination.
The findings highlight the potential of simultaneously targeting estrogen receptor signaling and CDK4/6-mediated cell-cycle activity in patients whose disease has developed resistance to previous endocrine therapy.
Komal Jhaveri, MD, FACP, FASCO, Associate Attending in Breast Medicine and Early Drug Development Services at Memorial Sloan Kettering Cancer Center and principal investigator of EMBER-3 and EMBER-4, said:
“There is an urgent need for effective and safe treatment options for patients whose disease progresses after adjuvant or first-line treatment.”
She added that targeting the estrogen receptor and CDK4/6 pathways together may offer another approach to overcoming treatment resistance in this setting.
Lilly: Approval Expands the Role of Imlunestrant
The approval expands the role of imlunestrant beyond monotherapy and provides an additional all-oral combination option for patients with ESR1-mutated ER-positive, HER2-negative advanced breast cancer following progression on endocrine therapy.
Jacob Van Naarden, Executive Vice President and President of Lilly Oncology, said:
“This approval expands the potential of imlunestrant when used in combination with abemaciclib following disease progression.”
About Imlunestrant and Abemaciclib
Imlunestrant is an oral estrogen receptor antagonist developed by Eli Lilly and Company. It binds to and inhibits the estrogen receptor, a key driver of tumor growth in ER-positive breast cancer, and retains activity against tumors harboring ESR1 mutations, which are associated with acquired resistance to endocrine therapy.
Imlunestrant is already approved in the United States as monotherapy for adults with ER-positive, HER2-negative, ESR1-mutated advanced or metastatic breast cancer following progression on at least one line of endocrine therapy.
Abemaciclib is an oral, selective inhibitor of cyclin-dependent kinases 4 and 6 (CDK4/6). By inhibiting CDK4 and CDK6, it blocks cell-cycle progression and can reduce the proliferation of cancer cells.
Abemaciclib is used across multiple settings in HR-positive, HER2-negative breast cancer, including certain patients with high-risk early breast cancer and patients with advanced or metastatic disease.
The combination of imlunestrant and abemaciclib is designed to simultaneously suppress estrogen receptor signaling and CDK4/6-mediated cell-cycle activity, addressing two pathways central to the growth and treatment resistance of ER-positive breast cancer.
Safety Profile
The safety profile of imlunestrant plus abemaciclib in EMBER-3 was generally consistent with the known profiles of the individual therapies, with most adverse events reported as Grade 1 or 2.
The most common adverse reactions and laboratory abnormalities occurring in at least 10% of patients included decreased neutrophils, diarrhea, decreased hemoglobin, decreased lymphocytes, nausea, decreased platelets, fatigue, infections, elevated AST and ALT, increased creatinine, vomiting, musculoskeletal pain, abdominal pain, decreased appetite, rash, cough, headache and decreased weight.
Permanent discontinuation due to adverse reactions occurred in 1% of patients for imlunestrant and 3.4% for abemaciclib in the combination arm.
The prescribing information includes warnings and precautions associated with abemaciclib, including severe diarrhea, neutropenia, interstitial lung disease/pneumonitis, hepatotoxicity, venous thromboembolism and embryo-fetal toxicity.
Expanding Treatment Options in ESR1-Mutated Breast Cancer
The approval provides another all-oral targeted treatment option for patients with ESR1-mutated ER-positive, HER2-negative advanced breast cancer following progression on endocrine therapy.
Imlunestrant is also being investigated in earlier-stage disease in the Phase 3 EMBER-4 trial (NCT05514054), evaluating adjuvant imlunestrant in patients with ER-positive, HER2-negative early breast cancer at increased risk of recurrence following standard endocrine therapy.
EMBER-4 has enrolled more than 8,000 patients across more than 650 sites in over 30 countries, with initial results anticipated in 2027.
Imlunestrant in combination with abemaciclib is now available in the United States.
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