Imlunestrant for Early Breast Cancer

(EMBER-4 Trial)

Recruiting at 1025 trial locations

Overseen By Physicians interested in becoming principal investigators please contact

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Eli Lilly and Company

Must be taking: Endocrine therapy

Must not be taking: Tamoxifen, AIs, Raloxifene

Disqualifiers: Metastatic disease, Other cancer, 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: 5 years

8000 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests imlunestrant, a new oral treatment, to determine if it outperforms standard hormone therapies for early-stage breast cancer that is estrogen receptor positive (ER+) and HER2 negative (HER2-). The trial aims to lower the risk of cancer recurrence in individuals who have undergone hormone therapy for two to five years and face a higher-than-usual risk of recurrence. Participants should have early-stage breast cancer without evidence of metastasis and must have completed at least two years of hormone therapy. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

Do I need to stop my current medications to join the trial?

The trial information does not specify if you need to stop taking your current medications. However, since participants must have already taken endocrine therapy for two to five years, it seems likely that you may need to continue with some form of hormone therapy.

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

Research has shown that imlunestrant has been safe in previous studies. In one study, patients with advanced breast cancer found the treatment easy to handle, with the most common side effects being mild, such as tiredness and nausea.

Another study found that imlunestrant was safe and effective for patients who had tried many other treatments, suggesting the drug can be safe for people with different treatment histories.

While these studies focused on more advanced breast cancer, they provide useful information about the drug's safety. It's important to note that this trial targets early-stage breast cancer, so the experience might differ. However, the data so far shows that imlunestrant is generally well-tolerated. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Imlunestrant is unique because it is an oral treatment that offers a new way to tackle early breast cancer by targeting estrogen receptors differently. Unlike standard endocrine therapies like tamoxifen or aromatase inhibitors (anastrozole, letrozole, and exemestane), which work by blocking estrogen production or its effects, Imlunestrant is designed as an estrogen receptor degrader. This means it doesn't just block estrogen from binding but also degrades the receptor, potentially leading to more effective tumor suppression. Researchers are excited because this novel mechanism could offer better outcomes, especially for patients who have not responded well to current therapies.

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

Research shows that imlunestrant, which participants in this trial may receive, holds promise for treating certain types of breast cancer. Studies have found that it breaks down estrogen receptors and stops cancer cells from growing. In patients with specific genetic changes, imlunestrant reduced the risk of disease progression or death by 38% compared to standard treatments. It also extended the time patients lived without disease worsening, averaging 5.5 months compared to 3.8 months with standard therapies. These results suggest that imlunestrant could be a strong option for early breast cancer that is estrogen receptor positive (ER+) and HER2 negative (HER2-). Another arm of this trial involves the investigator's choice of endocrine therapy, including options like tamoxifen, anastrozole, letrozole, or exemestane. ^{1 2 3 4 6}

Who Is on the Research Team?

Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 8 AM - 8 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 people with early-stage breast cancer that's ER+ and HER2-, who've finished 2-5 years of hormone therapy but still have a high risk of the cancer coming back. They should be in good health, not have had certain other cancers or gaps in their previous treatment, and can't be pregnant or planning to become so during the study.

Inclusion Criteria

My breast cancer is early-stage, ER+ and HER2-, with no distant spread.

I have had chemotherapy or targeted therapy for my cancer.

My organs are functioning well.

Exclusion Criteria

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

I finished or stopped my hormone therapy more than 6 months ago.

Pregnant, breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the screening visit through 180 days after the last dose of study intervention.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either Imlunestrant or standard endocrine therapy

5 years

Regular visits as per protocol

Follow-up

Participants are monitored for safety and effectiveness after treatment

5 years

Long-term follow-up

Participants are monitored for overall survival and recurrence

up to 10 years

What Are the Treatments Tested in This Trial?

Interventions

• Anastrozole
• Exemestane
• Imlunestrant
• Letrozole
• Tamoxifen

Trial Overview

The trial tests Imlunestrant against standard endocrine therapies like Tamoxifen, Anastrozole, Letrozole, and Exemestane. It aims to see if Imlunestrant is more effective for those at higher risk of breast cancer recurrence after initial hormone therapy.

How Is the Trial Designed?

