Abemaciclib for Triple Negative Breast Cancer

No longer recruiting at 2 trial locations

Age: 18+

Sex: Female

Trial Phase: Phase 2

Sponsor: Mayo Clinic

Must not be taking: CDK 4/6 inhibitors

Disqualifiers: Active DVT/PE, Prior radiation, Others

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

Prior Safety Data This treatment has passed at least one previous human trial

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: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests how well a new treatment, abemaciclib, can combat triple-negative breast cancer that is surgically removable but doesn't respond well to chemotherapy, either alone or with pembrolizumab. Abemaciclib blocks certain enzymes that aid cancer cell growth. Suitable participants have breast cancer that hasn't responded to chemotherapy and appears on imaging tests after treatment. The trial involves taking abemaciclib, followed by surgery, to determine if this approach can better control the cancer. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial requires participants to stop using strong and moderate inducers or strong inhibitors of cytochrome P450 3A at least 7 days before registration. If you are taking these types of medications, you will need to stop them before joining the trial.

Is there any evidence suggesting that abemaciclib is likely to be safe for humans?

Research shows that abemaciclib, the treatment under study, has been used safely in various situations. Previous studies with breast cancer patients found abemaciclib to be generally safe. Some patients experienced side effects, but these were usually manageable. Common side effects included fatigue, diarrhea, and nausea.

Other studies reported serious side effects as rare. Although more severe, they did not occur often. Abemaciclib is already approved for use in other types of breast cancer, suggesting it is generally safe, though some side effects may occur.

Prospective trial participants should discuss potential risks and benefits with their doctor. This conversation can help clarify expectations and guide decisions about what is best for their health. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for triple negative breast cancer?

Researchers are excited about abemaciclib for triple-negative breast cancer because it targets cancer cells in a new way. Unlike standard chemotherapy, which attacks all rapidly dividing cells, abemaciclib specifically inhibits cyclin-dependent kinases 4 and 6 (CDK4/6), enzymes that are crucial for cancer cell growth. This targeted approach could mean fewer side effects and a more effective attack on cancer cells. Additionally, abemaciclib is taken orally, which can be more convenient than traditional intravenous chemotherapy. Combining it with surgery might improve outcomes by shrinking tumors before they are removed.

What evidence suggests that abemaciclib might be an effective treatment for triple negative breast cancer?

Research has shown that abemaciclib may help treat breast cancer by blocking certain enzymes that cancer cells need to grow. While it has helped some breast cancer patients live longer, studies on its use for triple negative breast cancer (TNBC) have produced mixed results. Previous research suggested limited effectiveness when used alone in previously treated TNBC. In this trial, some participants will receive abemaciclib combined with surgery, with the hope that it might work better alongside other treatments. Overall, researchers are carefully studying abemaciclib to understand its full potential in different types of breast cancer. ^{1 2 6 7 8}

Who Is on the Research Team?

Matthew P. Goetz

Principal Investigator

Mayo Clinic in Rochester

Are You a Good Fit for This Trial?

This trial is for women aged 18 or older with triple negative breast cancer that remains after chemotherapy and can be surgically removed. Participants must not be pregnant, should have completed chemo within the last 56 days, and cannot use certain drugs affecting liver enzymes. They must also provide tissue samples, swallow pills, and have no other active cancers or serious medical conditions.

Inclusion Criteria

I still have signs of cancer in my breast after chemotherapy.

I am a woman aged 18 or older.

My breast cancer is in stages 1-4, may have spread to nearby lymph nodes, but not to distant parts of the body.

Exclusion Criteria

I have had a breast biopsy for this cancer.

I have not had any other cancer within the last 3 years.

I have had a blood clot in my veins or lungs within the last year or I am currently on blood thinners for a clot.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Neoadjuvant Chemotherapy

Patients receive a neoadjuvant chemotherapy regimen, with or without pembrolizumab, to assess chemotherapy resistance.

Up to 12 weeks

Treatment with Abemaciclib

Patients receive abemaciclib orally twice daily for 14-21 days, followed by surgical resection.

3 weeks

Daily oral administration

Surgical Resection

Patients undergo standard of care surgical resection after completion of abemaciclib treatment.

1 week

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessment of CD8/FOXP3 ratio and other biomarkers.

30-60 days

What Are the Treatments Tested in This Trial?

Interventions

• Abemaciclib

Trial Overview The study tests abemaciclib's effectiveness on patients with resectable triple negative breast cancer resistant to chemotherapy. It examines if this drug can halt cancer cell growth by inhibiting specific enzymes needed for their proliferation. The trial includes surgery as part of the treatment process.

How Is the Trial Designed?

Group I: Cohort A Group 2; Cohort B Group 4 (abemaciclib, surgery) Experimental Treatment 2 Interventions

Patients receive abemaciclib PO BID on days 1-14 or days 1-21 in the absence of disease progression or unacceptable toxicity. Patients then undergo standard of care surgical resection no later than 12 weeks after the last dose of neoadjuvant chemotherapy.

Group II: Cohort A Group 1; Cohort B Group 3 (surgery) Experimental Treatment 1 Intervention

Patients undergo standard of care surgical resection.

