Abemaciclib + Fulvestrant for Breast Cancer

(postMONARCH Trial)

Not currently recruiting at 239 trial locations

Overseen By There may be multiple sites in this clinical trial. 1-877-CTLILLY (1-877-285-4559) or

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Eli Lilly and Company

Must be taking: Endocrine therapy

Must not be taking: Fulvestrant, ER-directed therapy

Disqualifiers: Visceral crisis, CNS metastasis, others

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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 22 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new combination of treatments for a specific type of breast cancer that has returned or worsened after previous therapy. The study examines whether adding abemaciclib (a CDK4/6 inhibitor) to fulvestrant can more effectively combat hormone receptor-positive (HR+), HER2-negative breast cancer. Participants are divided into two groups: one receives the combination of abemaciclib and fulvestrant, while the other receives a placebo with fulvestrant. This trial suits those with HR+, HER2- breast cancer that has progressed after CDK4/6 inhibitor and hormone therapy. Participants may be involved for up to five years, depending on treatment effectiveness. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot have received any systemic therapy between disease recurrence/progression and study screening, or prior treatment with fulvestrant or certain other therapies.

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

Research shows that the combination of abemaciclib and fulvestrant is generally well-tolerated by patients with advanced breast cancer. Earlier studies demonstrated that this combination slowed cancer progression. Common side effects include diarrhea, tiredness, and nausea, but most patients manage these with supportive care. Abemaciclib already has FDA approval for other uses, indicating its safety is well understood. For those considering joining a trial, these findings suggest that the treatment is safe and manageable for most participants. ^{1 2 3 4 5}

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

Researchers are excited about the combination of Abemaciclib and Fulvestrant for breast cancer because it offers a unique approach by combining a CDK4/6 inhibitor with hormone therapy. Abemaciclib specifically targets proteins involved in cell division, potentially slowing cancer growth more effectively than hormone therapy alone. This combination could enhance treatment efficacy and provide a new option for patients whose cancer has progressed despite standard hormone therapies.

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

This trial will compare the combination of abemaciclib with fulvestrant to a placebo with fulvestrant. Studies have shown that adding abemaciclib to fulvestrant can significantly benefit certain breast cancer patients. Research indicates that this combination extends the time patients live without their cancer worsening. Specifically, it improves progression-free survival (PFS), the period during and after treatment when the cancer does not progress. For those with hormone receptor-positive (HR+), HER2-negative breast cancer, especially after other treatments have failed, this combination has shown great promise. Overall, abemaciclib with fulvestrant provides a strong option for patients facing advanced stages of this type of breast cancer. ^{1 2 4 6 7}

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 postmenopausal women with HR+, HER2- advanced or metastatic breast cancer that worsened after treatment with CDK4/6 inhibitors and endocrine therapy. They must have good organ function, measurable disease progression, be able to take oral medication, and have a performance status of 0 or 1. Women who've had chemotherapy for metastatic breast cancer or certain other treatments are excluded.

Inclusion Criteria

I am postmenopausal.

I am fully active or restricted in physically strenuous activity but can do light work.

My kidney, blood, and liver functions are all within normal ranges.

Exclusion Criteria

I have undergone multiple treatments for my advanced or metastatic disease.

I have previously been treated with specific hormone or targeted therapies for my cancer.

I have brain metastases that are causing symptoms or have not been treated.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Abemaciclib or placebo in combination with Fulvestrant until discontinuation criteria are met

Up to 22 months

Monthly visits for drug administration and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Open-label extension (optional)

Participants may opt into continuation of treatment long-term

Long-term

What Are the Treatments Tested in This Trial?

Interventions

• Abemaciclib
• Fulvestrant
• Placebo

Trial Overview The study tests if adding abemaciclib to fulvestrant improves outcomes in patients whose breast cancer progressed after previous therapies. Participants will either receive the combination of abemaciclib plus fulvestrant or a placebo plus fulvestrant over up to five years, depending on their response.

How Is the Trial Designed?

Group I: Arm A: Abemaciclib plus Fulvestrant Experimental Treatment 2 Interventions

Abemaciclib 150 milligram (mg) administered orally twice daily (BID) on Days 1 to 28 of a 28-day cycle in combination with fulvestrant 500 mg administered intramuscularly (IM) on Days 1 and 15 of Cycle 1, then on Day 1 of Cycle 2 and beyond. Participants received treatment until discontinuation criteria were met.

