FDA approves Inluriyo plus Verzenio for ESR1 mutated advanced breast cancer

The U.S. Food and Drug Administration has approved Eli Lilly’s Inluriyo, also known as imlunestrant, in combination with Verzenio, or abemaciclib, for certain adults with advanced or metastatic breast cancer.

The approval covers adults with estrogen receptor positive, HER2 negative, ESR1 mutated locally advanced or metastatic breast cancer whose disease has progressed following at least one line of endocrine therapy.

Patients must have an ESR1 mutation identified using an FDA authorised test.

The decision is supported by findings from the Phase III EMBER 3 trial, which evaluated Inluriyo alone and in combination with Verzenio in patients whose tumours carried an ESR1 mutation.

Among 159 patients with ESR1 mutated metastatic breast cancer, 92 received Inluriyo alone and 67 were treated with the combination.

Patients had previously received an aromatase inhibitor, either with or without a CDK4/6 inhibitor, in the adjuvant or metastatic setting.

Treatment with Inluriyo plus Verzenio doubled median progression free survival compared with Inluriyo alone.

Median progression free survival reached 11.1 months with the combination compared with 5.5 months for Inluriyo monotherapy.

The hazard ratio was 0.53, with a 95% confidence interval ranging from 0.35 to 0.80.

Jacob Van Naarden, Executive Vice President and President of Lilly Oncology, said the full approval expands the treatment options available to patients with ER positive, HER2 negative, ESR1 mutated metastatic breast cancer.

He said the combination is aligned with an approach of changing treatment when clinical progression occurs and does not introduce additional monitoring requirements beyond those already associated with the individual therapies.

Komal Jhaveri, MD, FACP, FASCO, principal investigator for the EMBER 3 and EMBER 4 trials, said there remains an urgent need for effective treatments after disease progression on adjuvant or first line therapy.

She said targeting both the estrogen receptor and CDK4/6 pathways can help address treatment resistance and highlighted the progression free survival achieved with imlunestrant plus abemaciclib in EMBER 3.

ESR1 mutations develop in around half of patients with ER positive, HER2 negative metastatic breast cancer during or after treatment with aromatase inhibitors.

These mutations can cause estrogen receptors to remain active and continue driving tumour growth.

Inluriyo is an oral estrogen receptor antagonist that works by degrading mutated estrogen receptors, while Verzenio inhibits CDK4 and CDK6 proteins involved in cancer cell division.

Most adverse events reported with the combination in EMBER 3 were Grade 1 or Grade 2.

The most common adverse reactions and laboratory abnormalities occurring in at least 10% of patients included decreased neutrophils, diarrhoea, reduced haemoglobin and lymphocytes, nausea, decreased platelets, fatigue, infections, increased liver enzymes and creatinine, vomiting, musculoskeletal pain, reduced appetite, rash, cough, headache and weight loss.

Permanent discontinuation of Inluriyo because of adverse reactions occurred in 1% of patients in the combination arm, while 3.4% permanently discontinued Verzenio.

This is the second FDA approval for Inluriyo in less than a year.

The medicine was first approved in September 2025 as a monotherapy for adults with ER positive, HER2 negative, ESR1 mutated metastatic breast cancer following progression after at least one line of endocrine therapy.

Lilly is also evaluating Inluriyo in the Phase III EMBER 4 study in patients with ER positive, HER2 negative early breast cancer who are at increased risk of recurrence after standard endocrine therapy.

More than 8,000 patients have been enrolled in EMBER 4 across over 650 sites in more than 30 countries, with initial results expected in 2027.

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Related Topics and Keywords

abemaciclib, breast cancer, Eli Lilly, esr1, FDA Approval, Inluriyo (imlunestrant), metastatic breast cancer, Oncology, pharma news, Phase 3 EMBER-3, verzenio