LY3484356 for Breast Cancer

(EMBER Trial)

Not currently recruiting at 128 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 1

Sponsor: Eli Lilly and Company

Must not be taking: Everolimus, Alpelisib

Disqualifiers: Infections, CNS cancer, others

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

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new drug, LY3484356, alone or with other cancer treatments, to determine its safety and effectiveness for individuals with advanced breast or endometrial cancer. Participants may receive LY3484356 with drugs such as Abemaciclib (a CDK4/6 inhibitor), Trastuzumab, or Alpelisib, depending on their specific cancer type. The trial targets those with locally advanced or metastatic ER+ breast cancer or endometrial cancer who have specific treatment histories, such as prior CDK4/6 inhibitor use or certain genetic mutations. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new drug.

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, certain prior treatments like everolimus, alpelisib, and specific HER2-directed therapies are mentioned as exclusions for some participants.

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

Research has shown that LY3484356, whether used alone or with other drugs, generally has a manageable safety profile. In earlier studies, most patients taking LY3484356 experienced mild side effects, indicating they were not severe.

For instance, when combined with Abemaciclib, patients mostly reported mild side effects, suggesting the combination is generally well-tolerated. Similarly, when combined with Alpelisib, it is usually tolerated, although Alpelisib can cause high blood sugar levels in some patients.

When LY3484356 is taken with Trastuzumab, the safety remains favorable, with no new or unexpected safety concerns reported. Adding Pertuzumab to this combination is also considered safe, as no new safety issues have been observed.

Finally, combining LY3484356 with Everolimus is considered safe based on past research, which notes that Everolimus is often used with other cancer treatments.

Overall, LY3484356, on its own or in combinations, has shown a safety profile that is mostly mild, with generally manageable side effects. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike the standard breast cancer treatments, which often include hormone therapies and chemotherapy, LY3484356 offers a novel approach by potentially targeting specific pathways in cancer cells. Researchers are excited about LY3484356 because it is designed to work in combination with other drugs like Abemaciclib, Alpelisib, and Trastuzumab, enhancing their effectiveness. This combination strategy aims to more precisely attack cancer cells, potentially reducing side effects and improving outcomes compared to traditional therapies. Moreover, LY3484356 is administered orally, providing a convenient option for patients compared to some current intravenous treatments. These innovative features give hope for more effective and patient-friendly breast cancer treatment options.

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

Research has shown that LY3484356, also known as imlunestrant, holds promise for treating breast cancer. Early studies found it helped some patients with advanced breast cancer live 5.5 months longer without disease progression, outperforming some standard treatments. This trial tests LY3484356 in various combinations. One arm evaluates LY3484356 with abemaciclib, which may extend this period further. Other arms explore LY3484356 with drugs like alpelisib and trastuzumab, suggesting effectiveness in different combinations for various breast cancer types. This treatment works by breaking down estrogen receptors, potentially stopping the growth of some cancer cells. While more research is needed, these early results offer hope for patients with advanced breast cancer. ^{2 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 adults with advanced or metastatic breast or endometrial cancer. They must be able to swallow pills, have good organ function, and provide a tissue sample. Women should not be pregnant and must use effective birth control. Those with ER+/HER2- breast cancer should have seen benefits from prior hormone therapy.

Inclusion Criteria

I can swallow pills.

I have ER+/HER2- breast cancer and responded well to hormone therapy, or I have untreated advanced breast cancer.

I am willing to provide samples of my previously collected tissue.

Exclusion Criteria

Participants must not have another serious medical condition

My brain or spinal cord cancer is stable.

I do not have uncontrolled hepatitis, tuberculosis, or HIV.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Participants receive escalating doses of LY3484356 to determine the maximum tolerated dose

21/28 day cycles

Dose Expansion

Participants receive LY3484356 alone or in combination with other anticancer therapies to evaluate safety and efficacy

Estimated up to 28 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Abemaciclib
• Alpelisib
• Aromatase Inhibitor (AI)
• Everolimus
• LY3484356
• Pertuzumab
• Trastuzumab

Trial Overview The study tests LY3484356 alone or combined with other cancer drugs (Trastuzumab, Aromatase Inhibitor, Pertuzumab, Abemaciclib, Everolimus, Alpelisib) to evaluate safety and effectiveness against advanced breast or endometrial cancers.

How Is the Trial Designed?

Group I: Part E: Dose Expansion: LY3484356 + Trastuzumab + Pertuzumab Experimental Treatment 3 Interventions

LY3484356 administered orally in combination with trastuzumab and pertuzumab administered intravenously.

Group II: Part D: Dose Expansion: LY3484356 +/- Abemaciclib Experimental Treatment 2 Interventions

LY3484356 and Abemaciclib given orally with trastuzumab administered intravenously.