Group II: Arm B: Placebo plus Fulvestrant Active Control 2 Interventions

Placebo administered orally BID on Days 1 to 28 of a 28-day cycle in combination with fulvestrant 500 mg administered IM on Days 1 and 15 of Cycle 1, then on Day 1 of Cycle 2 and beyond. Participants received treatment until discontinuation criteria were 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

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]

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 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]

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]

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]

Abemaciclib combined with endocrine therapy (ET) significantly improves quality-adjusted life years (QALYs) in patients with high-risk hormone receptor positive, HER2-negative early breast cancer, with an increase of 0.99 QALYs compared to ET alone.

The treatment is considered cost-effective in Italy, with an incremental cost-effectiveness ratio of €22,651 per QALY gained, and a 99% likelihood of being cost-effective at a threshold of €30,000 per QALY.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cost-effectiveness analysis of abemaciclib with endocrine therapy (ET) versus ET alone for HR+, HER2-, node-positive, high-risk early breast cancer in Italy. Davie, A., Traoré, S., Giovannitti, M., et al.[2023]

In the premenopausal subgroup of the MONARCH 2 trial, patients treated with abemaciclib plus fulvestrant experienced significantly improved median progression-free survival (PFS) of 28.6 months compared to 10.26 months for those receiving placebo plus fulvestrant, indicating strong efficacy in hormone receptor-positive, HER2-negative advanced breast cancer.

The safety profile of abemaciclib plus fulvestrant was consistent with previous findings, supporting its use as an effective treatment option for premenopausal patients who are resistant to endocrine therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Abemaciclib plus fulvestrant in hormone receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer in premenopausal women: subgroup analysis from the MONARCH 2 trial. Neven, P., Rugo, HS., Tolaney, SM., et al.[2021]

In the MONARCH 2 study involving 669 women with advanced breast cancer, the combination of abemaciclib and fulvestrant significantly improved progression-free survival (PFS) to a median of 16.4 months compared to 9.3 months with fulvestrant alone.

The combination therapy also achieved a higher objective response rate (ORR) of 48.1% versus 21.3% in the control group, while maintaining a tolerable safety profile, with common side effects including diarrhea and neutropenia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

MONARCH 2: Abemaciclib in Combination With Fulvestrant in Women With HR+/HER2- Advanced Breast Cancer Who Had Progressed While Receiving Endocrine Therapy. Sledge, GW., Toi, M., Neven, P., et al.[2022]

In the MONARCH 2 study, abemaciclib combined with fulvestrant significantly improved progression-free survival (PFS) and overall survival (OS) in patients with hormone receptor positive, HER2-negative advanced breast cancer, showing consistent benefits across both first-line and second-line treatment groups.

The most substantial benefits were seen in patients with primary resistance to endocrine therapy and those with visceral disease, indicating that abemaciclib may be particularly effective for these subgroups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

MONARCH 2: Subgroup Analysis of Patients Receiving Abemaciclib Plus Fulvestrant as First-Line and Second-Line Therapy for HR+, HER2--Advanced Breast Cancer. Neven, P., Johnston, SRD., Toi, M., et al.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11936477/

Abemaciclib Plus Fulvestrant in Advanced Breast Cancer After ... Abemaciclib plus ET reduces the risk of recurrence for patients with high-risk early breast cancer and improves progression-free survival (PFS) and overall ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39693591/

Results From the Phase III postMONARCH Trial Conclusion: Abemaciclib + fulvestrant significantly improved PFS after disease progression on previous CDK4/6i + ET in patients with HR+, HER2- ...

3. 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 ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT05169567

Study Details | NCT05169567 | Abemaciclib (LY2835219) ... This study will evaluate the effect of adding abemaciclib to fulvestrant for the treatment of hormone receptor-positive (HR+), human epidermal growth factor ...

5. onclive.com onclive.com/view/abemaciclib-fulvestrant-improves-pfs-across-hr-her2-advanced-breast-cancer-subgroups

Abemaciclib/Fulvestrant Improves PFS Across HR+/HER2 Abemaciclib plus fulvestrant improved PFS across subgroups in hormone receptor-positive, HER2-negative advanced breast cancer post-CDK4/6 ...

6. ascopubs.org ascopubs.org/doi/abs/10.1200/JCO-24-02086

Abemaciclib Plus Fulvestrant in Advanced Breast Cancer ... Abemaciclib + fulvestrant significantly improved PFS after disease progression on previous CDK4/6i + ET in patients with HR+, HER2– ABC, ...

7. 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 ... PFS was significantly improved with the combination of abemaciclib plus fulvestrant of 16.9 months compared with 9.3 months with fulvestrant (hazard ratio, ...