Lilly Says Updated EMBER-3 Data Show Imlunestrant-Abemaciclib Nearly Doubled Progression-Free Survival; Combination Submitted for U.S. Review

Eli Lilly and Company on December 12, 2025 released updated results from its Phase 3 EMBER-3 trial testing Inluriyo (imlunestrant), an oral estrogen receptor antagonist, both alone and combined with Verzenio (abemaciclib), in patients with estrogen receptor-positive, HER2-negative advanced or metastatic breast cancer whose disease had progressed on a prior aromatase inhibitor, with or without a CDK4/6 inhibitor. The data were published in Annals of Oncology and presented in a late-breaking oral session at the San Antonio Breast Cancer Symposium, according to a Lilly announcement carried by PRNewswire. The imlunestrant-abemaciclib combination itself is not approved in the United States; Lilly said it has submitted the combination data for U.S. regulatory review in ESR1-mutated metastatic breast cancer.

From Monotherapy Approval to a Combination Under Review

Inluriyo already carries FDA approval, granted September 25, 2025, for adults with ER-positive, HER2-negative, ESR1-mutated advanced or metastatic breast cancer whose disease progressed after at least one line of endocrine therapy, according to the FDA. That approval was paired with clearance of the Guardant360 CDx assay as a companion diagnostic to identify ESR1 mutations. Based on FDA-reported results from that approval trial, the imlunestrant monotherapy arm reached a median progression-free survival of 5.5 months versus 3.8 months for investigator's choice endocrine therapy (hazard ratio 0.62, 95% CI 0.46–0.82; p=0.0008) in the ESR1-mutated population of 256 patients. By our calculation, that is a difference of 1.7 months, or roughly a 44.7% relative improvement (5.5 minus 3.8, divided by 3.8, times 100), based on the FDA's reported figures for that specific comparison.

The newly disclosed combination data test imlunestrant alongside abemaciclib rather than against endocrine therapy alone. Interpretation, based on the approval and dosing facts above: because Inluriyo is dosed 400 mg once daily as two 200 mg tablets on an empty stomach and Verzenio is an oral tablet taken twice daily, per the FDA and Lilly labeling, an authorized combination would be an all-oral regimen that layers a CDK4/6 inhibitor onto an already-approved endocrine agent. It would not, on the evidence available, change the diagnostic-defined ESR1-mutated population identified by the Guardant360 CDx companion test. No FDA action date or approval timeline was disclosed in the available material.

What the Updated EMBER-3 Data Showed

According to Lilly's December 12 release, in all patients enrolled in EMBER-3, imlunestrant plus abemaciclib reduced the risk of progression or death by 41% compared with imlunestrant alone, with median progression-free survival of 10.9 months versus 5.5 months (hazard ratio 0.59, 95% CI 0.47–0.74; nominal p<0.0001). In the ESR1-mutated subgroup specifically, median progression-free survival for the combination reached 11.0 months versus 5.6 months for imlunestrant alone (hazard ratio 0.55, 95% CI 0.41–0.74; nominal p<0.001), Lilly reported.

Overall survival data remain immature. Lilly said the combination showed only a favorable trend versus imlunestrant alone (hazard ratio 0.82, 95% CI 0.59–1.16), with continued separation of the survival curves, and that follow-up for overall survival is ongoing. Median time to chemotherapy was numerically extended by more than a year with the combination, reaching 27.8 months versus 15.5 months for imlunestrant alone, per the company. Separately, as monotherapy in ESR1-mutated disease, imlunestrant showed an 11.4-month numeric improvement in median overall survival versus investigator's choice endocrine therapy, 34.5 months versus 23.1 months, though Lilly noted the statistical boundary for significance was not met.

Jacob Van Naarden, executive vice president and president of Lilly Oncology, said in the release: "Following the recent FDA approval of Inluriyo as monotherapy, these updated data demonstrate continued clinically meaningful benefit—both for patients receiving monotherapy and those receiving the combination with abemaciclib—and further reinforce its role in this treatment setting."

On tolerability, Lilly said safety across imlunestrant-based regimens was consistent with previous reports and that no new safety signals were observed with the additional follow-up. Per the labeling information in the release, serious adverse reactions occurred in 10% of patients who received Inluriyo and fatal adverse reactions in 1.8%. Adding abemaciclib brings that drug's established profile: across four clinical trials in 3,691 patients, diarrhea occurred in 81% to 90% of Verzenio patients, with Grade 3 diarrhea in 8% to 20%, and neutropenia in 37% to 46%.

Bottom line: the updated EMBER-3 readout, as reported by Lilly, strengthens the efficacy case for both imlunestrant monotherapy and the abemaciclib combination, but the combination is not approved in the United States and the company has only said it submitted the data for U.S. regulatory review. Overall survival for the combination remains immature, with follow-up ongoing, and no pricing or regulatory decision date for the combination was disclosed in the available material.