Abemaciclib + Tamoxifen for Metastatic Breast Cancer

(Next MONARCH 1 Trial)

Not currently recruiting at 132 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the safety and effectiveness of combining abemaciclib (a targeted cancer therapy) with tamoxifen, or using abemaciclib alone, for women with metastatic breast cancer that is hormone receptor-positive (HR+) and lacks human epidermal growth factor receptor 2 (HER2-). The goal is to assess the effectiveness of these treatments after other therapies have failed. Women with HR+, HER2- breast cancer who have undergone at least two rounds of chemotherapy may be suitable candidates for this trial. As a Phase 2 trial, the research focuses on evaluating the treatment's effectiveness in an initial, smaller group of participants.

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.

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

Research has shown that abemaciclib, whether used alone or with other drugs like tamoxifen, is generally well-tolerated by patients with hormone receptor-positive (HR+) and HER2-negative metastatic breast cancer. Studies have found that combining abemaciclib with tamoxifen can extend patients' lives, and no new safety issues have emerged with this combination.

For those taking abemaciclib, diarrhea commonly occurs as a side effect. Loperamide is sometimes used to manage this, but in one study, about 31% of patients still needed to adjust their abemaciclib dose due to diarrhea.

These findings suggest that while side effects like diarrhea can occur, they are manageable, and the treatments are generally safe for most people. Discussing potential side effects with a healthcare provider is important when considering participation in a clinical trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments because Abemaciclib, a CDK4/6 inhibitor, offers a new way to target cancer cell division, which is different from traditional chemotherapy. Unlike standard treatments, which often focus on directly killing cancer cells, Abemaciclib works by interrupting the cancer cell cycle, potentially leading to fewer side effects. Additionally, combining Abemaciclib with Tamoxifen, a hormonal therapy, may enhance effectiveness by attacking the cancer from multiple angles. Another innovative approach in this trial is pairing Abemaciclib with prophylactic loperamide to manage potential side effects, aiming for a better quality of life for patients during treatment.

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

This trial will evaluate the effectiveness of different treatment combinations for metastatic breast cancer. Research has shown that abemaciclib, one of the treatments in this trial, can extend patient survival. In a large study, combining abemaciclib with hormone therapy reduced the risk of death by 15.8% in patients with high-risk early breast cancer. In this trial, one arm will test abemaciclib with tamoxifen. Previous studies demonstrated that patients lived an average of 24.2 months with this combination, compared to 17.0 months with abemaciclib alone in cases where the cancer is hormone receptor-positive and HER2-negative. However, adding tamoxifen did not significantly improve other outcomes, such as the duration of cancer stability during and after treatment or the percentage of patients whose tumors shrank. Overall, abemaciclib shows promise, especially when combined with tamoxifen for this type of breast cancer. ^{1 3 6 7 8}

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 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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

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]

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 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]

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]

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 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]

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 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]

Citations

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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. 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 ...

3. onclive.com onclive.com/view/abemaciclib-plus-endocrine-therapy-provides-os-benefit-in-hr-her2-negative-breast-cancer

Abemaciclib Plus Endocrine Therapy Provides OS Benefit ... Abemaciclib plus endocrine therapy reduced death risk by 15.8% in high-risk early breast cancer patients compared to endocrine therapy alone.

4. 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 ...

5. 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 ...

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

A Phase II Study of Abemaciclib for Patients with ... Conclusions: Abemaciclib monotherapy did not show clinical activity in patients with pretreated Rb-positive mTNBC. ©2025 The Authors; Published ...

7. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.e13062

The association between age, toxicity and outcomes of ... Here, we provide real-world data on the efficacy and safety of abemaciclib treatment, focusing also on elderly pts with HR+/HER2− MBC and the ...

8. oncpracticemanagement.com oncpracticemanagement.com/special-issues/the-evolution-of-abemaciclib-clinical-trial-data-for-the-treatment-of-hr-positive-her2-negative-metastatic-breast-cancer

The Evolution of Abemaciclib Clinical Trial Data for ... This article offers an overview of abemaciclib, clinical data in HR-positive/HER-negative metastatic breast cancer treatment, optimal administration, and ...