Abemaciclib Combination Therapy for Advanced Breast Cancer

Recruiting at 18 trial locations

Age: 18+

Sex: Female

Trial Phase: Phase 1

Sponsor: Eli Lilly and Company

Must be taking: Endocrine therapy

Must not be taking: CDK4/6 inhibitors

Disqualifiers: Severe organ dysfunction, Brain metastasis, others

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

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 21

Duration: 12 months

198 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial allows participants to continue certain ongoing therapies, such as letrozole, anastrozole, tamoxifen, exemestane, trastuzumab, and endocrine therapy, depending on the specific part of the study. However, you must stop other previous breast cancer treatments at least 14 to 21 days before starting the trial, except for the ongoing therapies mentioned.

What data supports the effectiveness of the drug Abemaciclib in combination therapy for advanced breast cancer?

Research shows that Abemaciclib, when combined with endocrine therapy, significantly reduces the risk of breast cancer recurrence and improves progression-free survival in patients with hormone receptor-positive, HER2-negative advanced breast cancer. ^{1 2 3 4 5}

Is abemaciclib safe for humans?

Abemaciclib, when used in combination with endocrine therapy for breast cancer, has a tolerable safety profile, with common side effects including diarrhea, infections, and neutropenia (low white blood cell count). These side effects are generally manageable. ^{1 2 3 6 7}

What makes the drug Abemaciclib unique for treating advanced breast cancer?

Abemaciclib is unique because it is an oral medication that specifically targets and inhibits cyclin-dependent kinases 4 and 6 (CDK4/6), which are proteins involved in cell division, helping to slow down the growth of cancer cells. It is used in combination with endocrine therapy for hormone receptor-positive, HER2-negative advanced breast cancer, and has shown to improve progression-free survival and overall survival compared to endocrine therapy alone. ^{1 2 3 6 8}

What is the purpose of this trial?

This trial is testing the safety of abemaciclib when used with other treatments for patients whose breast cancer has spread. Abemaciclib helps to stop cancer cells from growing by blocking certain proteins they need. The study aims to find out if this combination is safe for patients with advanced breast 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 breast cancer that has spread, who have specific treatment histories and organ function. Participants must not have severe preexisting conditions or certain heart diseases, and should not have received some treatments like CDK4/6 inhibitors (except in Part I) or systemic chemotherapy for metastatic disease.

Inclusion Criteria

I have been treated with a nonsteroidal aromatase inhibitor for my metastatic disease and may currently be on exemestane.

My cancer progressed despite treatment with CDK4/6 inhibitors and hormone therapy.

My breast cancer is HER2 positive and has spread to other parts.

Exclusion Criteria

Have serious preexisting medical conditions that, in the judgment of the investigator, would preclude participation in this study (including interstitial lung disease (ILD), severe dyspnea at rest or requiring oxygen therapy or, history of major surgical resection involving the stomach or small bowel)

I have brain metastases treated with radiotherapy or had neurological changes within the last 14 days.

Your recent heart test showed certain abnormal results like irregular heartbeats, signs of heart problems, or a prolonged QT interval.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive abemaciclib in combination with various therapies for metastatic breast cancer

12 months

Multiple visits per cycle (21 or 28 days)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Abemaciclib
• Anastrozole
• Endocrine therapy
• Everolimus
• Exemestane
• Fulvestrant
• Letrozole
• Loperamide
• Pertuzumab
• Tamoxifen
• Trastuzumab

Trial Overview The study tests the safety of abemaciclib combined with various therapies (like letrozole, anastrozole, tamoxifen) for advanced breast cancer. It examines how well these combinations work when the cancer has spread to other body parts.

Participant Groups

Group I: LY3023414 + LY2835219 + Fulvestrant Dose Expansion Experimental Treatment 3 Interventions

LY3023414 administered orally. LY2835219 administered orally. Fulvestrant administered IM.

Group II: LY3023414 + LY2835219 + Fulvestrant Dose Escalation Experimental Treatment 3 Interventions

LY3023414 administered orally. LY2835219 administered orally. Fulvestrant administered intramuscularly (IM).

Group III: LY2835219+ Trastuzumab Dose Expansion Experimental Treatment 2 Interventions

LY2835219 administered orally. Trastuzumab administered IV infusion. This arm is closed to enrollment.

Group IV: LY2835219+ Trastuzumab Dose Escalation Experimental Treatment 2 Interventions

LY2835219 administered orally. Trastuzumab administered intravenously (IV) infusion. This arm is closed to enrollment.

Group V: LY2835219 +Trastuzumab +Pertuzumab +Loperamide Dose Escalation Experimental Treatment 4 Interventions

LY2835219 administered orally. Loperamide administered orally. Trastuzumab administered IV infusion. Pertuzumab administered IV infusion.

Group VI: LY2835219 +Trastuzumab + Pertuzumab +Loperamide Dose Expansion Experimental Treatment 5 Interventions

Hormone Receptor Negative (HR-): LY2835219 administered orally. Loperamide administered orally. Trastuzumab administered IV infusion. Pertuzumab administered IV infusion. Hormone Receptor Positive (HR+): LY2835219 administered orally. Loperamide administered orally. Trastuzumab administered IV infusion. Pertuzumab administered IV infusion. Endocrine therapy administered orally.

Group VII: LY2835219 + Tamoxifen Experimental Treatment 2 Interventions

LY2835219 administered orally. Tamoxifen administered orally. This arm is closed to enrollment.

