Inluriyo (imlunestrant)

In September 2025, imlunestrant was approved for the treatment of adults with ER+, HER2-, ESR1-mutated advanced or metastatic breast cancer with disease progression following at least one line of endocrine therapy in the USA. This article summarizes the milestones in the development of imlunestrant leading to this first approval for use in patients with ER+, HER2-, ESR1-mutated advanced or metastatic breast cancer.

P2, N=42, Not yet recruiting, Jonsson Comprehensive Cancer Center | Trial completion date: Sep 2031 --> Apr 2031 | Initiation date: Sep 2025 --> Apr 2026 | Trial primary completion date: Sep 2030 --> Apr 2030

P2, N=42, Not yet recruiting, Jonsson Comprehensive Cancer Center

P1, N=193, Active, not recruiting, Eli Lilly and Company | Trial primary completion date: May 2025 --> Dec 2025

Imlunestrant was well tolerated as an oral solution or as a tablet/intravenous dose. Eight participants reported mild/moderate treatment-related adverse events that resolved by the end of the study.

In vivo, imlunestrant outperformed fulvestrant leading to tumor regression in a patient derived xenograft harboring the Y537S ESR1 mutation. Additionally, a genome wide CRISPR knock-out screen identified several vulnerabilities that were either persistent or gained after imlunestrant treatment, providing a rationale for future studies of combination treatments with imlunestrant. Collectively, these results highlight the on-target and selective activity of imlunestrant, which can circumvent resistance engendered by the Y537S ESR1 mutation.

P1, N=193, Active, not recruiting, Eli Lilly and Company | Trial completion date: May 2025 --> Dec 2025

P1, N=17, Active, not recruiting, Eli Lilly and Company | Trial completion date: Dec 2025 --> Dec 2026

P3, N=8000, Recruiting, Eli Lilly and Company | N=6000 --> 8000

The phase 3 EMBER-3 trial1 demonstrated that when compared to standard therapy, imlunestrant improved progression-free survival (PFS) in advanced ER+/HER2- breast cancer with ESR1 mutations. When combined with abemaciclib, it significantly improved PFS for the entire population. However, the absence of a biomarker-based control group limits broader conclusions, highlighting the need for trials incorporating specific standards in ER+/HER2- breast cancer.

There are currently five oral SERDs in published and ongoing clinical trials-elacestrant, camizestrant, giredestrant, imlunestrant, and amcenestrant-with more in development. They offer a reasonably well-tolerated oral therapy option with low discontinuation rates in studies. This review summarizes the currently available literature on this new class of drugs.

Among patients with ER-positive, HER2-negative advanced breast cancer, treatment with imlunestrant led to significantly longer progression-free survival than standard therapy among those with ESR1 mutations but not in the overall population. Imlunestrant-abemaciclib significantly improved progression-free survival as compared with imlunestrant, regardless of ESR1-mutation status. (Funded by Eli Lilly; EMBER-3 ClinicalTrials.gov number, NCT04975308.).