Imlunestrant + Abemaciclib for Breast Cancer

(EMBER-3 Trial)

Not currently recruiting at 451 trial locations

Overseen By There may be multiple sites in this clinical trial. 1-877-CTLILLY (1-877-285-4559) or

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Eli Lilly and Company

Must be taking: Aromatase inhibitors

Must not be taking: Chemotherapy, Fulvestrant, PI3K inhibitors

Disqualifiers: Visceral crisis, Brain metastasis, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 3 years

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial evaluates the effectiveness of a new treatment, imlunestrant, for breast cancer that is estrogen receptor positive (ER+) and human epidermal receptor 2 negative (HER2-). It compares imlunestrant alone, standard hormone therapies like exemestane or fulvestrant, and a combination of imlunestrant with abemaciclib, a CDK4/6 inhibitor. The trial focuses on breast cancer that has advanced or metastasized. Individuals whose breast cancer progressed despite certain hormone therapies might be suitable candidates. Participants may remain in the study for up to five years. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants the opportunity to contribute to potentially groundbreaking treatment advancements.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, it mentions that participants should have progressed on certain treatments, which might imply changes in medication. It's best to discuss your specific situation with the trial team.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that imlunestrant, whether used alone or with abemaciclib, is safe and manageable for treating breast cancer. Studies report that patients tolerate it well and find it easy to take since it's an all-oral treatment. Even when combined with abemaciclib, imlunestrant remains safe.

Exemestane and fulvestrant, already approved and widely used for similar conditions, have well-established safety profiles. Recent studies have not identified any new safety concerns.

In summary, those considering joining this trial can be assured that past research has shown the treatments to be safe and tolerable. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about Imlunestrant and Abemaciclib for breast cancer because they offer new approaches compared to standard endocrine therapies like exemestane and fulvestrant. Imlunestrant, a novel oral selective estrogen receptor degrader (SERD), uniquely targets the estrogen receptor, potentially offering more effective inhibition of cancer growth. When combined with Abemaciclib, a CDK4/6 inhibitor, this treatment could enhance cancer cell cycle arrest, providing a potent one-two punch against tumor progression. These innovations might lead to improved outcomes for patients who need new options beyond traditional hormone treatments.

What evidence suggests that this trial's treatments could be effective for breast cancer?

In this trial, participants will receive different treatments to evaluate their effectiveness. A previous study showed that imlunestrant increased the time patients lived without cancer progression to 5.5 months, compared to 3.8 months with standard hormone therapy. This suggests that imlunestrant could be effective for individuals with certain genetic changes. In this trial, some participants will receive imlunestrant alone, while others will receive it with abemaciclib. Previous studies demonstrated that when combined with abemaciclib, imlunestrant significantly increased the time without cancer progression compared to imlunestrant alone. These findings indicate that this combination could be a strong option for treating advanced breast cancer that is estrogen receptor positive and HER2 negative. ^{3 5 6 7 8}

Who Is on the Research Team?

Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST)

Principal Investigator

Eli Lilly and Company

Are You a Good Fit for This Trial?

This trial is for postmenopausal women with advanced breast cancer that's ER+ and HER2-. They should have seen their cancer progress after aromatase inhibitor treatment, possibly combined with a CDK4/6 inhibitor. Participants must be able to take pills, have measurable disease or bone-only disease, and be in good physical condition (ECOG 0-1). They can't join if they've had certain prior treatments like chemotherapy or specific inhibitors, have severe brain metastasis, visceral crisis, lung complications from cancer spread, or serious medical conditions.

Inclusion Criteria

My breast cancer is ER+ and HER2-, and has spread beyond the breast.

My cancer progressed after treatment with an aromatase inhibitor and possibly a CDK4/6 inhibitor.

My kidney, blood, and liver functions are all within normal ranges.

Exclusion Criteria

I have previously been treated with specific cancer therapies, excluding early-stage chemotherapy.

My cancer has spread to my organs, lungs, or brain/spinal cord linings.

Have serious preexisting medical conditions that, in the judgment of the investigator, would preclude participation in this study

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive imlunestrant, investigator's choice of endocrine therapy, or imlunestrant plus abemaciclib

Up to 3 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 2 years

Open-label extension (optional)

Participants may opt into continuation of treatment long-term

Long-term

What Are the Treatments Tested in This Trial?

Interventions

• Abemaciclib
• Exemestane
• Fulvestrant
• Imlunestrant

Trial Overview The study tests the effectiveness of Imlunestrant against standard hormone therapy and combines Imlunestrant with Abemaciclib versus Imlunestrant alone in treating ER+, HER2- advanced breast cancer. The goal is to see which treatment works better for patients whose cancer has spread. Participation could last up to five years.

How Is the Trial Designed?

Group I: Arm C: Imlunestrant + Abemaciclib Experimental Treatment 2 Interventions

Participants received Imlunestrant 400 mg orally once daily on Days 1 to 28 of a 28-day cycle, plus Abemaciclib 150 mg orally twice daily on Days 1 to 28 of a 28-day cycle, until disease progression or a criterion for discontinuation was met.

