Imlunestrant for Early Breast Cancer

(EMBER-4 Trial)

Recruiting at905 trial locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 3

Recruiting

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

Pivotal Trial (Near Approval)

Prior Safety Data

Trial Summary

What is the purpose of this trial?

This trial is testing a new medication called imlunestrant to see if it works better than standard hormone treatments for certain breast cancer patients. The study focuses on patients with early-stage breast cancer that is estrogen receptor positive and HER2 negative, who have already been on hormone therapy for a period of time and are at high risk of their cancer returning. Imlunestrant works by blocking estrogen from helping cancer cells grow.

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.

What data supports the effectiveness of the drug Imlunestrant for early breast cancer?

The research highlights the effectiveness of combining endocrine therapies, like aromatase inhibitors and tamoxifen, with other treatments in hormone receptor-positive breast cancer. While Imlunestrant is not directly mentioned, similar drugs have shown improved outcomes when used in combination with other therapies, suggesting potential benefits for Imlunestrant in early breast cancer. ^{1 2 3 4 5}

What safety data exists for Imlunestrant and related treatments in humans?

The research articles provided do not contain specific safety data for Imlunestrant or its related treatments like Anastrozole, Exemestane, Letrozole, or Tamoxifen in humans. ^{1 6 7 8 9}

What makes the drug Imlunestrant unique for early breast cancer treatment?

Imlunestrant is a novel drug being studied for early breast cancer, and it may offer a new approach compared to existing treatments by targeting estrogen receptors in a different way. Unlike current standard treatments that often combine endocrine therapy with CDK4/6 inhibitors, Imlunestrant could provide an alternative for patients who have progressed on these therapies. ^{1 2 10 11 12}

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

Eligibility Criteria

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.

Trial Timeline

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

Treatment Details

Interventions

• Anastrozole (Aromatase Inhibitor)
• Exemestane (Aromatase Inhibitor)
• Imlunestrant (Selective Estrogen Receptor Downregulator (SERD))
• Letrozole (Aromatase Inhibitor)
• Tamoxifen (Selective Estrogen Receptor Modulator (SERM))

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.

Participant Groups

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

Findings from Research

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]

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]

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]

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]

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]

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]

References

1. United States pubmed.ncbi.nlm.nih.gov

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

2. England 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. [2022]

3. England 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. [2019]

4. United States 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. [2020]

5. Netherlands 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. [2023]

6. Netherlands 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. [2022]

7. England 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. [2022]

8. Netherlands 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. [2022]

9. United States 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. [2022]

10. Netherlands 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). [2023]

11. Switzerland 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. [2022]

12. Switzerland 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. [2023]