Indianapolis – September 20, 2026 -- The U.S. Food and Drug Administration has granted full approval to Eli Lilly and Company's (NYSE: LLY) Inluriyo (imlunestrant) in combination with Verzenio (abemaciclib) for adults with estrogen receptor-positive (ER+), HER2-negative, ESR1-mutated locally advanced or metastatic breast cancer whose disease progressed after at least one line of endocrine therapy.
EMBER-3 trial shows combination doubles progression-free survival
The approval rests on Phase 3 EMBER-3 data in 159 patients with ESR1-mutated metastatic breast cancer who had previously received an aromatase inhibitor, with or without a CDK4/6 inhibitor. Patients randomized to Inluriyo plus Verzenio (n=67) achieved a median progression-free survival of 11.1 months, versus 5.5 months for Inluriyo alone (n=92), a hazard ratio of 0.53 (95% CI, 0.35–0.80).
Lilly says Inluriyo now leads the oral SERD category
"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. He said switching both endocrine therapy and the CDK4/6 inhibitor at clinical progression avoids early exposure to added side effects, unnecessary testing anxiety, and avoidable healthcare costs.
Combination targets estrogen receptor and cell-division pathways simultaneously
ESR1 mutations develop in roughly half of ER+, HER2-negative metastatic breast cancer patients during or after aromatase inhibitor treatment, driving overactive estrogen receptor signaling. Inluriyo degrades the mutated estrogen receptor while Verzenio inhibits proteins controlling cancer cell division. Komal Jhaveri, MD, of Memorial Sloan Kettering Cancer Center and principal investigator for EMBER-3 and EMBER-4, said the dual-pathway approach addresses treatment resistance with a safety profile consistent with each drug individually.
Trial data show high rates of diarrhea and neutrophil decline
In EMBER-3, diarrhea occurred in 86% of combination-arm patients, with Grade 3 or 4 cases in 9%. Neutrophil count decreases occurred in 86% of patients, with Grade 3 or 4 decreases in 21%. Interstitial lung disease or pneumonitis occurred in 2.9% of patients. Permanent discontinuation of Inluriyo alone due to adverse reactions occurred in 1% of combination-arm patients, and discontinuation of Verzenio alone occurred in 3.4%.
This marks Lilly's second FDA approval for Inluriyo in under a year, following its September 2025 clearance as monotherapy. The drug is also being tested in the Phase 3 EMBER-4 trial, an adjuvant-setting study enrolling more than 8,000 patients across 650-plus sites in over 30 countries, with initial results expected in 2027. The Inluriyo-Verzenio combination is now available in the United States.