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?

Mayo Clinic

Lead Sponsor

Trials

3,427

Recruited

3,221,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

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]

The combination of the CDK4/6 inhibitor abemaciclib and the PARP inhibitor talazoparib (TAL) showed a synergistic effect in suppressing the growth of BRCA-mutated, RB-deficient triple negative breast cancer (TNBC) cells, indicating a promising treatment strategy.

This combination therapy not only effectively inhibited cell growth but also overcame resistance to TAL by inducing cell cycle arrest and activating apoptotic pathways, suggesting it could be a viable option for patients with challenging TNBC cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Novel combination treatment of CDK 4/6 inhibitors with PARP inhibitors in triple negative breast cancer cells. Guney Eskiler, G., Ozman, Z., Haciefendi, A., et al.[2023]

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]

Triple-negative breast cancer (TNBC) is a challenging subtype with limited treatment options and a poor prognosis, often leading to a median survival of only 13 months after standard therapies fail.

The newly approved drug eribulin has demonstrated a survival benefit for patients with previously treated TNBC, highlighting the need for more effective targeted therapies and the potential of biomarker-driven approaches to improve treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Optimal strategies for the treatment of metastatic triple-negative breast cancer with currently approved agents. André, F., Zielinski, CC.[2020]

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, a CDK4/6 inhibitor, shows significant effectiveness in treating various breast cancer subtypes, particularly ER+/HER2- and ER+/HER2+, as well as some triple-negative breast cancers with intact Rb signaling, based on studies using 44 breast cancer cell lines and xenograft models.

The combination of abemaciclib with hormonal therapies or HER2-targeted treatments enhances its antitumor activity without reducing the effectiveness of either treatment, suggesting a promising strategy for improving breast cancer therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preclinical Activity of Abemaciclib Alone or in Combination with Antimitotic and Targeted Therapies in Breast Cancer. O'Brien, N., Conklin, D., Beckmann, R., et al.[2020]

The combination of the CDK4/6 inhibitor abemaciclib and the androgen receptor-targeting agent seviteronel showed synergistic effects in treating androgen receptor-positive triple-negative breast cancer (TNBC) in preclinical models, suggesting a new potential therapy for this aggressive cancer subtype.

Single-cell RNA sequencing revealed variability in androgen receptor levels among TNBC cells, indicating that targeting the androgen receptor alongside cell cycle inhibition could enhance treatment efficacy in AR-positive TNBC patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Activity of Combined Androgen Receptor Antagonism and Cell Cycle Inhibition in Androgen Receptor Positive Triple Negative Breast Cancer. Christenson, JL., O'Neill, KI., Williams, MM., et al.[2022]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39908010/

A Phase II Study of Abemaciclib for Patients with ... Abemaciclib monotherapy did not show clinical activity in patients with pretreated Rb-positive mTNBC.

2. clinicaltrials.gov clinicaltrials.gov/study/NCT03130439?term=AREA%5BBasicSearch%5D(LY2835219)&rank=10&tab=results

Study Results | Abemaciclib for Patients With ... See Delay Results Type in the Results Data ... Abemaciclib for Patients With Retinoblastoma-Positive, Triple Negative Metastatic Breast Cancer.

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11995003/

A Phase II Study of Abemaciclib for Patients with ... Abemaciclib monotherapy did not show clinical activity in patients with pretreated Rb-positive mTNBC. Translational Relevance. Advanced triple-negative breast ...

4. sciencealert.com sciencealert.com/breakthrough-breast-cancer-pill-extends-survival-in-7-year-trial

Breakthrough Breast Cancer Pill Extends Survival in 7- ... A breakthrough therapy for advanced breast cancer also works well in the early stages, allegedly improving survival outcomes for patients.

5. clinicaltrials.gov clinicaltrials.gov/study/NCT04031885

NCT04031885 | A Study of Abemaciclib (LY2835219) in ... The reason for this study is to compare the efficacy of abemaciclib, in combination with fulvestrant, to that of physician's choice of chemotherapy in women ...

6. aacrjournals.org aacrjournals.org/clincancerres/article/31/8/1427/754531/A-Phase-II-Study-of-Abemaciclib-for-Patients-with

A Phase II Study of Abemaciclib for Patients with ... Abemaciclib monotherapy did not show clinical activity in patients with pretreated Rb-positive mTNBC. Translational Relevance. Advanced triple-negative breast ...

7. prnewswire.com prnewswire.com/news-releases/lillys-verzenio-abemaciclib-prolonged-survival-in-hr-her2--high-risk-early-breast-cancer-with-two-years-of-treatment-302586849.html

Lilly's Verzenio® (abemaciclib) prolonged survival in HR+, ... In metastatic breast cancer, Verzenio has demonstrated statistically significant OS in the Phase 3 MONARCH 2 study.11 Verzenio has shown a ...

8. clinicaloncologyonline.net clinicaloncologyonline.net/article/S0936-6555(24)00059-1/abstract

Real-world Data on Safety Outcome with Treatment of ... The aim of our study was to assess the adverse event profile and tolerability of adjuvant abemaciclib/endocrine therapy in real-world clinical practice in ...