Group III: Part C:Dose Expansion: LY3484356 + Trastuzumab +/- Abemaciclib Experimental Treatment 3 Interventions

LY3484356 administered orally in combination with trastuzumab intravenously with or without Abemaciclib.

Group IV: Part B: Dose Expansion: Cohort E5: LY3484356 + Alpelisib Experimental Treatment 2 Interventions

LY3484356 and alpelisib given orally.

Group V: Part B: Dose Expansion: Cohort E4: LY3484356 + Everolimus Experimental Treatment 2 Interventions

LY3484356 and everolimus given orally.

Group VI: Part B: Dose Expansion: Cohort E3: LY3484356 Experimental Treatment 1 Intervention

LY3484356 given orally.

Group VII: Part A: Dose Expansion: LY3484356 + Abemaciclib +/- AI Experimental Treatment 3 Interventions

LY3484356 and abemaciclib given orally in combination with or without Aromatase Inhibitor (AI) of physician's choice (Anastrozole, Exemestane, or Letrozole) administered orally.

Group VIII: Dose Escalation LY3484356 Experimental Treatment 1 Intervention

LY3484356 given orally.

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 phase 2 trial involving 100 patients with HER2-positive advanced breast cancer resistant to trastuzumab, the combination of pyrotinib and capecitabine showed a median progression-free survival of 11.8 months, exceeding the pre-specified efficacy boundary of 8.0 months.

The treatment resulted in a high objective response rate of 70% and a disease control rate of 87%, with manageable safety profiles, as the most common severe side effect was diarrhea in 24% of patients, and no treatment-related deaths were reported.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pyrotinib plus capecitabine for trastuzumab-resistant, HER2-positive advanced breast cancer (PICTURE): a single-arm, multicenter phase 2 trial. Cao, J., Teng, Y., Li, H., et al.[2023]

Recent advancements in the treatment of advanced-stage HR-positive, HER2-negative breast cancer, including the use of estrogen receptor down regulators and CDK4/6 inhibitors, have significantly improved patient outcomes.

The review highlights the importance of recent clinical trials that led to the approval of these new therapies in first-line treatment settings, reflecting a shift in management strategies for this common breast cancer subtype.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Current frontline endocrine treatment options for women with hormone receptor-positive, Human Epidermal Growth Factor Receptor 2 (HER2)-negative advanced-stage breast cancer. Abdel-Razeq, H.[2019]

A literature review identified that patients with advanced estrogen receptor-positive (ER+) breast cancer experience a significant burden of disease, particularly after recurrence, leading to higher healthcare costs and resource consumption, although only minor differences in survival and costs were noted based on ER status.

In evaluating second-line therapies for ER+ breast cancer, studies involving over 3800 patients showed no significant differences in efficacy or safety between various treatment options, highlighting a need for improved therapies as current options may not effectively address drug resistance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Disease burden and treatment outcomes in second-line therapy of patients with estrogen receptor-positive (ER+) advanced breast cancer: a review of the literature. Boswell, KA., Wang, X., Shah, MV., et al.[2015]

The proposed evidence-based guidelines categorize breast cancer therapies into four levels (basic, limited, enhanced, and maximal) based on their contribution to survival, quality of life, and cost, allowing for a flexible approach to treatment in resource-limited settings.

For early-stage breast cancer, basic therapies include modified radical mastectomy and endocrine therapy, while advanced stages require more intensive treatments, emphasizing the importance of early detection to improve outcomes and conserve resources.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Breast cancer in limited-resource countries: treatment and allocation of resources. Eniu, A., Carlson, RW., Aziz, Z., et al.[2022]

Citations

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

A phase 1a/b trial of imlunestrant (LY3484356), an oral ... In dose escalation, imlunestrant showed favorable safety, pharmacokinetics (PK) and preliminary efficacy in patients with ER+, HER2- aBC and ER+ ...

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. asco.org asco.org/abstracts-presentations/ABSTRACT326985

A first-in-human phase 1a/b trial of LY3484356, an oral ... Preclinically, LY3484356 shows favorable efficacy and pharmacokinetic (PK) properties, including antitumor activity in ESR1 mutants. Here we present the initial ...

4. 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 ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10854647/

Oral SERD, a Novel Endocrine Therapy for Estrogen ... Regarding 22 patients who received monotherapy, preliminary efficacy results show an ORR of 5% and a CBR of 36%. Among 13 patients who received ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT04647487

NCT04647487 | A Study of LY3484356 in Women With ... The purpose for this study is to see if the study drug, LY3484356, is safe and to determine what effects it has on breast cancer in participants with Estrogen ...

7. 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 ...

8. aacrjournals.org aacrjournals.org/cancerres/article/81/13_Supplement/1236/667183/Abstract-1236-Preclinical-characterization-of

Preclinical characterization of LY3484356, a novel, potent and ... LY3484356 demonstrated significant tumor growth inhibition and tumor regressions in wild type ESR1 breast cancer xenograft models such as MCF7, ...