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Inluriyo ™ (imlunestrant) tablets
200 mg
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What are the efficacy and safety results for Inluriyo™ (imlunestrant) in 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 CDK4/6 inhibitor.
Content Overview
- Imlunestrant Versus SOC ET: Investigator-Assessed PFS in Patients With ESR1 Mutations
- Imlunestrant Versus SOC ET: Investigator-Assessed PFS in All Patients
- Imlunestrant + Abemaciclib Versus Imlunestrant: Investigator-Assessed PFS in All Patients
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; CDK4/6i = cyclin-dependent kinase 4 and 6 inhibitor; CFS = chemotherapy-free survival; ctDNA = circulating tumor DNA; ER+ = estrogen receptor-positive; ESR1m = estrogen receptor 1 gene mutation; GnRH = gonadotropin-releasing hormone; HER2- = human epidermal growth factor receptor 2-negative; N = total population; ORR = objective response rate; OS = overall survival; PFS = progression-free survival; PFS2 = progression-free survival 2; QD = once daily; R = randomization; SOC ET = standard-of-care endocrine therapy; TTC = time to chemotherapy; Y/N = yes/no.
a A GnRH agonist was required in men and premenopausal women.
b East Asia vs United States/European Union vs others.
c Investigator’s choice.
d Labeled dose.
e Enrollment into Arm C started with Protocol Amendment A (at which point 122 patients had been randomized across Arms A and B).
f Scans every 8 weeks for the first 12 months, then every 12 weeks.
g ESR1m status was centrally determined in baseline plasma by the Guardant 360 ctDNA assay and OncoCompass Plus assay (Burning Rock Biotech) for patients from China.
h Analysis conducted in all concurrently randomized patients.
i Defined as the time from randomization to start of first chemotherapy (censoring patients who died prior to initiation of chemotherapy).
j Defined as the time from randomization to initiation of first chemotherapy or death, whichever occurred first.
k Defined as the time from randomization to progression on the next line of therapy or death from any cause.
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 CDK4/6 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
The 3 primary endpoints of EMBER-3 are investigator-assessed progression-free survival (PFS) of
- imlunestrant monotherapy vs SOC ET in patients with ESR1m
- imlunestrant monotherapy vs SOC ET in all patients, and
- imlunestrant combined with abemaciclib vs imlunestrant in all patients.2
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 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 ESR1 mutations 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.
At an updated analysis with an additional 14 months of follow-up from the primary outcome analysis (data cutoff date: August 18, 2025), the PFS benefit of imlunestrant monotherapy was sustained in patients with ESR1m. Median PFS was 5.5 months for imlunestrant monotherapy vs 3.8 months for SOC ET (HR=0.62; 95% CI: 0.47-0.82; nominal p=.0007).5
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 outcome 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.
At an updated analysis with an additional 14 months of follow-up (data cutoff date: August 18, 2025), the PFS difference of imlunestrant monotherapy vs SOC ET in all patients remained similar, with median PFS of 5.6 months for imlunestrant monotherapy vs 5.5 months for SOC ET (HR=0.89; 95% CI: 0.75-1.05; nominal p=.1669).5
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 monotherapy 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 monotherapy 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 monotherapy 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.
