Companion Diagnostic Earns FDA Approval for Imlunestrant in Breast Cancer

The FDA has approved the Guardant360® CDx test as a companion diagnostic to identify patients with ESR1-mutant advanced breast cancer who may benefit from imlunestrant (Inluriyo), according to a news release from the developer, Guardant Health.¹ Furthermore, the assay was approved in conjunction with imlunestrant for the treatment of adult patients with estrogen receptor (ER)–positive, HER2-negative, ESR1-mutated advanced or metastatic breast cancer who experienced disease progression following 1 or more prior lines of endocrine therapy.²

“This FDA approval provides another treatment for [patients with] breast cancer with ESR1 mutations for their specific type of cancer along with expanded access to comprehensive genomic profiling with a simple blood draw,” Helmy Eltoukhy, chairman and co-chief executive officer of Guardant Health, said in the news release.¹ “Precision testing plays a critical role in helping physicians identify the correct treatment, providing patients and their doctors with the comprehensive genomic profiling needed to see if they are eligible to receive the right treatment and improving outcomes.”

In the phase 3 EMBER-3 trial (NCT04975308), which assessed imlunestrant alone or with abemaciclib (Verzenio) vs standard-of-care (SOC) endocrine therapy, imlunestrant exhibited an efficacy benefit in the ESR1-mutated population. According to findings presented at the 2024 San Antonio Breast Cancer Symposium (SABCS) and subsequently published in the New England Journal of Medicine, the median progression-free survival (PFS) was 5.5 months (95% CI, 3.9-7.4) among patients treated with imlunestrant vs 3.8 months (95% CI, 3.7-5.5) among those treated with SOC endocrine therapy.^3,4

In the open-label phase 3 trial, patients 18 years or older with locally confirmed and measurable disease per RECIST v1.1 criteria were randomly assigned 1:1:1 to receive oral imlunestrant at 400 mg once daily alone (n = 331), imlunestrant with oral abemaciclib at 150 mg twice daily (n = 213), or SOC endocrine therapy consisting of oral exemestane (Aromasin) at 25 mg or fulvestrant at 500 mg injected intramuscularly on days 1 and 15 of cycle 1 and day 1 of each 28-day cycle thereafter (n = 330).

Among patients with ESR1-mutant disease who were treated with imlunestrant monotherapy (n = 138) or with SOC endocrine therapy (n = 118), the median age was 61 years (range, 28-85) vs 60 years (33-85), and all patients were women. A total of 88.4% vs 89.0% were postmenopausal, 58.0% vs 64.4% were White, and 45.7% vs 45.8% were from North America or western Europe.

This patient population primarily had an ECOG performance status of 0 (61.6% vs 65.3%), measurable disease at baseline (81.2% vs 77.1%), and visceral metastases (60.9% vs 56.8%). Additionally, most of this patient subset had secondary endocrine resistance (100% each), had received the most recent dose of endocrine therapy for advanced breast cancer (73.2% vs 77.1%), and had received prior CDK4/6 inhibition (67.4% vs 72.0%).

The primary end points were investigator-assessed PFS with imlunestrant monotherapy vs SOC endocrine therapy in the ESR1-mutated and overall populations, as well as in the overall population between those treated with imlunestrant monotherapy vs imlunestrant with abemaciclib. Overall survival was a key secondary end point among the entire population, with other secondary end points including PFS per blinded independent committee review, overall response rate, and safety.

Regarding safety, most adverse effects (AEs) observed with imlunestrant were grades 1 or 2 in severity. Common toxicities included laboratory abnormalities, calcium decreases, musculoskeletal pain, neutrophil decreases, aspartate aminotransferase increases, fatigue, and diarrhea. AEs leading to dose discontinuation, reduction, or interruption occurred in 4.6%, 2.4%, and 10% of patients, respectively.

The approval of the Guardant360 CDx as a companion diagnostic for imlunestrant is the sixth CDx claim approved by the FDA and the second for breast cancer after an approval as a companion for elacestrant (Orserdu) for the same population in January 2023.⁵

References

1. FDA approves Guardant360® CDx as companion diagnostic for Eli Lilly and Company’s Inluriyo™ (imlunestrant) for treatment of ESR1-mutated advanced breast cancer. News release. Guardant Health. September 29, 2025. Accessed October 1, 2025. https://tinyurl.com/43a2kutj
2. U.S. FDA approves Inluriyo (imlunestrant) for adults with ER+, HER2-, ESR1-mutated advanced or metastatic breast cancer. News release. Eli Lilly and Company. September 25, 2025. Accessed October 1, 2025. https://tinyurl.com/2fexwcem
3. Jhaveri KL, Neven P, Casalnuovo ML, et al. Imlunestrant, an oral selective estrogen receptor degrader (SERD), as monotherapy and combined with abemaciclib, for patients with ER+, HER2- advanced breast cancer (ABC), pretreated with endocrine therapy (ET): results of the phase 3 EMBER-3 trial. Presented at: 2024 San Antonio Breast Cancer Symposium; December 10-14, 2024; San Antonio, TX. Abstract GS1-01.
4. Jhaveri KL, Neven P, Casalnuovo ML, et al. Imlunestrant with or without abemaciclib in advanced breast cancer. N Engl J Med. 2025;392:1189-1202. doi:10.1056/NEJMoa2410858
5. Guardant Health receives FDA approval for Guardant360® CDx as companion diagnostic for Menarini Group's ORSERDU^TM for treatment of patients with ESR1 mutations in ER+, HER2- advanced or metastatic breast cancer. News release. Guardant Health. January 30, 2023. Accessed October 1, 2025. http://bit.ly/3DobE1h