Group I: Imlunestrant Experimental Treatment 1 Intervention

Imlunestrant administered orally.

Group II: Investigator's Choice of Endocrine Therapy Active Control 4 Interventions

Investigator's choice of tamoxifen, anastrozole, letrozole, or exemestane administered per local approved label.

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

In a study of 25 patients with advanced ER+/HER2- breast cancer, pembrolizumab showed a modest overall response rate of 12% and a clinical benefit rate of 20%, indicating some effectiveness in this difficult-to-treat population.

The treatment was well tolerated, with 64% of patients experiencing treatment-related adverse events, primarily mild nausea and fatigue, and no treatment-related discontinuations or deaths reported.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and Antitumor Activity of Pembrolizumab in Patients with Estrogen Receptor-Positive/Human Epidermal Growth Factor Receptor 2-Negative Advanced Breast Cancer. Rugo, HS., Delord, JP., Im, SA., et al.[2022]

In a study of 126 patients with hormone receptor-positive, HER2-negative metastatic breast cancer, palbociclib combined with letrozole showed a clinical benefit rate of 30% for those with prior endocrine therapy and 26% for those with prior chemotherapy, indicating its effectiveness even after multiple treatments.

Patients who had received two or more prior lines of therapy had 6-month and 12-month progression-free survival rates of 35% and 21%, respectively, and overall survival rates of 62% at 12 months and 35% at 24 months, demonstrating that palbociclib + letrozole can provide meaningful outcomes in heavily pretreated populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment Patterns and Outcomes Associated With Palbociclib Plus Letrozole for Postmenopausal Women With HR+/HER2- Advanced Breast Cancer Enrolled in an Expanded Access Program. Brufsky, A., Mitra, D., Davis, KL., et al.[2020]

In the Phase III POTENT trial, adding S-1 to adjuvant endocrine therapy significantly improved invasive disease-free survival (iDFS) in patients with intermediate to high recurrence risk (groups 2 and 3), with reductions in iDFS events of 49% and 29%, respectively.

No benefit was observed from adding S-1 in patients with the lowest recurrence risk (group 1), indicating that S-1 may be most effective for those at greater risk of disease recurrence.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A risk-based subgroup analysis of the effect of adjuvant S-1 in estrogen receptor-positive, HER2-negative early breast cancer. Takada, M., Imoto, S., Ishida, T., et al.[2023]

In a phase II study involving 43 patients with hormone receptor positive metastatic breast cancer, adding ribociclib to maintenance endocrine therapy significantly improved progression-free survival (PFS) to a median of 12.4 months compared to 4.75 months for those receiving endocrine therapy alone.

The study also indicated a promising safety profile, with 65.1% of patients on ribociclib experiencing clinical benefits, although a notable percentage (58.1%) experienced grade 3-4 hematological adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anti-hormonal maintenance treatment with the CDK4/6 inhibitor ribociclib after 1st line chemotherapy in hormone receptor positive / HER2 negative metastatic breast cancer: A phase II trial (AMICA). Decker, T., Lüdtke-Heckenkamp, K., Melnichuk, L., et al.[2023]

The LORDSHIPS study found that a novel oral combination of dalpiciclib, pyrotinib, and letrozole showed a promising objective response rate of 66.7% in patients with HER2-positive, hormone receptor-positive metastatic breast cancer, indicating its efficacy as a treatment option.

The most common severe side effects included neutropenia and leukopenia, but the treatment demonstrated a median progression-free survival of 11.3 months, suggesting it is a viable chemotherapy-sparing option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dalpiciclib Combined With Pyrotinib and Letrozole in Women With HER2-Positive, Hormone Receptor-Positive Metastatic Breast Cancer (LORDSHIPS): A Phase Ib Study. Zhang, J., Meng, Y., Wang, B., et al.[2022]

In the phase III MONALEESA-2 study involving 668 postmenopausal women with advanced HR+ HER2- breast cancer, treatment with ribociclib plus letrozole maintained health-related quality of life (HRQoL) scores similar to those receiving placebo plus letrozole.

