FDA Approves Lilly’s Inluriyo Oral Therapy for ESR1-Mutated Metastatic Breast Cancer

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Key Takeaways

Inluriyo is the first oral therapy approved for ER-positive, HER2-negative, ESR1-mutated advanced breast cancer, offering an alternative to injectable endocrine therapies.
The Phase III EMBER-3 trial showed Inluriyo improved progression-free survival by 38% compared to standard endocrine therapy.
Inluriyo provides continuous estrogen receptor inhibition, including for ESR1 mutations, and is under evaluation for various breast cancer types.
The drug's oral administration and tolerability profile offer flexibility and a meaningful alternative for patients with ESR1-mutated metastatic breast cancer.

FDA approves Eli Lilly’s Inluriyo (imlunestrant) for adults with ER-positive, HER2-negative, ESR1-mutated advanced or metastatic breast cancer that has progressed after endocrine therapy.

Image Credit: Adobe Stock Images/Lars Neumann. Inluriyo is a brain-penetrant, oral selective ER degrader that has been shown to provide continuous ER inhibition, including for ESR1-mutant cancers.

The FDA has approved Eli Lilly’s Inluriyo (imlunestrant) to treat adults with estrogen receptor (ER)-positive, HER2-negative, ESR1-mutated advanced or metastatic breast cancer whose disease progressed following endocrine therapy (ET).

FDA approval expands treatment options for ESR1-mutated metastatic breast cancer

The once-daily ER antagonist is the first oral therapy of its kind indicated for this patient population and offers an alternative to injectable ET.¹

"This therapy reflects our commitment to developing treatments that improve outcomes for people with breast cancer and represents an important step toward advancing innovative, all-oral treatment approaches," Jacob Van Naarden, executive vice president and president of Lilly Oncology, said in a press release. "We are deeply grateful to the patients, investigators, Lilly team members and clinical care teams who made this advancement possible. This therapy has the potential to make the treatment journey more manageable for those living with breast cancer."¹

"This represents an important advancement for patients with ESR1-mutated [metastatic breast cancer], a mutation found in nearly half of patients who have taken hormone therapies, often contributing to treatment resistance. With its demonstrated efficacy, tolerability profile and oral administration, this therapy provides a meaningful alternative treatment option for this patient population."

The regulatory action was based on findings from the Phase III EMBER-3 trial (NCT04975308), which were also published by The New England Journal of Medicine.^2,3 Results from the trial show that Inluriyo prolonged progression-free survival (PFS) by 38% compared with ET.

"The approval of Inluriyo expands the metastatic breast cancer treatment landscape for patients who test positive for the ESR1 mutation," said Jean Sachs, CEO, Living Beyond Breast Cancer, in the press release. "Eligible patients will now have access to an additional treatment option, offering them the potential for flexibility in their daily lives and disease management, and above all, renewed hope for the future."¹

**Inluriyo delivers continuous estrogen receptor inhibition, including ESR1 mutations**

Inluriyo is a brain-penetrant, oral selective ER degrader that has been shown to provide continuous ER inhibition, including for ESR1-mutant cancers.
The drug is currently under evaluation across multiple clinical trials for different breast cancer types.

Phase III EMBER-3 trial shows 38% reduction in risk of progression

The randomized, open-label EMBER-3 trial included 874 adults with ER-positive, HER2-negative, locally advanced or metastatic breast cancer whose disease recurred or progressed during or after treatment with aromatase inhibitor therapy, with or without a CDK 4/6 inhibitor.
Patients were randomly assigned in a 1:1:1 ratio to receive Inluriyo, standard endocrine monotherapy, or Inluriyo plus Verzenio.
The primary endpoints were investigator-assessed PFS with Inluriyo compared to standard therapy among patients with ESR1 mutations and among all patients, and comparison of Inluriyo plus Verzenio vs. Inluriyo monotherapy among all patients who underwent randomization concurrently.
A total of 32% of patients were enrolled from the adjuvant setting into first-line treatment for advanced breast cancer and 64% as second-line treatment after progressing on initial therapy for advanced breast cancer.
Among 256 patients with ESR1 mutations, median PFS was 5.5 months with Inluriyo compared to 3.8 months with standard therapy.
At 19.4 months, estimated restricted mean survival time was 7.9 months among patients treated with Inluriyo compared to 5.4 months among patients given standard therapy.
For the overall patient population, median PFS was 5.6 months for those treated with Inluriyo vs. 5.5 months with standard therapy.
Incidence of grade 3 or higher adverse events was 17.1% in the Inluriyo monotherapy cohort, 20.7% in the standard therapy cohort, and 48.6% in the Inluriyo plus Verzenio cohort.

Approval offers flexibility and oral alternative to injectable endocrine therapies

"This represents an important advancement for patients with ESR1-mutated metastatic breast cancer, a mutation found in nearly half of patients who have taken hormone therapies, often contributing to treatment resistance," EMBER-3 trial principal investigator Komal Jhaveri, MD, FACP, FASCO, section head of Endocrine Therapy Research and clinical director of Early Drug Development at Memorial Sloan Kettering Cancer Center, said in the release. "With its demonstrated efficacy, tolerability profile and oral administration, this therapy provides a meaningful alternative treatment option for this patient population."¹

References

1. U.S. FDA approves Inluriyo (imlunestrant) for adults with ER+, HER2-, ESR1-mutated advanced or metastatic breast cancer. News release. Eli Lilly. September 25, 2025. Accessed September 25, 2025. https://investor.lilly.com/news-releases/news-release-details/us-fda-approves-inluriyo-imlunestrant-adults-er-her2-esr1

2. A Study of Imlunestrant, Investigator's Choice of Endocrine Therapy, and Imlunestrant Plus Abemaciclib in Participants With ER+, HER2- Advanced Breast Cancer (EMBER-3). ClinicalTrials.gov. Updated July 11, 2025. Accessed September 25, 2025. https://clinicaltrials.gov/study/NCT04975308

3. Jhaveri k., et al. Imlunestrant with or without Abemaciclib in Advanced Breast Cancer. N Engl J Med 2024. DOI: 10.1056/NEJMoa2410858.

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