Updated Data for Lilly’s Inluriyo™ (imlunestrant) Reinforce Efficacy as Monotherapy and in Combination with Verzenio® (abemaciclib) in ER+, HER2– Advanced Breast Cancer
Eli Lilly and Company today announced updated results from the Phase 3 EMBER-3 study of Inluriyo (imlunestrant), an oral estrogen receptor antagonist, in patients with estrogen receptor positive (ER+), human epidermal growth factor receptor 2–negative (HER2–) advanced or metastatic breast cancer (MBC), whose disease progressed on a prior aromatase inhibitor (AI), with or without a CDK4/6 inhibitor.
As monotherapy, imlunestrant demonstrated a clinically meaningful 38% reduction in the risk of progression or death (median PFS 5.5 vs 3.8 months; HR=0.62 [95% CI 0.47–0.82]; nominal p=0.0007) and demonstrated an 11.4-month improvement in median OS (34.5 vs 23.1 months; HR=0.60 [95% CI 0.43–0.86]; p=0.0043; boundary for significance not met) versus endocrine therapy, in patients with ESR1-mutated disease. In all patients, imlunestrant plus abemaciclib reduced the risk of progression or death by 41% versus imlunestrant alone, demonstrated a favorable OS trend and numerically delayed time to chemotherapy (TTC) by more than a year.
These results were published in Annals of Oncology and will be shared in a late-breaking oral presentation at the San Antonio Breast Cancer Symposium (SABCS) today, Friday, December 12, at 10:45 AM CT / 11:45 AM ET.
“Following the recent FDA approval of Inluriyo as monotherapy, these updated data Reinforce demonstrate continued clinically meaningful benefit—both for patients receiving monotherapy and those receiving the combination with abemaciclib—and further reinforce its role in this treatment setting,” said Jacob Van Naarden, executive vice president and president, Lilly Oncology. “Given the important role of CDK4/6 inhibitors in treating ER+, HER2– metastatic breast cancer, we’re encouraged by the potential of an all-oral combination with imlunestrant and abemaciclib and have submitted these combination data for U.S. regulatory review in ESR1-mutated MBC.”
Results for the imlunestrant plus abemaciclib combination were consistent with previous efficacy results and demonstrated durable benefit across efficacy endpoints, regardless of ESR1 mutation status. In all patients, median PFS was nearly doubled versus imlunestrant alone (10.9 vs 5.5 months; HR=0.59 [95% CI 0.47–0.74]; nominal p<0.0001), and a favorable OS trend was observed (HR=0.82 [95% CI 0.59–1.16]), with continued separation of survival curves.
Median TTC was numerically extended by more than a year (27.8 vs 15.5 months) versus imlunestrant alone. In patients with ESR1-mutated disease, median PFS was extended to 11.0 months versus 5.6 months with imlunestrant alone (HR=0.55 [95% CI 0.41–0.74]; nominal p<0.001). Notably, most patients (65%) in the combination arm had previously received a CDK4/6 inhibitor.
“With an additional year of follow-up, these results Inluriyo strengthen the case for imlunestrant-based regimens in ER+, HER2– metastatic breast cancer,” said Komal Jhaveri, MD, FACP, FASCO, Associate Attending Breast Medicine and Early Drug Development Services, section head of Endocrine Therapy Research Program at Memorial Sloan Kettering Cancer Center, and one of the study’s principal investigators. “The median progression-free survival of 11 months is among the longest we’ve seen in this population, and just as importantly, patients are living longer without needing chemotherapy.”
Safety across imlunestrant-based regimens was consistent with previous reports, and no new safety signals were observed with this additional follow-up. Follow-up for OS is ongoing, and additional analyses are planned as data mature.
Imlunestrant is also being investigated in the adjuvant setting in people with ER+, HER2– early breast cancer with an increased risk of recurrence. The Phase 3 EMBER-4 trial completed enrollment of approximately 8,000 patients following two to five years of adjuvant endocrine therapy in the context of the established CDK4/6i standard of care.
About EMBER-3
EMBER-3 is a Phase 3, randomized, open-label study of imlunestrant, investigator’s choice of endocrine therapy, and imlunestrant in combination with abemaciclib in patients with ER+, HER2– locally advanced or metastatic breast cancer whose disease has recurred or progressed during or following an aromatase inhibitor (AI) therapy with or without a CDK 4/6 inhibitor.
The trial enrolled 874 adult patients, 32% of which enrolled from the adjuvant setting into first-line treatment of MBC and 64% as second-line treatment following progression on initial therapy for MBC. Enrolled trial participants were randomized between imlunestrant, investigator’s choice of fulvestrant or exemestane, or plus abemaciclib. Randomization was stratified by prior CDK4/6 inhibitor use, the presence of visceral metastases and geographic region.
Patients enrolled as first line (1L) treatment for ABC (32%), following disease recurrence on or within 12 months of completing adjuvant AI, with or without CDK4/6 inhibitor for early breast cancer (EBC), or as second line (2L) treatment for ABC (64%), following progression on AI, with or without CDK4/6 inhibitor as initial therapy for ABC. Primary endpoints were investigator-assessed PFS of imlunestrant versus SOC ET therapy in patients with ESR1 mutations, imlunestrant versus SOC ET in all patients, and Imlunestrant plus abemaciclib versus imlunestrant in all patients. More information on the EMBER-3 study can be found on clinicaltrials.gov.
About Metastatic/Advanced Breast Cancer
Metastatic/advanced breast cancer (ABC) is a cancer that has spread from the breast tissue to other parts of the body. Locally Inluriyo advanced breast cancer means the cancer has grown outside the organ where it started but has not yet spread to other parts of the body.1 Of all high risk early-stage breast cancer cases diagnosed in the U.S., approximately 30% will become metastatic2 and an estimated 6-10% of all new breast cancer cases are initially diagnosed as being metastatic.3
Survival is lower among women with a more advanced stage of disease at diagnosis: five-year relative survival is 99% for localized disease, 86% for regional/locally advanced disease, and 30% for metastatic/advanced disease.4 Other factors, such as tumor size, also impact five-year survival estimates.4
About Breast Cancer
Breast cancer is the second most commonly diagnosed cancer worldwide (following lung cancer), according to GLOBOCAN. The estimated 2.3 million new cases indicate that close to 1 in every 4 cancers diagnosed in 2022 is breast cancer. With Inluriyo approximately 666,000 deaths in 2022, breast cancer is the fourth-leading cause of cancer death worldwide.5 In the U.S., it is estimated that there will be more than 310,000 new cases of breast cancer diagnosed in 2024. Breast cancer is the second leading cause of cancer death in women in the U.S.6
About Inluriyo™ (imlunestrant)
Inluriyo (imlunestrant) is an oral estrogen receptor antagonist that delivers continuous ER inhibition, including in ESR1-mutant cancers. The estrogen receptor (ER) is the key therapeutic target for patients with estrogen receptor-positive (ER+), human epidermal growth factor receptor 2-negative (HER2–) breast cancer. Inluriyo is a U.S. FDA approved oral prescription medicine.
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