Patients receiving ribociclib experienced a clinically meaningful reduction in pain as early as Week 8, which was sustained up to Cycle 15, indicating that ribociclib not only improves clinical outcomes but also enhances patient-reported outcomes related to pain management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Health-related quality of life of postmenopausal women with hormone receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer treated with ribociclib + letrozole: results from MONALEESA-2. Verma, S., O'Shaughnessy, J., Burris, HA., et al.[2022]

In a study of 396 female patients with hormone receptor positive, HER2-negative metastatic breast cancer receiving CDK4 and 6 inhibitors, the most common adverse events were neutropenia, diarrhea, and fatigue, with varying frequencies depending on the specific drug used.

The study found that while the overall incidence of adverse events was lower than in clinical trials, the rates of dose reductions and treatment holds due to these events were higher, suggesting that clinicians may be actively managing side effects to help patients continue their therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real world incidence and management of adverse events in patients with HR+, HER2- metastatic breast cancer receiving CDK4 and 6 inhibitors in a United States community setting. Price, GL., Sudharshan, L., Ryan, P., et al.[2022]

CDK4/6 inhibitors combined with endocrine treatment have become the standard first-line therapy for hormone receptor-positive metastatic breast cancer, but options for patients who progress on this treatment are limited and often associated with significant side effects.

Recent clinical trials have shown promising results for new treatments, such as the AKT-inhibitor capivasertib and the oral selective estrogen receptor degrader elacestrant, which improve progression-free survival, especially in patients with specific mutations, indicating a shift towards more effective therapies post-CDK4/6 inhibition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Filling the Gap after CDK4/6 Inhibitors: Novel Endocrine and Biologic Treatment Options for Metastatic Hormone Receptor Positive Breast Cancer. Mittal, A., Molto Valiente, C., Tamimi, F., et al.[2023]

Combining luteinizing hormone-releasing hormone (LHRH) agonists with tamoxifen is effective and safe for treating premenopausal women with hormone receptor positive metastatic breast cancer, showing superiority over single-agent therapies.

The addition of targeted therapies like palbociclib to endocrine treatments can significantly prolong progression-free survival, indicating a promising approach to overcoming endocrine resistance in this patient group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Endocrine Therapy in Premenopausal Hormone Receptor Positive/Human Epidermal Growth Receptor 2 Negative Metastatic Breast Cancer: Between Guidelines and Literature. Tancredi, R., Furlanetto, J., Loibl, S.[2019]

Oral CDK4/6 inhibitors like palbociclib, ribociclib, and abemaciclib significantly improve progression-free survival by 40-45% when combined with endocrine therapy in hormone-responsive HER2-negative advanced breast cancer, particularly in post-menopausal women.

These inhibitors have varying toxicity profiles and monitoring requirements, and ongoing clinical trials are exploring their use in other breast cancer subtypes and in combination with other therapies to overcome resistance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Role of CDK4/6 Inhibitors in Breast Cancer. Murphy, CG.[2020]

In a study of 1430 patients with hormone receptor-positive, HER2-negative metastatic breast cancer, the combination of palbociclib and letrozole significantly improved progression-free survival (20.0 months) compared to letrozole alone (11.9 months).

The combination treatment also showed a trend towards better overall survival, with a 2-year survival rate of 78.3% for the palbociclib group compared to 68.0% for those on letrozole alone, indicating its effectiveness in a real-world clinical setting.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative effectiveness of first-line palbociclib plus letrozole versus letrozole alone for HR+/HER2- metastatic breast cancer in US real-world clinical practice. DeMichele, A., Cristofanilli, M., Brufsky, A., et al.[2022]

The NCIC-CTG MA.17/BIG 1-97 trial demonstrated that extending endocrine therapy with letrozole after five years of tamoxifen significantly improves disease-free survival in hormone-receptor-positive early breast cancer patients, leading to the trial's early termination due to positive results.

This study particularly highlighted the benefits of letrozole for women with node-positive disease and pre-menopausal status, establishing it as a key approach for extended adjuvant therapy in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Extended adjuvant endocrine therapy in hormone dependent breast cancer: the paradigm of the NCIC-CTG MA.17/BIG 1-97 trial. Higgins, MJ., Liedke, PE., Goss, PE.[2022]

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Results from the EMBER-2 Study - PMC - PubMed Central

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Imlunestrant monotherapy demonstrated favourable safety, pharmacokinetics, and preliminary efficacy in patients (pts) with heavily pre-treated ER+ advanced ...