Group II: Arm B: Investigator's Choice of Endocrine Therapy Experimental Treatment 2 Interventions

Participants received the investigator's choice of endocrine therapy, either exemestane 25 mg administered orally once daily on days 1 to 28 of a 28-day cycle, or Fulvestrant 500 mg intramuscularly on days 1 and 15 of Cycle 1, then on Day 1 of Cycle 2 and beyond, until disease progression or a criterion for discontinuation was met.

Group III: Arm A: Imlunestrant Experimental Treatment 1 Intervention

Participants received Imlunestrant 400 milligrams (mg) orally once daily on days 1 to 28 of a 28-day cycle, until disease progression or a criterion for discontinuation were met.

Exemestane is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Aromasin for:

• Early breast cancer
• Advanced breast cancer

Approved in United States as Aromasin for:

• Early breast cancer
• Advanced breast cancer

Approved in Canada as Aromasin for:

• Early breast cancer
• Advanced breast cancer

Approved in Japan as Aromasin for:

• Early breast cancer
• Advanced breast cancer

Who Is Running the Clinical Trial?

Eli Lilly and Company

Lead Sponsor

Trials

2,708

Recruited

3,720,000+

Dr. Daniel Skovronsky

Eli Lilly and Company

Chief Medical Officer since 2018

MD from Harvard Medical School

David A. Ricks

Eli Lilly and Company

Chief Executive Officer since 2017

BSc from Purdue University, MBA from Indiana University

Published Research Related to This Trial

Palbociclib, when combined with fulvestrant, significantly improves progression-free survival in women with hormone receptor-positive, HER2-negative advanced breast cancer, showing a median PFS of 9.5 months compared to 4.6 months with placebo, based on a study of 521 women.

The safety profile of palbociclib includes common adverse reactions such as neutropenia and infections, which were observed in over 20% of patients, confirming its known side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval of Palbociclib in Combination with Fulvestrant for the Treatment of Hormone Receptor-Positive, HER2-Negative Metastatic Breast Cancer. Walker, AJ., Wedam, S., Amiri-Kordestani, L., et al.[2022]

In the neoMONARCH study, postmenopausal women with HR+/HER2- breast cancer showed significant decreases in Ki67 expression and achieved higher rates of complete cell-cycle arrest when treated with abemaciclib alone or in combination with anastrozole compared to anastrozole alone.

The combination therapy not only inhibited cancer cell growth but also enhanced immune activation, suggesting a dual mechanism of action that could improve treatment outcomes, while the most common side effects were manageable gastrointestinal issues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Potent Cell-Cycle Inhibition and Upregulation of Immune Response with Abemaciclib and Anastrozole in neoMONARCH, Phase II Neoadjuvant Study in HR+/HER2- Breast Cancer. Hurvitz, SA., Martin, M., Press, MF., et al.[2023]

In a pooled analysis of 1152 patients from the MONARCH 2 and MONARCH 3 studies, abemaciclib combined with endocrine therapy showed a consistent improvement in progression-free survival (PFS) across all age groups, indicating its efficacy in treating HR+, HER2- advanced breast cancer regardless of age.

Older patients experienced higher rates of clinically relevant side effects, such as diarrhea and nausea, but these were manageable with dose adjustments, suggesting that while safety concerns exist, the treatment remains effective for older populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of abemaciclib plus endocrine therapy in older patients with hormone receptor-positive/human epidermal growth factor receptor 2-negative advanced breast cancer: an age-specific subgroup analysis of MONARCH 2 and 3 trials. Goetz, MP., Okera, M., Wildiers, H., et al.[2022]

Abemaciclib combined with endocrine therapy (ET) significantly improves quality-adjusted life years (QALYs) in patients with high-risk hormone receptor positive, HER2-negative early breast cancer, with an increase of 0.99 QALYs compared to ET alone.

The treatment is considered cost-effective in Italy, with an incremental cost-effectiveness ratio of €22,651 per QALY gained, and a 99% likelihood of being cost-effective at a threshold of €30,000 per QALY.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cost-effectiveness analysis of abemaciclib with endocrine therapy (ET) versus ET alone for HR+, HER2-, node-positive, high-risk early breast cancer in Italy. Davie, A., Traoré, S., Giovannitti, M., et al.[2023]

In the MONARCH 3 study involving 493 postmenopausal women with hormone receptor-positive, HER2-negative advanced breast cancer, abemaciclib combined with a nonsteroidal aromatase inhibitor significantly improved progression-free survival (PFS) to 28.18 months compared to 14.76 months for the placebo group.