Group VIII: LY2835219 + Letrozole Experimental Treatment 2 Interventions

LY2835219 administered orally. Letrozole administered orally. This arm is closed to enrollment.

Group IX: LY2835219 + Exemestane + Everolimus Dose Expansion Experimental Treatment 3 Interventions

LY2835219 administered orally. Exemestane administered orally. Everolimus administered orally. This arm is closed to enrollment.

Group X: LY2835219 + Exemestane + Everolimus Dose Escalation Experimental Treatment 3 Interventions

LY2835219 administered orally. Exemestane administered orally. Everolimus administered orally. This arm is closed to enrollment.

Group XI: LY2835219 + Exemestane Experimental Treatment 2 Interventions

LY2835219 administered orally. Exemestane administered orally. This arm is closed to enrollment.

Group XII: LY2835219 + Endocrine Therapy Experimental Treatment 2 Interventions

LY2835219 administered orally. Ongoing endocrine therapy administered orally.

Group XIII: LY2835219 + Anastrozole Experimental Treatment 2 Interventions

LY2835219 administered orally. Anastrozole administered orally. This arm is closed to enrollment.

Abemaciclib is already approved in United States, European Union for the following indications:

Approved in United States as Verzenio for:

• Hormone receptor-positive (HR+), human epidermal growth factor receptor 2 (HER2)-negative advanced or metastatic breast cancer
• HR+, HER2- node-positive early breast cancer

Approved in European Union as Verzenio for:

• HR+, HER2- advanced or metastatic breast cancer
• HR+, HER2- node-positive early 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

Findings from Research

In a phase III trial, abemaciclib combined with endocrine therapy significantly reduced the risk of breast cancer recurrence in patients with hormone receptor positive (HR+), HER2-negative, node-positive early breast cancer, regardless of prior chemotherapy or tumor characteristics.

The combination treatment was generally well-tolerated, with manageable side effects such as diarrhea, infections, and neutropenia, making it a valuable option for high-risk patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Abemaciclib: A Review in Early Breast Cancer with a High Risk of Recurrence. Fung, S., Blair, HA.[2023]

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]

Abemaciclib is an oral medication that inhibits cyclin-dependent kinases 4 and 6, specifically approved in the USA for treating advanced or metastatic breast cancer that is hormone receptor-positive and HER2-negative.

It is effective both as a combination therapy with fulvestrant for patients who have progressed after endocrine therapy and as a standalone treatment for those who have also undergone chemotherapy, highlighting its role in advanced cancer management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Abemaciclib: First Global Approval. Kim, ES.[2019]

A new ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method was developed to effectively monitor abemaciclib levels in patients with advanced breast cancer, showing high accuracy and precision in quantification.

This method allows for robust therapeutic drug monitoring (TDM) of abemaciclib, which can help personalize treatment and improve adherence in patients, addressing challenges in the emerging field of oral antitumor therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An UHPLC-MS/MS method for quantification of the CDK4/6 inhibitor abemaciclib in human serum. Habler, K., Vogeser, M., Teupser, D.[2022]

In a phase III trial, adding abemaciclib to adjuvant endocrine therapy significantly improved invasive disease-free survival and distant relapse-free survival in patients with hormone receptor-positive, HER2-negative, high-risk, early breast cancer.

This finding contrasts with results from a trial involving another CDK4/6 inhibitor, which did not show similar benefits, highlighting the variability in efficacy among different treatments in this class.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Abemaciclib Reigns Over Breast Cancer in MonarchE. [2021]

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]

Abemaciclib is a potent oral CDK4 and CDK6 inhibitor that effectively treats hormone receptor-positive, HER2-negative advanced or metastatic breast cancer, showing response rates between 19.7% and 59% in major clinical trials.

The drug is well-tolerated, with common side effects including diarrhea and neutropenia, and it offers the advantage of continuous dosing and potential use as a monotherapy, making it a promising option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Abemaciclib: The Newest CDK4/6 Inhibitor for the Treatment of Breast Cancer. Palumbo, A., Lau, G., Saraceni, M.[2020]

In phase III clinical trials (MONARCH 2 and MONARCH 3), abemaciclib, a CDK4 & 6 inhibitor, significantly improved progression-free survival and overall survival in women with hormone receptor positive (HR+) and HER2-negative advanced breast cancer when used in combination with endocrine therapy.

Abemaciclib demonstrated a tolerable safety profile, making it a promising treatment option for patients who have progressed after previous endocrine therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Development of CDK4 & 6 Inhibitor Abemaciclib in Breast Cancer]. Masuda, N., Saji, S., Kawaguchi, T., et al.[2021]

References

1. France pubmed.ncbi.nlm.nih.gov

Abemaciclib: A Review in Early Breast Cancer with a High Risk of Recurrence. [2023]

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

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

3. New Zealand pubmed.ncbi.nlm.nih.gov

Abemaciclib: First Global Approval. [2019]

4. Netherlands pubmed.ncbi.nlm.nih.gov

An UHPLC-MS/MS method for quantification of the CDK4/6 inhibitor abemaciclib in human serum. [2022]

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

Abemaciclib Reigns Over Breast Cancer in MonarchE. [2021]

6. Italy 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. [2023]

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

Abemaciclib: The Newest CDK4/6 Inhibitor for the Treatment of Breast Cancer. [2020]

8. Japan pubmed.ncbi.nlm.nih.gov

[Development of CDK4 & 6 Inhibitor Abemaciclib in Breast Cancer]. [2021]