If you wish to report an adverse event or product complaint, please call 1-800-LILLYRX (1-800-545-5979)
Imlunestrant
This information is provided in response to your request. Resources may contain information about doses, uses, formulations and populations different from product labeling.
What are the primary outcome results of the EMBER-3 study?
EMBER-3 demonstrated imlunestrant, as monotherapy or in combination with abemaciclib, is an oral targeted-therapy option for patients with ER+, HER2- ABC after recurrence or progression on or after an aromatase inhibitor ± a CDK 4/6 inhibitor.
EMBER-3: Phase 3 Study of Imlunestrant ± Abemaciclib for Patients With ER+, HER2- Advanced Breast Cancer Following Recurrence or Progression on Previous ET
EMBER-3 (NCT04975308) is a phase 3, randomized, open-label study of imlunestrant monotherapy, investigator's choice of endocrine therapy (fulvestrant or exemestane), and imlunestrant in combination with abemaciclib in patients with estrogen receptor-positive (ER+), human epidermal growth factor receptor 2-negative (HER2-) locally advanced or metastatic breast cancer previously treated with endocrine therapy (aromatase inhibitor) ± a cyclin-dependent kinase (CDK) 4/6 inhibitor.1,2 EMBER-3 Study Design summarizes the EMBER-3 study design.
Figure 1 description: The study schema is presented summarizing the patient population, stratification factors, treatment arms, and endpoints evaluated in EMBER-3.
Abbreviations: ABC = advanced breast cancer; AI = aromatase inhibitor; BICR = blinded independent central review; BID = twice daily; CDK4/6 = cyclin-dependent kinase 4 and 6; ER+ = estrogen receptor-positive; ESR1 = estrogen receptor 1; GnRH = gonadotropin-releasing hormone; HER2- = human epidermal growth factor receptor 2-negative; IM = intramuscularly; N = total population; PFS = progression-free survival; PO = oral; QD = once daily; R = randomization; RECIST = Response Evaluation Criteria in Solid Tumors.
a A GnRH agonist was required in men and premenopausal women.
b Investigator's choice between fulvestrant and exemestane.
c Labeled dosing regimen.
d Enrollment in Arm C started with Protocol Amendment A (at which point 122 patients had been randomized to Arm A and B).
e Analyses performed only if respective primary endpoint has been met.
f Analyses performed in concurrently randomized patients.
Patients were enrolled from October 2021 to November 2023 across 195 sites in 22 countries. Demographics and baseline characteristics were well balanced at study entry. In the overall population
- the median age was 61 years (range, 27 to 89)
- 55.5% had visceral metastases, and
- 59.8% had previously received a CDK 4/6 inhibitor.2
A total of 38.7% patients across the imlunestrant monotherapy group and standard-of-care endocrine therapy (SOC ET) group harbored an estrogen receptor 1 mutation (ESR1m).2
Results: Primary Endpoints
Imlunestrant Versus SOC ET: Investigator-Assessed PFS in Patients With ESR1 Mutations
As shown in Imlunestrant Versus SOC ET: Investigator-Assessed PFS Among Patients With ESR1 Mutations, imlunestrant monotherapy significantly improved investigator-assessed progression-free survival (PFS) compared to SOC ET in patients with ESR1m, with a
- median PFS of 5.5 vs 3.8 months, and
- restricted mean survival time at 19.4 months of 7.9 vs 5.4 months (between-group difference, 2.6 months; 95% CI, 1.2-3.9; p<.001).2
Figure 2 description: The Kaplan-Meier curve displays estimates of progression-free survival for patients with ESR1m that received imlunestrant monotherapy or standard-of-care endocrine therapy in EMBER-3. With 109 and 102 events out of 138 and 118 patients, respectively, median progression-free survival was 5.5 months for patients in the imlunestrant monotherapy group versus 3.8 months for those in the standard-of-care endocrine therapy group. Imlunestrant monotherapy led to a 38% reduction in the risk of progression or death in patients with ESR1m compared to standard therapy. With a hazard ratio equal to 0.62 and 95% confidence interval of 0.46 to 0.82, this result was significant and had a p value of <.001.
Abbreviations: ESR1 = estrogen receptor 1; HR = hazard ratio; PFS = progression-free survival; SOC ET = standard of care endocrine therapy.
Note: Due to evidence of non-proportional hazards, a sensitivity analysis of progression-free survival using restricted mean survival time was conducted. Estimated restricted mean survival time at 19.4 months was 7.9 months in the imlunestrant monotherapy group versus 5.4 months in the standard-of-care endocrine therapy group (difference, 2.6 months; 95% confidence interval, 1.2-3.9; p<.001).
Data cutoff date: June 24, 2024.