At an updated analysis with an additional 14 months of follow-up (data cutoff date: August 18, 2025), the PFS benefit of imlunestrant combined with abemaciclib was significantly improved in all patients with a continued separation of the curves. Median PFS was 10.9 months for imlunestrant combined with abemaciclib vs 5.5 months for imlunestrant monotherapy (HR=0.59; 95% CI: 0.47-0.74; nominal p<.0001).5
Results: Key Secondary Efficacy Endpoints
The key secondary endpoint of EMBER-3 was overall survival (OS) compared between
- imlunestrant monotherapy and SOC ET arms in all patients
- imlunestrant monotherapy and SOC ET arms in patients with ESR1m, and
- imlunestrant monotherapy and imlunestrant combined with abemaciclib arms in all patients.2
Overall survival for each between-group comparison was tested only if the corresponding PFS endpoint was significant.2,5
At primary outcome analysis, as only 2 out of 3 PFS endpoints were met, a minimal fraction of the significance level was passed to the corresponding OS comparison of
- imlunestrant monotherapy vs SOC ET in patients with ESR1m (with a two-sided significance level of 5.5×10-6), and
- imlunestrant combined with abemaciclib vs imlunestrant in all concurrently randomized patients (with a two-sided significance level of 1.6×10-6).5
The estimated OS data at 18 months for imlunestrant monotherapy vs SOC ET in patients with ESR1m (HR=0.55; 95% CI: 0.35-0.86; p=.008 [not significant; threshold p=2.2×10-10]) and all patients (HR=0.69; 95% CI: 0.50-0.96; not inferentially tested) were immature at the time of the primary outcome analysis of EMBER-3.2
The OS data for imlunestrant combined with abemaciclib vs imlunestrant were immature (15% event rate) at the time of the primary outcome analysis of EMBER-3 (HR=1.34; 95% CI, 0.81-2.21; p=.25).2
The updated OS results from a prespecified interim OS analysis with 14 months of additional follow-up from the primary outcome analysis (data cutoff date: August 18, 2025) and trigerred by approximately 255 OS events from the imlunestrant and SOC ET arms is presented below.5
Imlunestrant Versus SOC ET: Interim Overall Survival at 50% Maturity in Patients With ESR1 Mutations
With a median follow-up of 29.5 months, 128 OS events were observed among 256 patients with ESR1m (imlunestrant, n=57 [41%] and SOC ET, n=71 [60%]) (Imlunestrant Versus SOC ET: Interim Overall Survival at 50% Maturity in Patients With ESR1 Mutations (Results From 14-Month Follow-Up Analysis)).3,5
As shown in Imlunestrant Versus SOC ET: Interim Overall Survival at 50% Maturity in Patients With ESR1 Mutations (Results From 14-Month Follow-Up Analysis), with an additional 14 months of follow-up from primary outcome analysis, a clinically meaningful OS improvement was observed with a median OS of 34.5 months for imlunestrant monotherapy and 23.1 months for SOC ET (11.4 months absolute difference; HR=0.60; 95% CI: 0.43-0.86; p=.0043), although the boundary (p=4x10-7) for significance was not achieved.3,5
Figure 5 description: The Kaplan-Meier curve displays estimates of interim overall survival at 50% maturity in patients with ESR1 mutations who received imlunestrant monotherapy or standard-of-care endocrine therapy in EMBER-3. With 57 and 71 deaths out of 138 and 118 patients, respectively, median overall survival was 34.5 months for patients in the imlunestrant monotherapy group vs 23.1 months for those in the standard-of-care endocrine therapy group. Imlunestrant monotherapy led to an approximately 11 months numerical improvement in median overall survival in patients with ESR1 mutations with a hazard ratio equal to 0.60 and a 95% confidence interval of 0.43 to 0.86 resulting in a p value equal to .0043. However, p value did not achieve prespecified threshold for significance (p equal to .0000004 at interim analysis 2).
Abbreviations: ESR1 = estrogen receptor 1; HR = hazard ratio; IA2 = interim analysis 2; No. = number; NR = not reached; SOC ET = standard-of-care endocrine therapy.
Note: The median follow-up was 29.5 months across both arms.
Data cutoff date for overall survival interim analysis 2: August 18, 2025.
