Endocrine + CDK4/6 Inhibitor Therapy for Breast Cancer

Recruiting at 1 trial location

Overseen By Shahbano Shakeel

Age: 18+

Sex: Female

Trial Phase: Phase 2

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 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

Compensation: Varies

Number of Visits: 1

Duration: 2 weeks

60 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether combining endocrine therapy with a drug targeting specific proteins (cyclin-dependent kinase inhibitors) can enhance the immune system's ability to fight breast cancer in patients with hormone receptor-positive breast cancer. Participants will receive either a combination of two medications, Abemaciclib (a CDK4/6 inhibitor) and Letrozole, or Letrozole alone for two weeks. The study seeks women with estrogen or progesterone receptor-positive breast tumors who are planning surgery. Participants must be post-menopausal and able to swallow oral medications. As a Phase 2 trial, the 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 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.

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

Research has shown that both abemaciclib and letrozole have been studied for their safety in treating breast cancer. Abemaciclib, when combined with hormone therapies like letrozole, offers significant benefits for patients with hormone receptor-positive breast cancer. Several studies found that abemaciclib was generally well-tolerated, though some patients experienced side effects such as diarrhea, tiredness, and nausea. Most found these side effects manageable.

Letrozole is a common treatment for breast cancer and is usually well-tolerated. It has been shown to help lower the risk of cancer recurrence. Some people taking letrozole may experience side effects like hot flashes, joint pain, or tiredness.

Both treatments have been approved for use in other situations, so their safety is well-known. While side effects can occur, they are usually mild to moderate and manageable. Clinical trial participants are closely monitored to manage any side effects. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments because they involve a combination of endocrine therapy with letrozole and a CDK4/6 inhibitor called abemaciclib. Unlike traditional treatments for breast cancer that primarily focus on hormone receptors, abemaciclib targets proteins involved in cell division, specifically CDK4 and CDK6. This dual approach aims to not only reduce hormone-driven tumor growth but also directly interfere with the cancer cell cycle, potentially enhancing treatment effectiveness. Additionally, patients may benefit from the combination treatment's potential to work more quickly, showing results in just a couple of weeks.

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

This trial will compare the effectiveness of two treatment approaches for hormone receptor-positive breast cancer. Participants in Arm A will receive a combination of abemaciclib and letrozole. Research has shown that using abemaciclib with letrozole may be promising; one study found that this combination lowered the risk of death by 15.8% compared to hormone therapy alone. This suggests the combination might work better than letrozole or similar treatments used by themselves. Meanwhile, participants in Arm B will receive letrozole alone, which has also been effective in reducing the chance of breast cancer recurrence. Previous studies have shown that letrozole significantly lowered the risk of cancer returning, with 73.8% of women remaining cancer-free after 8 years. Both treatments have improved outcomes for breast cancer patients, with the combination possibly offering extra benefits. ^{6 7 8 9 10}

Who Is on the Research Team?

Sangeetha Reddy, MD

Principal Investigator

University of Texas Southwestern Medical Center

Are You a Good Fit for This Trial?

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.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• Abemaciclib
• Letrozole

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.

How Is the Trial Designed?

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+

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

Published Research Related to This Trial

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]

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]

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]

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 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]

In the nextMONARCH study involving women with endocrine-refractory HR+, HER2- metastatic breast cancer, abemaciclib showed a median progression-free survival (PFS) of 9.1 months when combined with tamoxifen, but this was not significantly better than the 7.4 months PFS with abemaciclib alone plus prophylactic loperamide.

The study found that the incidence and severity of diarrhea, a common side effect of abemaciclib, were manageable with dose adjustments and antidiarrheal medication, indicating that the treatment can be tolerated while maintaining its efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

nextMONARCH: Abemaciclib Monotherapy or Combined With Tamoxifen for Metastatic Breast Cancer. Hamilton, E., Cortes, J., Ozyilkan, O., et al.[2021]

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]

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. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11368096/

Practical Guidance on Abemaciclib in Combination with ... We provide practical guidance on the use of abemaciclib in combination with ET for HR-positive, HER2-negative, high-risk early breast cancer.

3. clinicaltrials.gov clinicaltrials.gov/study/NCT03988114

A Study of Abemaciclib (LY2835219) in Participants With ... The reason for this study is to see if the drug abemaciclib in combination with nonsteroidal aromatase inhibitors (anastrozole or letrozole) is effective in ...

4. thelancet.com thelancet.com/journals/lanepe/article/PIIS2666-7762(25)00263-7/fulltext

Prevalence and prognosis of patients with breast cancer ... ∙ et al. Review of the monarchE trial suggests no evidence to support use of adjuvant abemaciclib in women with breast cancer. Lancet Oncol. 2023; 24:589 ...

5. appliedclinicaltrialsonline.com appliedclinicaltrialsonline.com/view/verzenio-kisqali-positive-long-term-results-early-breast-cancer-trials

Verzenio and Kisqali Deliver Positive Long-Term Results ... Topline findings · Verzenio plus endocrine therapy reduced the risk of death by 15.8% versus ET alone in high-risk HR+/HER2– early breast cancer.

6. clinicaltrials.gov clinicaltrials.gov/study/NCT02057133

NCT02057133 | A Study of LY2835219 (Abemaciclib) in ... This study evaluates the safety of abemaciclib in combination therapies (letrozole, anastrozole, tamoxifen, exemestane, exemestane plus everolimus, ...

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

VERZENIO® (abemaciclib) tablets, for oral use The safety of VERZENIO was evaluated in MONARCH 1, a single-arm, open-label, multicenter study in 132 women with measurable HR-positive, HER2-negative ...

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

Abemaciclib (oral route) - Side effects & dosage For early breast cancer with anastrozole, exemestane, letrozole, or tamoxifen: Adults—At first, 150 milligrams (mg) 2 times a day for up to ...

9. 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.

10. pi.lilly.com pi.lilly.com/ca/verzenio-ca-pm.pdf

Product Monograph Including Patient Medication Information The data described below reflect exposure to. VERZENIO in 327 out of 488 patients with HR-positive, HER2-negative metastatic breast cancer who received at least ...