Imlunestrant Versus SOC ET: Investigator-Assessed PFS in All Patients
As shown in Imlunestrant Versus SOC ET: Investigator-Assessed PFS Among All Patients, at the primary analysis, the PFS difference of imlunestrant monotherapy vs SOC ET in all patients did not reach significance. The majority subgroup of patients without ESR1m showed no difference in PFS.2
Figure 3 description: The Kaplan-Meier curve displays estimates of progression-free survival for all patients that received imlunestrant monotherapy or standard-of-care endocrine therapy in EMBER-3. With 237 and 253 events out of 331 and 330 patients, respectively, median progression-free survival was 5.6 months for patients in the imlunestrant monotherapy group vs 5.5 months for those in the standard-of-care endocrine therapy group. This difference did not reach statistical significance.
Abbreviations: HR = hazard ratio; PFS = progression-free survival; SOC ET = standard-of-care endocrine therapy.
Data cutoff date: June 24, 2024.
Imlunestrant + Abemaciclib Versus Imlunestrant: Investigator-Assessed PFS in All Patients
As shown in Imlunestrant + Abemaciclib Versus Imlunestrant: Investigator-Assessed PFS Among All Patients, imlunestrant combined with abemaciclib significantly improved investigator-assessed PFS compared to imlunestrant alone in all patients, with a
- median PFS of 9.4 vs 5.5 months, and
- hazard ratio of 0.57, representing a 43% reduction in the risk of progression or death.2
Figure 4 description: The Kaplan-Meier curve displays estimates of progression-free survival for all patients that received imlunestrant in combination with abemaciclib or imlunestrant alone in EMBER-3. With 114 and 149 events out of 213 and 213 patients, respectively, median progression-free survival was 9.4 months for patients in the imlunestrant plus abemaciclib combination group vs 5.5 months for those in the imlunestrant alone group. The improvement in progression-free survival with the combination treatment was significant with a hazard ratio equal to 0.57 and 95% confidence interval of 0.44 to 0.73 resulting in a p value of <.001.
Abbreviations: HR = hazard ratio; PFS = progression-free survival.
Data cutoff date: June 24, 2024.
Safety and Tolerability
Overall, the safety profile of imlunestrant monotherapy was similar to SOC ET, with generally low-grade and manageable side effects, mainly fatigue, diarrhea, and nausea.2,4
In the imlunestrant plus abemaciclib combination arm, diarrhea, nausea, and neutropenia were most frequently reported, and adverse events (AEs) were managed with dose adjustments and supportive medications.2,4
The most frequent AEs in both imlunestrant arms were low grade, reversible, occurred early in treatment, and resulted in few treatment discontinuations.2,4
The incidence of venous thromboembolism, interstitial lung disease, bradycardia, dyslipidemia, and photopsia were relatively low or not observed in both imlunestrant arms.2,4
In general, the safety profile of imlunestrant monotherapy and imlunestrant plus abemaciclib was consistent across age groups.4
EMBER-3: Summary of Adverse Events (Safety Population) and EMBER-3: TEAEs Occurring in ≥10% Patients in Any Treatment Group (Safety Population) summarize the safety profile and commonly reported AEs across the 3 treatment groups in EMBER-3.
Parameter, n (%) |
Imlunestrant Monotherapy |
SOC ET |
Imlunestrant + Abemaciclib |
Patients with ≥1 AE |
270 (82.6) |
273 (84.3) |
204 (98.1) |
Patients with ≥1 grade ≥3 AE |
56 (17.1) |
67 (20.7) |
101 (48.6) |
Patients with ≥1 SAEb |
34 (10.4) |
37 (11.4) |
35 (16.8) |
Patients with AE leading to dose interruption of any study drug |
34 (10.4) |
2 (0.6)c |
115 (55.3)d |
Patients with AE leading to dose reductions of any study drug |
8 (2.4) |
0 |
82 (39.4)e |
Study discontinuation due to AEf |
14 (4.3) |
4 (1.2) |
13 (6.3)g |
Deaths due to AEh |
6 (1.9) |
3 (1.4) |
Abbreviations: AE = adverse event; SAE = serious adverse event; SOC ET = standard-of-care endocrine therapy.
aIncluded 859 patients who initiated treatment.
bSerious adverse event occurring on study and within 30 days of study treatment discontinuation.
cData point represents only dose interruptions (only exemestane). Dose interruptions of exemestane and dose delays of fulvestrant occurred in 7% of patients.
dNinety-two (44.2%) patients had both drugs interrupted, 20 (9.6%) patients had only abemaciclib interrupted, and 3 (1.4%) patients had only imlunestrant interrupted.
eThirty (14.4%) patients had both drugs dose reduced, 48 (23.1%) patients had only abemaciclib reduced, and 4 (1.9%) patients had only imlunestrant reduced.
fDose discontinuations include fatal AEs.
gDiscontinued all study treatment. One (0.5%) more patient discontinued only imlunestrant and 6 (2.9%) more patients discontinued only abemaciclib.
hIncluded deaths occurred on study and within 30 days of treatment discontinuation. Deaths are also included as serious adverse events and discontinuations due to adverse events.
iOne additional patient was reported to have died due to study disease but also experienced a serious adverse event of septic shock due to dengue infection considered fatal by the investigator.
jOne death due to right ventricular failure was considered by the investigator to be related to the study treatment. Concomitant rapid disease progression with florid bone marrow disease prevented the assessment of the exact cause of death.
