LY3484356 for Breast Cancer

(EMBER Trial)

Recruiting at 121 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

500 Participants Needed

Trial Summary

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.

What evidence supports the effectiveness of the drug LY3484356 for breast cancer?

The introduction of CDK4/6 inhibitors like abemaciclib has shown significant improvement in treatment outcomes for advanced-stage hormone receptor-positive breast cancer, suggesting potential effectiveness when combined with other therapies. ^{1 2 3 4 5}

What is the purpose of this trial?

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 with advanced or metastatic breast cancer or endometrial cancer.

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 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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

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]

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]

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]

References

1. England pubmed.ncbi.nlm.nih.gov

Pyrotinib plus capecitabine for trastuzumab-resistant, HER2-positive advanced breast cancer (PICTURE): a single-arm, multicenter phase 2 trial. [2023]

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

Breast cancer in limited-resource countries: treatment and allocation of resources. [2022]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Neoadjuvant Pyrotinib plus Trastuzumab, Docetaxel, and Carboplatin in Early or Locally Advanced Human Epidermal Receptor 2-Positive Breast Cancer in China: A Multicenter, Randomized, Double-Blind, Placebo-Controlled Phase 2 Trial. [2023]

4. Netherlands 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. [2015]

5. Saudi Arabia 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. [2019]