Imlunestrant + Abemaciclib Versus Imlunestrant: Interim Overall Survival at 33% Maturity in All Patients
With a median follow-up of 27 months, 140 OS events were observed among all 426 patients in the combination comparison (imlunestrant combined with abemaciclib, n=64 [30%] and imlunestrant monotherapy, n=76 [36%]) (Imlunestrant + Abemaciclib Versus Imlunestrant: Interim Overall Survival at 33% Maturity in All Patients (Results From 14-Month Follow-Up Analysis)).3,5
As shown in Imlunestrant + Abemaciclib Versus Imlunestrant: Interim Overall Survival at 33% Maturity in All Patients (Results From 14-Month Follow-Up Analysis), median OS was not reached for imlunestrant combined with abemaciclib whereas it was 34.4 months for imlunestrant monotherapy in all patients. A favorable OS trend was observed for imlunestrant combined with abemaciclib (HR=0.82; 95% CI: 0.59-1.16; p=.2622). The separation of OS curve was observed at 24 months.3,5
Figure 6 description: The Kaplan-Meier curve displays estimates of interim overall survival at 33% maturity in all patients who received imlunestrant in combination with abemaciclib or imlunestrant monotherapy in EMBER-3. With 64 and 76 deaths out of 213 and 213 patients, respectively, median overall survival was not reached for patients in the imlunestrant in combination with abemaciclib group vs 34.4 months for those in the imlunestrant monotherapy group. The hazard ratio equal to 0.82 and a 95% confidence interval of 0.59 to 1.16 resulting in a p value equal to .2622, where p value did not achieve prespecified threshold for significance (p less than .0000001 at interim analysis 2).
Abbreviations: HR = hazard ratio; IA2 = interim analysis 2; No. = number; NR = not reached.
a Efficacy analyses confined to the imlunestrant population concurrently randomized to imlunestrant plus abemaciclib treatment arm. The median follow-up was 27.1 months across both arms.
Data cutoff date for overall survival interim analysis 2: August 18, 2025.
Safety and Tolerability
The safety results from the primary outcome analysis are as follows:
- 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.
- 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.
- The most frequent AEs in both imlunestrant arms were low grade, reversible, occurred early in treatment, and resulted in few treatment discontinuations.
- The incidence of venous thromboembolism, interstitial lung disease, bradycardia, dyslipidemia, and photopsia were relatively low or not observed in both imlunestrant arms.
- In general, the safety profile of imlunestrant monotherapy and imlunestrant plus abemaciclib was consistent across age groups.2,6
EMBER-3: Summary of Adverse Events (Safety Population) and EMBER-3: TEAEs Occurring in ≥10% Patients in Any Treatment Group (Safety Population) summarizes the safety profile and commonly reported AEs across the 3 treatment groups in EMBER-3 in the primary outcome analysis.
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.
Data cutoff date: June 24, 2024.
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.
Data cutoff date: June 24, 2024.
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.
Results from 14 months of additional follow-up after the primary outcome analysis (data cutoff date: August 18, 2025) showed that
- the safety profile for imlunestrant monotherapy vs SOC ET in patients with ESR1m continued to remain favorable, with no safety findings specific to oral selective estrogen receptor degraders (SERDs), such as ocular or cardiac events, and
- imlunestrant combined with abemaciclib vs imlunestrant monotherapy in all patients had a predictable safety profile with a low discontinuation rate.3
During 14 months of additional follow-up from the primary outcome analysis, the incidence of grade ≥3 AEs, treatment discontinuations, and dose reductions due to AEs was similar to the primary outcome analysis and no new safety findings were identified.5
Enclosed Prescribing Information
References
The published references below are 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 July 11, 2025. Accessed August 29, 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 with or without abemaciclib in advanced breast cancer: updated efficacy results from the phase 3 EMBER-3 trial. Oral presentation at: 48th Annual Meeting of the San Antonio Breast Cancer Symposium (SABCS); December 9-12, 2025; San Antonio, TX.
4Jhaveri 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. Oral presentation at: 47th Annual Meeting of the San Antonio Breast Cancer Symposium (SABCS); December 10-13, 2024; San Antonio, TX.
5Jhaveri KL, Neven P, Casalnuovo ML, et al. Imlunestrant with or without abemaciclib in advanced breast cancer: updated efficacy results from the phase III EMBER-3 trial. Ann Oncol. Published online December 12, 2025. https://doi.org/10.1016/j.annonc.2025.11.018
6O'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
The data is also summarized in the following infographics: EMBER-3 and EMBER-3: Updated Efficacy Results.
Date of Last Review: January 15, 2026