Abemaciclib Combination Therapy for Advanced Breast Cancer

Not currently 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the safety of combining abemaciclib, a cancer treatment, with various other therapies for breast cancer that has spread to other parts of the body. Researchers aim to evaluate the effectiveness of these combinations and patient tolerance. Individuals with hormone receptor-positive or HER2-positive metastatic breast cancer currently undergoing specific treatments may qualify. This trial offers an opportunity for those who have not found success with other medications for their metastatic breast cancer. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, allowing participants to be among the first to receive this new combination therapy.

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.

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

Research has shown that abemaciclib, when used with other treatments for advanced breast cancer, is generally well-tolerated. For instance, combining it with drugs like exemestane and everolimus results in expected and manageable side effects. Common side effects include diarrhea and fatigue, which can often be controlled by adjusting the dose or using additional medications.

When paired with anastrozole, abemaciclib has demonstrated significant benefits in treating advanced breast cancer, with side effects similar to those in other combinations. With tamoxifen, side effects such as nausea and fatigue are also manageable.

Studies involving abemaciclib, fulvestrant, and LY3023414 found the combination to be safe, with predictable side effects. When combined with trastuzumab, there was a slightly higher risk of diarrhea and increased liver enzymes, but these were generally manageable.

Overall, while side effects exist, they are usually known and manageable. The FDA has approved abemaciclib for use in other settings, indicating a level of safety confidence. Participants should still consult their healthcare provider about potential risks and benefits to understand how these might apply to their specific situation. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Abemaciclib combination therapies are unique because they target cancer cell growth differently from standard treatments like hormone therapies or chemotherapy. These therapies include Abemaciclib, a CDK4/6 inhibitor, which stops cancer cells from dividing by interrupting their cell cycle, offering a novel approach compared to traditional hormone therapies like Tamoxifen or chemotherapy drugs. Researchers are excited about these combinations as they have the potential to be more effective, especially in hormone receptor-positive breast cancers, by using multiple mechanisms to attack tumor growth. Additionally, the combination with drugs like Fulvestrant or Trastuzumab offers a tailored approach, potentially improving outcomes for patients with advanced breast cancer.

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

Previous studies have shown promising results for abemaciclib when combined with other treatments for hormone receptor-positive, HER2-negative advanced breast cancer. In this trial, participants may receive abemaciclib alongside treatments such as anastrozole, tamoxifen, letrozole, or exemestane. Specifically, when combined with anastrozole, abemaciclib extended patient survival by 12.6 months. With tamoxifen, it increased average survival to 24.2 months, compared to 17.0 months with abemaciclib alone. Combining abemaciclib with other hormone therapies like letrozole and exemestane has also significantly extended survival. These findings suggest that abemaciclib, when used with other treatments, can effectively slow cancer progression and extend the lives of patients with advanced breast cancer. ^{4 6 7 8 9}

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 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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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 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]

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 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]

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]

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]

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]

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]

Citations

1.

sciencedirect.com

sciencedirect.com/science/article/pii/S0960977625006149

Metastatic Breast Cancer: A Propensity-Matched ...

In this large, real-world cohort study, first-line abemaciclib was associated with a significant overall survival benefit compared to ...

2.

clinicaltrials.gov

clinicaltrials.gov/study/NCT02763566

NCT02763566 | A Study of Abemaciclib (LY2835219) in ...

The main purpose of this study is to evaluate the efficacy of the study drug abemaciclib in postmenopausal women with hormone receptor-positive (HR+), human ...

3.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC11940718/

Real-World Analysis of Adherence to Abemaciclib and ...

Results: The abemaciclib pharmacy claims of 100 women with HR+/HER2− breast cancer were retrieved. Most patients (91%) were treated in the ...

4.

ascopubs.org

ascopubs.org/doi/10.1200/JCO.23.01994

Results From a Preplanned monarchE Overall Survival ...

Two years of adjuvant abemaciclib combined with endocrine therapy (ET) resulted in a significant improvement in invasive disease-free survival (IDFS) and ...

5.

breastcancer.org

breastcancer.org/research-news/verzenio-plus-aromatase-inhibitor-improves-survival-in-advanced-stage-hormone-receptor-positive-her2-negative-breast-cancer

Verzenio Plus Aromatase Inhibitor Improves Survival in ...

The latest results from the MONARCH 3 study show that adding Verzenio to an aromatase inhibitor improves overall survival by 12.6 months.

6.

accessdata.fda.gov

accessdata.fda.gov/drugsatfda_docs/label/2021/208716s006s007s008lbl.pdf

VERZENIO® (abemaciclib) tablets, for oral use

For advanced or metastatic breast cancer, continue treatment until disease progression or unacceptable toxicity. VERZENIO may be taken with or without food [see ...

7.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC7990838/

Safety and efficacy of abemaciclib plus endocrine therapy ...

Abemaciclib in combination with endocrine therapy (ET) has demonstrated significant efficacy benefits in HR+ , HER2− advanced breast cancer patients.

8.

mayoclinic.org

mayoclinic.org/drugs-supplements/abemaciclib-oral-route/description/drg-20406567

Abemaciclib (oral route) - Side effects & dosage

Abemaciclib is used together with tamoxifen or an aromatase inhibitor (eg, anastrozole, exemestane, letrozole) to treat hormone receptor (HR)-positive, HER-2 ...

9.

oncologynewscentral.com

oncologynewscentral.com/drugs/monograph/174190-317058/abemaciclib-oral

Abemaciclib: uses, dosing, warnings, adverse events, ...

Abemaciclib is used in combination with fulvestrant for the treatment of hormone receptor-positive, HER2-negative advanced or metastatic breast cancer in adults ...