Eli Lilly announces results from the Phase 3 EMBER-3 study

Eli Lilly (LLY) and Company announced results from the Phase 3 EMBER-3 study of imlunestrant, an investigational, oral selective estrogen receptor degrader, or SERD, in patients with estrogen receptor positive human epidermal growth factor receptor 2 negative, or HER2- advanced breast cancer, or ABC, whose disease progressed on a prior aromatase inhibitor, or AI, with or without a CDK4/6 inhibitor. Imlunestrant demonstrated a statistically significant and clinically meaningful improvement in progression-free survival, or PFS, as monotherapy in patients with an ESR1 mutation versus standard of care endocrine therapy, or SOC ET, reducing the risk of disease progression or death by 38%. Imlunestrant in combination with Verzenio reduced the risk of progression or death by 43% versus imlunestrant alone, in all patients. These results were published in The New England Journal of Medicine and will be shared in a late-breaking oral presentation at the San Antonio Breast Cancer Symposium. In the EMBER-3 study, patients were randomized 1:1:1 to receive imlunestrant alone, SOC ET, or the imlunestrant-abemaciclib combination. Randomization was stratified by prior CDK4/6 inhibitor use, the presence of visceral metastases and geographic region. Imlunestrant significantly improved PFS versus SOC ET in patients with an ESR1 mutation. In patients with an ESR1 mutation, median PFS was 5.5 months with imlunestrant versus 3.8 months with SOC ET; p-valueless than0.001). The overall response rate, or ORR, with imlunestrant was 14% compared to 8% with SOC ET in patients with an ESR1 mutation. In all patients, the median PFS was 5.6 months with imlunestrant versus 5.5 months with SOC ET; p-value 0.12) and did not reach statistical significance. Consistent with preclinical data demonstrating central nervous system penetrance and CNS-activity of imlunestrant, CNS progression rates from a post-hoc analysis were lower with imlunestrant in all patients, as well as patients with an ESR1 mutation, however, these analyses are limited by low event numbers and lack of mandated serial asymptomatic CNS imaging in all patients. Imlunestrant-abemaciclib significantly improved PFS compared to imlunestrant in all patients, regardless of ESR1 mutation status, with median PFS of 9.4 months for imlunestrant-abemaciclib versus 5.5 months for imlunestrant alone. The PFS benefit of the combination was consistent across subgroups, regardless of ESR1 mutation, or PI3K pathway mutation status, and including in patients who had previously received CDK4/6 inhibitor treatment. In all patients, the ORR with imlunestrant-abemaciclib was 27% compared to 12% with imlunestrant alone. Overall survival results for EMBER-3 were immature at the time of analysis. The trial will continue to assess OS as a secondary endpoint.