FDA Approves Imlunestrant Plus Abemaciclib for Breast Cancer

Last Friday, September 18, the FDA approved imlunestrant (Inluriyo) in combination with abemaciclib (Verzenio), both manufactured by Eli Lilly and Company, for adults with estrogen receptor (ER)-positive, HER2-negative, ESR1-mutated advanced or metastatic breast cancer with disease progression following at least one line of endocrine therapy.¹

Imlunestrant is an oral ER antagonist, and abemaciclib is a CDK4/6 inhibitor. The FDA also approved the Guardant360 CDx assay as a companion diagnostic device to identify patients with ESR1-mutated breast cancer for treatment with imlunestrant and abemaciclib.

"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,” Jacob Van Naarden, executive vice president and president of Lilly Oncology, said in a news release.²

EMBER-3 Data Support Second Imlunestrant Approval

The decision marks the second FDA approval for imlunestrant in less than a year, the first being its September 2025 approval as a monotherapy to treat adults with ER-positive, HER2-negative, ESR1-mutated metastatic breast cancer whose disease progressed after at least one line of endocrine therapy.³

The most recent approval was based on the results of the phase 3 EMBER-3 trial (NCT04975308), a randomized, open-label, active-controlled, multicenter trial that enrolled adult patients with ER-positive, HER2-negative, locally advanced or metastatic breast cancer.² Of the study population, 92 received imlunestrant, and 67 received imlunestrant in combination with abemaciclib after an aromatase inhibitor, either alone or alongside a CDK4/6 inhibitor.

Among patients with ESR1-mutated metastatic breast cancer, imlunestrant plus abemaciclib doubled median progression-free survival (PFS) vs imlunestrant alone. Median PFS was 11.1 vs 5.5 months (HR, 0.53; 95% CI, 0.35-0.80), with objective response rates of 35% vs 15%, respectively.

“We have an urgent need for effective and safe treatment options for patients with disease progression on adjuvant or first-line therapy…” Komal Jhaveri, MD, section head of the Endocrine Therapy Research Program at Memorial Sloan Kettering Cancer Center and principal investigator of the EMBER-3 trials, said in a news release. “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."

Safety, Dosing, and Future Development

Regarding safety, the imlunestrant prescribing information includes warnings and precautions for embryo-fetal toxicity. The abemaciclib prescribing information also includes warnings and precautions for embryo-fetal toxicity, as well as diarrhea, neutropenia, hepatotoxicity, venous thromboembolism, and interstitial lung disease or pneumonitis.

The recommended dosage of imlunestrant is 400 mg orally once daily, taken on an empty stomach at least 2 hours before or 1 hour after food intake. When used in combination with imlunestrant, the recommended dosage of abemaciclib is 150 mg orally twice daily, with or without food, until disease progression or unacceptable toxicity.

Looking ahead, imlunestrant is also being studied in the phase 3 EMBER-4 trial in the adjuvant setting for people with ER-positive, HER2-negative, early-stage breast cancer who are at increased risk of recurrence following standard-of-care endocrine therapy. The trial is the largest adjuvant oral selective ER degrader clinical trial, with more than 8000 patients enrolled at more than 650 sites across more than 30 countries. Initial results are anticipated in 2027.

References

1. FDA approves imlunestrant in combination with abemaciclib for ER-positive, HER2-positive, HER2-negative, ESR1-mutated advanced or metastatic breast cancer. News release. FDA. September 18, 2026. Accessed September 21, 2026. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-imlunestrant-combination-abemaciclib-er-positive-her2-negative-esr1-mutated-advanced-or
2. US FDA approves Inluriyo (imlunestrant) in combination with Verzenio (abemaciclib) for adults with ER+, HER2-, ESR1-mutated advanced or metastatic breast cancer. News release. Eli Lilly and Company. September 18, 2026. Accessed September 21, 2026. https://investor.lilly.com/news-releases/news-release-details/us-fda-approves-inluriyo-imlunestrant-combination-verzenio
3. McCrear S. FDA approves imlunestrant for ER+ and HER2-negative breast cancer. AJMC^®. September 25, 2025. Accessed September 21, 2026. https://www.ajmc.com/view/fda-approves-imlunestrant-for-er-and-her2-negative-breast-cancer