The U.S. Food and Drug Administration has granted full approval to Eli Lilly’s Inluriyo (imlunestrant) in combination with Verzenio (abemaciclib) for adults with advanced breast cancer.

 

Lilly said the approval is based on results from the Phase 3 EMBER-3 trial, where the combination doubled median progression-free survival compared with Inluriyo alone among patients with ESR1-mutated metastatic breast cancer.

 

Patients receiving Inluriyo plus Verzenio had a median progression-free survival of 11.1 months, compared with 5.5 months for those receiving Inluriyo alone. The reported hazard ratio was 0.53.

 

"In less than a year since its approval, Inluriyo is the leading treatment option for people with ER+, HER2–, ESR1m metastatic breast cancer, now reaching over half of all patients starting an oral SERD," said Jacob Van Naarden, executive vice president and president of Lilly Oncology. 

 

"Today's full approval extends what Inluriyo in combination with Verzenio can do for patients, with a regimen that has confirmed benefit, is aligned to the clinically proven treatment paradigm of changing therapy at clinical progression, and doesn't introduce burdensome monitoring requirements for patients or physicians. In fact, all available evidence suggests that switching endocrine therapy and CDK4/6 inhibitor at clinical progression improves patient outcomes more than switching therapy earlier. 

 

"Utilizing this evidence-based practice spares early exposure to additional side effects, reduces patient anxiety from unnecessary testing, and mitigates avoidable costs to the healthcare system."

 

The approval covers patients whose tumors carry an ESR1 mutation, a genetic alteration that can emerge during or after treatment with aromatase inhibitors and contribute to resistance to endocrine therapy.

 

Inluriyo targets the estrogen receptor, while Verzenio blocks CDK4/6 proteins involved in cell division. Lilly says the combination is intended to attack two key drivers of ER-positive breast cancer and is administered entirely by mouth.

 

"We have an urgent need for effective and safe treatment options for patients with disease progression on adjuvant or first-line therapy. Combining therapies that work on two distinct drivers of tumor growth—the estrogen receptor and CDK4/6—is an important strategy to help address treatment resistance," said Komal Jhaveri, principal investigator for the EMBER-3 and EMBER-4 trials. 

 

"In EMBER-3, switching both the endocrine therapy and CDK 4/6 inhibitor, for the majority of patients, to imlunestrant plus abemaciclib at disease progression achieved a median progression-free survival of 11.1 months and a safety profile consistent with that of each medicine individually, establishing a meaningful new treatment option."

 

The EMBER-3 analysis included 159 patients with ESR1-mutated metastatic breast cancer. Of those, 92 received Inluriyo alone and 67 received the combination with Verzenio after treatment with an aromatase inhibitor, with or without a CDK4/6 inhibitor.

 

The safety profile reflected known risks associated with the medicines. Lilly reported that most adverse events in the combination arm were Grade 1 or 2. The most common reactions included reduced neutrophil counts, diarrhea, reduced hemoglobin and lymphocytes, nausea, fatigue, infections, liver-enzyme increases, vomiting, musculoskeletal pain and rash.

 

Serious adverse reactions occurred in 21% of patients receiving the combination, while fatal adverse reactions occurred in 3.8%, according to Lilly. The drug labels include warnings and precautions covering risks including severe diarrhea, neutropenia, interstitial lung disease or pneumonitis, hepatotoxicity, venous thromboembolism and embryo-fetal toxicity.

 

The FDA decision marks the second approval for Inluriyo in less than a year. The drug was approved in September 2025 as a standalone treatment 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.

 

Lilly is also testing Inluriyo in earlier-stage disease. Its Phase 3 EMBER-4 trial is evaluating the drug as an adjuvant treatment for people with ER-positive, HER2-negative early breast cancer at increased risk of recurrence following standard endocrine therapy, including treatment with CDK4/6 inhibitors.