FDA Approves Inluriyo-Verzenio Combination for ESR1-Mutated Breast Cancer

The Food and Drug Administration approved imlunestrant, sold as Inluriyo, in combination with abemaciclib, sold as Verzenio, on September 18, 2026. Eli Lilly makes both drugs. The combination is now approved for adults with estrogen receptor-positive, HER2-negative, ESR1-mutated advanced or metastatic breast cancer whose disease progressed after at least one prior line of endocrine therapy, according to the FDA.

How a single gene mutation outlasts hormone therapy

About 70 percent of breast cancers are estrogen receptor-positive, meaning estrogen drives their growth, and the standard first response is a hormone-blocking drug. In a meaningful share of patients, the tumor's ESR1 gene later mutates in a way that keeps the estrogen receptor switched on even while the original hormone drug is still in the blood. Research published in JNCI Cancer Spectrum found ESR1 mutations in roughly 1 percent of untreated tumors, rising to as high as 40 percent among women with metastatic ER-positive, HER2-negative breast cancer who have already gone through one or more lines of hormone therapy. That gap between rare and common is what imlunestrant was built to close: it is designed to degrade the estrogen receptor even after an ESR1 mutation has changed its shape.

The trial behind the approval

The approval rests on EMBER-3, a randomized, open-label Phase 3 trial (NCT04975308) that enrolled 874 patients and compared the imlunestrant-abemaciclib combination against imlunestrant alone and against an endocrine therapy chosen by each patient's physician. Among the 159 patients whose tumors carried an ESR1 mutation, the combination produced an objective response in 35 percent of patients, compared with 15 percent on imlunestrant alone. The FDA also cleared Guardant360 CDx, a blood test that detects ESR1 mutations from a tumor's circulating DNA, as the companion diagnostic required to identify who qualifies for the combination.

Dr. Komal Jhaveri of Memorial Sloan Kettering Cancer Center described the treatment gap the approval targets, in comments reported by Healio.

“We have an urgent need for effective and safe treatment options for patients with disease progression on adjuvant or first-line therapy.”

What the approval does not settle

EMBER-3 was open-label, meaning patients and doctors knew which drugs they were receiving, which can shape how symptoms get reported even though a scan measurement like tumor size is harder to skew. Progression-free survival, not overall survival, is the endpoint behind this approval, so it is not yet established whether the combination helps patients live longer rather than only keeping the cancer controlled on scans for longer. Imlunestrant alone already carried its own FDA approval for the same ESR1-mutated population in 2025, so this decision adds a second combination option rather than creating the first available treatment for the mutation.

• Abemaciclib carries FDA warnings for diarrhea, low white blood cell counts (neutropenia), interstitial lung disease, liver toxicity, and blood clots (venous thromboembolism).
• Both drugs carry an embryo-fetal toxicity warning and are not recommended during pregnancy.
• The approval applies only to patients confirmed to carry an ESR1 mutation by the Guardant360 CDx test, not to ER-positive breast cancer generally.