Endocrine + CDK4/6 Inhibitor Therapy for Breast Cancer

Recruiting at1 trial location

Overseen by Sangeetha Reddy, MD

Age: 18+

Sex: Female

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: University of Texas Southwestern Medical Center

Must be taking: Endocrine therapy

Must not be taking: Chemotherapy, Radiotherapy

Disqualifiers: Metastatic cancer, Severe illness, others

No Placebo Group

Prior Safety Data

Breakthrough Therapy

Trial Summary

What is the purpose of this trial?

This trial is studying if hormone therapy and a drug that stops cell growth can improve the immune system's response against hormone-sensitive breast cancer.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, if you are taking tamoxifen or raloxifene, you must stop at least 28 days before joining the study.

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

Research shows that adding Abemaciclib to endocrine therapy significantly reduces the risk of breast cancer recurrence and improves progression-free survival in patients with hormone receptor-positive, HER2-negative breast cancer. This combination is especially beneficial for patients with a high risk of recurrence or advanced disease. ^{1 2 3 4 5}

Is the combination of Abemaciclib and endocrine therapy safe for breast cancer patients?

The combination of Abemaciclib and endocrine therapy is generally considered safe for breast cancer patients, with common side effects including diarrhea, infections, and neutropenia (low white blood cell count). These side effects are usually manageable. ^{1 2 3 4 6}

How does the drug abemaciclib differ from other treatments for breast cancer?

Abemaciclib is unique because it is a CDK4/6 inhibitor that, when combined with endocrine therapy, specifically targets hormone receptor-positive, HER2-negative breast cancer, improving progression-free survival and overall survival compared to endocrine therapy alone. It is administered on a continuous dosing schedule and is effective in both early and advanced stages of breast cancer, making it a valuable option for patients with a high risk of recurrence. ^{1 2 3 4 7}

Research Team

Sangeetha Reddy, MD

Principal Investigator

University of Texas Southwestern Medical Center

Eligibility Criteria

This trial is for post-menopausal women with hormone receptor positive, HER2 negative breast cancer that's operable and not yet treated. They must have good organ function, be able to take oral meds, and agree to use effective contraception. Excluded are those with dementia, uncontrolled illnesses, ongoing infections or heart issues, prior treatment for current breast cancer diagnosis, active metastatic disease or severe allergies to study drugs.

Inclusion Criteria

My breast tumor is at least 1cm big and can be biopsied before and after treatment.

I stopped hormone replacement therapy at least a week ago.

I am post-menopausal, either by age, lack of menstruation for 12 months, or hormone levels.

Exclusion Criteria

My breast cancer has spread, is inflammatory, or has come back in the same area.

I am currently receiving treatment for breast cancer.

You have a condition that makes it hard for you to understand or make decisions about participating in the study, such as dementia or severe mental illness.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Abemaciclib and Letrozole or Letrozole only for 2 weeks

2 weeks

1 visit (in-person) for biopsy and blood draw

Follow-up

Participants are monitored for changes in T cell activation after treatment

2 weeks

Treatment Details

Interventions

• Abemaciclib (Cyclin Dependent Kinase Inhibitor)
• Letrozole (Hormone Therapy)

Trial Overview The study tests if the immune response against breast cancer can be improved using endocrine therapy (Letrozole) combined with a cyclin dependent kinase inhibitor (Abemaciclib). Tumor tissue and blood samples will be collected before and after two weeks of this combination treatment to analyze the effects.

Participant Groups

Group I: Arm B: Letrozole Experimental Treatment 1 Intervention

Patient will take daily letrozole only (Arm B) according to treatment arm for 2 weeks prior to your planned standard treatment for breast cancer. In addition to tests and procedures that are part of your standard care, you will have a biopsy and blood draw for study purposes prior to starting study treatment.

Group II: Arm A: Abemaciclib + Letrozole Experimental Treatment 2 Interventions

Patient will take twice daily abemaciclib and daily letrozole (Arm A) for 2 weeks prior to your planned standard treatment for breast cancer. In addition to tests and procedures that are part of your standard care, you will have a biopsy and blood draw for study purposes prior to starting study treatment.

Who Is Running the Clinical Trial?

University of Texas Southwestern Medical Center

Lead Sponsor

Trials

1,102

Recruited

1,077,000+

Daniel K. Podolsky

University of Texas Southwestern Medical Center

Chief Executive Officer since 2008

MD from Harvard Medical School

Robert L. Bass

University of Texas Southwestern Medical Center

Chief Medical Officer since 2019

MD from University of Texas Southwestern Medical School

Cancer Prevention Research Institute of Texas

Collaborator

Trials

55

Recruited

98,900+

Eli Lilly and Company

Industry 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]

The addition of CDK4 and 6 inhibitors (like abemaciclib, palbociclib, or ribociclib) to endocrine therapy significantly improves progression-free survival and response rates in patients with HR+ and HER2- metastatic breast cancer, establishing these inhibitors as a new standard of care.

Exploratory analyses suggest that abemaciclib may be particularly beneficial for women with poor prognosis indicators, although further confirmation is needed for these findings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Abemaciclib, a CDK4 and CDK6 inhibitor for the treatment of metastatic breast cancer. Martin, M., Garcia-Saenz, JA., Manso, L., et al.[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]

In a Phase 1b study involving 67 women with hormone receptor positive (HR+) and HER2 negative metastatic breast cancer, abemaciclib combined with endocrine therapies showed a median progression-free survival of 25.4 months and an objective response rate of 38.9%.

The treatment was generally well-tolerated, with manageable side effects such as diarrhea and fatigue, and no significant impact on the pharmacokinetics of the endocrine therapies used.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Abemaciclib in Combination With Endocrine Therapy for Patients With Hormone Receptor-Positive, HER2-Negative Metastatic Breast Cancer: A Phase 1b Study. Tolaney, SM., Beeram, M., Beck, JT., et al.[2022]

In a combined analysis of the MONARCH 2 and 3 trials involving women with HR+, HER2- advanced breast cancer, it was found that patients with poor prognostic factors, such as liver metastases and high-grade tumors, experienced the greatest benefit from adding abemaciclib to their treatment regimen.

The study identified key prognostic factors that can help determine when to initiate abemaciclib, showing that while patients with good prognostic factors had longer progression-free survival with endocrine therapy alone, those with poor prognostic indicators gained significant improvements in outcomes with the addition of abemaciclib.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prognostic characteristics in hormone receptor-positive advanced breast cancer and characterization of abemaciclib efficacy. Di Leo, A., O'Shaughnessy, J., Sledge, GW., et al.[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. England pubmed.ncbi.nlm.nih.gov

Abemaciclib, a CDK4 and CDK6 inhibitor for the treatment of metastatic breast cancer. [2021]

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

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

4. Switzerland pubmed.ncbi.nlm.nih.gov

Abemaciclib in Combination With Endocrine Therapy for Patients With Hormone Receptor-Positive, HER2-Negative Metastatic Breast Cancer: A Phase 1b Study. [2022]

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

Prognostic characteristics in hormone receptor-positive advanced breast cancer and characterization of abemaciclib efficacy. [2020]

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

nextMONARCH: Abemaciclib Monotherapy or Combined With Tamoxifen for Metastatic Breast Cancer. [2021]

7. Japan pubmed.ncbi.nlm.nih.gov

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