Abemaciclib + Tamoxifen for Metastatic Breast Cancer

(Next MONARCH 1 Trial)

Recruiting at 108 trial locations

Age: 18+

Sex: Female

Trial Phase: Phase 2

Sponsor: Eli Lilly and Company

Must not be taking: CDK4/6 inhibitors

Disqualifiers: CNS metastasis, Cardiac history, Infections, 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: Unknown

Duration: Up to 21 months

234 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

Yes, you will need to stop taking certain cancer therapies, like aromatase inhibitors, anti-estrogens, chemotherapy, radiotherapy, and immunotherapy, at least 14 to 21 days before starting the study treatment.

What data supports the effectiveness of the drug Abemaciclib combined with Tamoxifen for treating metastatic breast cancer?

Abemaciclib, when used with other endocrine therapies, has been shown to improve progression-free survival in patients with advanced ER-positive, HER2-negative breast cancer. It is effective as a first-line therapy and in cases where the disease has progressed after initial treatments. ^{1 2 3 4 5}

Is the combination of Abemaciclib and Tamoxifen safe for treating metastatic breast cancer?

Abemaciclib, when used alone or with other treatments like Tamoxifen, has shown a tolerable safety profile in treating advanced breast cancer. Common side effects include diarrhea, infections, and low white blood cell counts, but these are generally manageable. ^{1 2 3 6 7}

How is the drug combination of Abemaciclib and Tamoxifen unique for treating metastatic breast cancer?

The combination of Abemaciclib and Tamoxifen is unique because Abemaciclib is a CDK4/6 inhibitor that targets specific proteins involved in cell division, and when combined with Tamoxifen, a hormone therapy, it offers a novel approach to treating hormone receptor-positive, HER2-negative breast cancer by potentially improving progression-free survival compared to hormone therapy alone. ^{1 2 8 9 10}

What is the purpose of this trial?

The main purpose of this study is to evaluate the safety and efficacy of abemaciclib plus tamoxifen or abemaciclib alone in women with previously treated hormone receptor-positive (HR+), human epidermal growth factor receptor 2 negative (HER2-), metastatic 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 women with HR+, HER2- metastatic breast cancer who've had at least two chemotherapy regimens, one of which may have been in the metastatic setting. Participants must have recovered from previous treatments, be able to swallow pills, and not be pregnant. They should not have persistent diarrhea or other cancers unless in remission for three years.

Inclusion Criteria

My organs are functioning well.

My breast cancer is hormone receptor positive and HER2 negative.

My condition worsened after hormone therapy.

Exclusion Criteria

I have a history of fainting, irregular heartbeats, or sudden cardiac arrest.

I have been cancer-free from other types of cancer, except for nonmelanoma skin cancer or in-situ cervical or breast cancer, for at least 3 years.

I do not have an active infection requiring IV antibiotics or a detectable viral infection.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Abemaciclib plus Tamoxifen or Abemaciclib alone, administered orally every 12 hours, with treatment continuing until discontinuation criteria are met

Up to 21 months

Regular visits as per treatment cycle

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Abemaciclib
• Tamoxifen

Trial Overview The study tests the safety and effectiveness of Abemaciclib alone or combined with Tamoxifen versus standard care in women whose breast cancer has progressed after hormone therapy. The goal is to see if these drugs can help control the disease better.

Participant Groups

Group I: Abemaciclib + Tamoxifen Experimental Treatment 2 Interventions

Abemaciclib given orally every 12 hours (Q12H) in combination with tamoxifen given orally every day. Participants may continue to receive treatment until discontinuation criteria are met.

Group II: Abemaciclib + Prophylactic Loperamide Experimental Treatment 2 Interventions

Abemaciclib given orally Q12H in combination with prophylactic loperamide given orally. Participants may continue to receive treatment until discontinuation criteria are met.

Group III: Abemaciclib Experimental Treatment 1 Intervention

Abemaciclib given orally Q12H. Participants may continue to receive treatment until discontinuation criteria are met.

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]

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]

Abemaciclib, a CDK4/6 inhibitor, demonstrated single-agent activity in women with metastatic HER2-negative, ER-positive breast cancer who had previously progressed on endocrine therapy and chemotherapy, showing an objective response rate of 19.7%.

Notably, 28.2% of the responses to abemaciclib lasted at least a year, indicating potential long-term efficacy for patients with this type of breast cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Single-Agent Abemaciclib Active in Breast Cancer. [2019]

In a phase III study involving 493 postmenopausal women with HR-positive, HER2-negative advanced breast cancer, abemaciclib significantly improved progression-free survival compared to placebo, with a hazard ratio of 0.54, indicating a strong efficacy as initial therapy.

The most common side effect of abemaciclib was diarrhea, occurring in 81.3% of patients, but most cases were mild (grade 1), suggesting that while there are some adverse effects, the treatment has a tolerable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

MONARCH 3: Abemaciclib As Initial Therapy for Advanced Breast Cancer. Goetz, MP., Toi, M., Campone, M., et al.[2022]

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]

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 pooled analysis of 1152 patients from the MONARCH 2 and MONARCH 3 studies, abemaciclib combined with endocrine therapy showed a consistent improvement in progression-free survival (PFS) across all age groups, indicating its efficacy in treating HR+, HER2- advanced breast cancer regardless of age.

Older patients experienced higher rates of clinically relevant side effects, such as diarrhea and nausea, but these were manageable with dose adjustments, suggesting that while safety concerns exist, the treatment remains effective for older populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of abemaciclib plus endocrine therapy in older patients with hormone receptor-positive/human epidermal growth factor receptor 2-negative advanced breast cancer: an age-specific subgroup analysis of MONARCH 2 and 3 trials. Goetz, MP., Okera, M., Wildiers, H., et al.[2022]

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]

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. England pubmed.ncbi.nlm.nih.gov

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

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

Single-Agent Abemaciclib Active in Breast Cancer. [2019]

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

MONARCH 3: Abemaciclib As Initial Therapy for Advanced Breast Cancer. [2022]

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

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

8. Netherlands pubmed.ncbi.nlm.nih.gov

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

9. Netherlands pubmed.ncbi.nlm.nih.gov

Safety and efficacy of abemaciclib plus endocrine therapy in older patients with hormone receptor-positive/human epidermal growth factor receptor 2-negative advanced breast cancer: an age-specific subgroup analysis of MONARCH 2 and 3 trials. [2022]

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

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