The objective response rate (ORR) was also higher in the abemaciclib group at 61.0% versus 45.5% in the placebo group, with a tolerable safety profile, although some patients experienced grade ≥3 adverse events like neutropenia and diarrhea.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

MONARCH 3 final PFS: a randomized study of abemaciclib as initial therapy for advanced breast cancer. Johnston, S., Martin, M., Di Leo, A., et al.[2023]

In the FLIPPER trial, the combination of palbociclib and fulvestrant significantly improved progression-free survival (PFS) in postmenopausal women with HR+/HER2- advanced breast cancer compared to placebo and fulvestrant.

Patient-reported outcomes indicated that while global health status and quality of life (QoL) were maintained during treatment with palbociclib/fulvestrant, the time to deterioration in QoL was longer with placebo/fulvestrant, suggesting that palbociclib/fulvestrant is a beneficial treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Quality of life with palbociclib plus fulvestrant versus placebo plus fulvestrant in postmenopausal women with endocrine-sensitive hormone receptor-positive and HER2-negative advanced breast cancer: patient-reported outcomes from the FLIPPER trial. Tibau, A., Martínez, MT., Ramos, M., et al.[2023]

In a phase III study involving 493 postmenopausal women with HR-positive, HER2-negative advanced breast cancer, abemaciclib significantly improved progression-free survival compared to placebo, with a hazard ratio of 0.54, indicating a strong efficacy as initial therapy.

The most common side effect of abemaciclib was diarrhea, occurring in 81.3% of patients, but most cases were mild (grade 1), suggesting that while there are some adverse effects, the treatment has a tolerable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

MONARCH 3: Abemaciclib As Initial Therapy for Advanced Breast Cancer. Goetz, MP., Toi, M., Campone, M., et al.[2022]

Interim results from the MONARCH3 study show that abemaciclib, a CDK4/6 inhibitor, is an effective first-line treatment for advanced ER-positive, HER2-negative breast cancer.

Patients receiving abemaciclib in combination with letrozole experienced significantly improved progression-free survival compared to those receiving a placebo with endocrine therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First-Line Abemaciclib Effective in ER+ Breast Cancer. [2019]

In the MONARCH 2 study, abemaciclib combined with fulvestrant significantly improved progression-free survival (PFS) and overall survival (OS) in patients with hormone receptor positive, HER2-negative advanced breast cancer, showing consistent benefits across both first-line and second-line treatment groups.

The most substantial benefits were seen in patients with primary resistance to endocrine therapy and those with visceral disease, indicating that abemaciclib may be particularly effective for these subgroups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

MONARCH 2: Subgroup Analysis of Patients Receiving Abemaciclib Plus Fulvestrant as First-Line and Second-Line Therapy for HR+, HER2--Advanced Breast Cancer. Neven, P., Johnston, SRD., Toi, M., et al.[2022]

Citations

1. nejm.org nejm.org/doi/full/10.1056/NEJMoa2410858

Imlunestrant with or without Abemaciclib in Advanced ... Among 256 patients with ESR1 mutations, the median progression-free survival was 5.5 months with imlunestrant and 3.8 months with standard ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT04188548

NCT04188548 | A Study of LY3484356 in Participants With ... The reason for this study is to see if the study drug LY3484356 alone or in combination with other anticancer therapies is safe and effective in participants ...

3. ascopubs.org ascopubs.org/doi/10.1200/JCO.2022.40.16_suppl.1021

A phase 1a/b trial of imlunestrant (LY3484356), an oral ... Results: As of January 14, 2022, 138 patients (n = 114 aBC, n = 24 EEC) received imlunestrant monotherapy at doses ranging from 200-1200 mg QD.

4. fda.gov fda.gov/drugs/resources-information-approved-drugs/fda-approves-imlunestrant-er-positive-her2-negative-esr1-mutated-advanced-or-metastatic-breast

FDA approves imlunestrant for ER-positive, HER2-negative ... The median PFS was 5.5 months (95% CI: 3.9, 7.4) in the imlunestrant arm and 3.8 months (95% CI: 3.7, 5.5) in the investigator's choice arm ( ...

5. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39377773/

Results from the EMBER-2 Study Imlunestrant is an oral selective estrogen receptor degrader with favorable safety and preliminary efficacy in patients with advanced breast cancer.

6. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.1060

Safety analyses from the phase III EMBER-3 trial. Imlunestrant, as monotherapy or in combination with abemaciclib, provides a safe, tolerable, all-oral targeted therapy option for patients with ER+, HER2- ABC.

7. conference-correspondent.com conference-correspondent.com/highlights/asco/safety-of-imlunestrant-in-er-positive-her2-negative-advanced-breast-cancer-ember-3-trial-results

Safety of Imlunestrant in ER-Positive, HER2-Negative ... These findings support imlunestrant as a safe, tolerable, and effective all-oral targeted therapy option for patients with ER-positive, HER2-negative ABC.

8. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39241211/

Imlunestrant, an Oral Selective Estrogen Receptor ... - PubMed Imlunestrant, as monotherapy or in combination with targeted therapy, had a manageable safety profile with evidence of preliminary antitumor ...