Eventb, n (%) |
Imlunestrant Monotherapy |
SOC ET |
Imlunestrant + Abemaciclib |
|||
|
Any Grade |
Grade ≥3 |
Any Grade |
Grade ≥3 |
Any Grade |
Grade ≥3 |
Patients with ≥1 TEAE |
270 (82.6) |
56 (17.1) |
273 (84.3) |
67 (20.7) |
204 (98.1) |
101 (48.6) |
Fatiguec |
74 (22.6) |
1 (0.3) |
43 (13.3) |
2 (0.6) |
80 (38.5) |
10 (4.8) |
Diarrhea |
70 (21.4) |
1 (0.3) |
38 (11.7) |
0 |
179 (86.1) |
17 (8.2) |
Nausea |
56 (17.1) |
1 (0.3) |
42 (13.0) |
0 |
101 (48.6) |
4 (1.9) |
Arthralgia |
46 (14.1) |
2 (0.6) |
46 (14.2) |
1 (0.3) |
19 (9.1) |
1 (0.5) |
AST increased |
41 (12.5) |
3 (0.9) |
41 (12.7) |
3 (0.9) |
34 (16.3) |
5 (2.4) |
Back pain |
35 (10.7) |
2 (0.6) |
23 (7.1) |
1 (0.3) |
10 (4.8) |
1 (0.5) |
ALT increased |
34 (10.4) |
1 (0.3) |
33 (10.2) |
2 (0.6) |
28 (13.5) |
10 (4.8) |
Anemiac |
33 (10.1) |
7 (2.1) |
41 (12.7) |
9 (2.8) |
91 (43.8) |
16 (7.7) |
Abdominal painc |
29 (8.9) |
1 (0.3) |
18 (5.6) |
2 (0.6) |
41 (19.7) |
4 (1.9) |
Vomiting |
29 (8.9) |
2 (0.6) |
16 (4.9) |
1 (0.3) |
65 (31.2) |
1 (0.5) |
Decreased appetite |
26 (8.0) |
1 (0.3) |
12 (3.7) |
1 (0.3) |
41 (19.7) |
2 (1.0) |
Thrombocytopeniac |
18 (5.5) |
3 (0.9) |
16 (4.9) |
4 (1.2) |
38 (18.3) |
3 (1.4) |
Neutropeniac |
17 (5.2) |
7 (2.1) |
15 (4.6) |
6 (1.9) |
100 (48.1) |
41 (19.7) |
Leukopeniac |
17 (5.2) |
2 (0.6) |
15 (4.6) |
0 |
54 (26.0) |
9 (4.3) |
Rashc |
9 (2.8) |
0 |
12 (3.7) |
0 |
21 (10.1) |
3 (1.4) |
Hypercreatinemiac |
9 (2.8) |
1 (0.3) |
7 (2.2) |
0 |
45 (21.6) |
2 (1.0) |
Abbreviations: ALT = alanine aminotransferase; AST = aspartate aminotransferase; SOC ET = standard-of-care endocrine therapy; TEAE = treatment-emergent adverse event.
aIncluded 859 patients that initiated treatment.
bThe listed events are ordered according to the incidence in the imlunestrant monotherapy group. Adverse events were graded according to the Common Terminology Criteria for Adverse Events, version 5.0, of the National Cancer Institute.
cConsolidated term.
Enclosed Prescribing Information
References
The published reference below is available by contacting 1-800-LillyRx (1-800-545-5979).
1A study of imlunestrant, investigator's choice of endocrine therapy, and imlunestrant plus abemaciclib in participants with ER+, HER2- advanced breast cancer (EMBER-3). ClinicalTrials.gov identifier: NCT04975308. Updated April 8, 2025. Accessed April 25, 2025. https://clinicaltrials.gov/ct2/show/NCT04975308
2Jhaveri KL, Neven P, Casalnuovo ML, et al; EMBER-3 Study Group. Imlunestrant with or without abemaciclib in advanced breast cancer. N Engl J Med. 2025;392(12):1189-1202. https://doi.org/10.1056/NEJMoa2410858
3Jhaveri 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. Poster presented at: 47th Annual Meeting of the San Antonio Breast Cancer Symposium (SABCS); December 10-13, 2024; San Antonio, TX.
4O'Shaughnessy J, Bidard FC, Neven P, et al. Imlunestrant with or without abemaciclib in advanced breast cancer (ABC): safety analyses from the phase III EMBER-3 trial. Poster presented at: 61st Annual Meeting of the American Society of Clinical Oncology (ASCO); May 30-June 3, 2025; Chicago, IL. Accessed May 29, 2025. https://meetings.asco.org/abstracts-presentations/248581
Supplementary Material
An infographic summary of the data is also available: EMBER-3.
Date of Last Review: May 08, 2025