Enobosarm + Abemaciclib for Breast Cancer

(VERU-024 Trial)

Recruiting at 32 trial locations

Overseen By Barnette

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Veru Inc.

Must be taking: CDK 4/6 inhibitors

Must not be taking: Testosterone, Estrogens

Disqualifiers: CNS metastases, Severe renal impairment, 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

5 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial tests a combination of enobosarm and abemaciclib for patients with a specific type of breast cancer that has not responded to previous treatments. Enobosarm targets proteins in cancer cells to stop their growth, and abemaciclib prevents the cells from multiplying.

Do I need to stop my current medications to join the trial?

The trial protocol does not specify if you need to stop all current medications, but it does mention a 30-day washout period for certain hormone therapies and testosterone-like agents. It's best to discuss your specific medications with the trial team to understand any necessary changes.

What data supports the effectiveness of the drug Abemaciclib for breast cancer?

Research shows that Abemaciclib, when combined with endocrine therapy, is effective in treating certain types of breast cancer. It helps improve progression-free survival and reduces the risk of cancer recurrence in patients with hormone receptor positive (HR+), HER2-negative breast cancer. ^{1 2 3 4 5}

What safety data exists for Abemaciclib in humans?

Abemaciclib has been studied in breast cancer patients and is generally considered safe, with common side effects including diarrhea, infections, and low white blood cell counts (neutropenia). These side effects are usually manageable. ^{1 2 3 6 7}

What makes the drug combination of Enobosarm and Abemaciclib unique for breast cancer treatment?

The combination of Enobosarm and Abemaciclib is unique because Abemaciclib is a CDK4/6 inhibitor that, when combined with endocrine therapy, has shown to significantly improve outcomes in hormone receptor-positive, HER2-negative breast cancer, especially in high-risk early and advanced stages. This combination may offer a novel approach by potentially enhancing the effectiveness of existing therapies. ^{1 2 3 5 8}

Research Team

Barnette

Principal Investigator

Veru Inc.

Eligibility Criteria

This trial is for adults with ER+HER2- metastatic breast cancer that worsened after certain treatments. Participants must be able to consent, communicate with researchers, and meet menopausal status criteria. Women of childbearing potential and men must agree to use contraception. They should have an ECOG performance status ≤2, measurable disease per RECIST 1.1, AR% nuclei staining ≥40%, and adequate organ function.

Inclusion Criteria

Willingness to comply with the requirements of the protocol through the end of the study

Recovery from acute effects of chemotherapy and radiotherapy

Ability to swallow oral medications

Exclusion Criteria

You have a tube in your bile duct.

Your ECG shows abnormal results that could put you at higher risk.

You have a history of certain heart conditions.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Stage 1: Safety Evaluation

Open-label safety study of enobosarm 9 mg QD coadministered with abemaciclib 150 mg BID

Until disease progression

Stage 2: Efficacy and Safety Study

Multicenter, randomized, open-label study comparing Enobosarm Combination Group versus Control Treatment Group

Until disease progression

Follow-up

Safety follow-up visit approximately 30 days after last dose of study drug

30 days

Long-term Survival Follow-up

Monitoring every 30 days after last dose of study drug for 1 year, then every 90 days thereafter

1 year and then every 90 days

Treatment Details

Interventions

• Abemaciclib
• Enobosarm

Trial Overview The study tests the safety and effectiveness of Enobosarm (9 mg daily) combined with Abemaciclib (150 mg twice daily) against standard Estrogen Blocking Agents in patients who've seen their cancer progress on previous estrogen blockers plus palbociclib. The goal is to compare progression-free survival times between the two groups.

Participant Groups

Group I: Enobosarm Combination Group Experimental Treatment 1 Intervention

Enobosarm Combination Group will receive enobosarm 9 mg each day by mouth (QD), and abemaciclib will administered by mouth at a dose of 150 mg BID. Stage 2 Subjects in the Enobosarm Combination Group will receive enobosarm 9 mg QD each day by mouth and abemaciclib 150 mg BID by mouth until disease progression is observed and confirmed by BICR.

Group II: Control Treatment Group Active Control 1 Intervention

Control Treatment Group will receive a non-steroidal AI, a non-steroidal or steroidal (exemestane with or without everolimus), AI OR fulvestrant approved for the treatment of metastatic breast cancer and is part of the standard of care at the clinical study site until disease progression is observed and confirmed by BICR. The decision of which comparator treatment will be used will be made prior to randomization.

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?

Veru Inc.

Lead Sponsor

Trials

11

Recruited

750+

Findings from Research

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]

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]

The monarchE study focused on patients with high-risk HR+, HER2- early breast cancer, showing that adjuvant treatment with abemaciclib plus endocrine therapy (ET) significantly benefits these patients.

This evidence supports the use of abemaciclib in routine clinical practice for patients identified with high-risk features, potentially improving outcomes for those at risk of cancer recurrence.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adjuvant Abemaciclib Combined with Endocrine Therapy: Efficacy Results in monarchE Cohort 1. Toi, M., Boyle, F., Im, YH., et al.[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]

In a study involving 101 Japanese patients with advanced breast cancer, abemaciclib was found to be well tolerated, with all patients experiencing at least one treatment-emergent adverse event (TEAE), primarily manageable with interventions.

Common TEAEs included diarrhea (95.0% of patients), neutropenia (75.2%), and increased liver enzymes (ALT and AST), with most severe cases occurring early in treatment and effectively managed through dose adjustments and medications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety in Japanese Advanced Breast Cancer Patients Who Received Abemaciclib in MONARCH 2 and MONARCH 3: Assessment of Treatment-Emergent Neutropenia, Diarrhea, and Increased Alanine Aminotransferase and Aspartate Aminotransferase Levels. Masuda, N., Chen, Y., Kawaguchi, T., et al.[2022]

In a retrospective study of 69 female patients with hormone receptor-positive, HER2-negative metastatic breast cancer, abemaciclib demonstrated effectiveness as both a monotherapy and in combination with endocrine therapy, aligning with previous clinical trial results.

The median duration of abemaciclib treatment was 7.7 months, with 86% of patients discontinuing treatment mainly due to disease progression, indicating that while effective, the drug is often used in heavily pretreated patients with advanced disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Observational study of HR+/HER2- metastatic breast cancer patients treated with abemaciclib in Spain in the Named Patient Use Program (AbemusS). Blanch, S., Gil-Gil, JM., Arumí, M., et al.[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]

References

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

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

2. France pubmed.ncbi.nlm.nih.gov

Abemaciclib: A Review in Early Breast Cancer with a High Risk of Recurrence. [2023]

3. Italy 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. [2023]

4. England pubmed.ncbi.nlm.nih.gov

Adjuvant Abemaciclib Combined with Endocrine Therapy: Efficacy Results in monarchE Cohort 1. [2023]

5. England pubmed.ncbi.nlm.nih.gov

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

6. New Zealand pubmed.ncbi.nlm.nih.gov

Safety in Japanese Advanced Breast Cancer Patients Who Received Abemaciclib in MONARCH 2 and MONARCH 3: Assessment of Treatment-Emergent Neutropenia, Diarrhea, and Increased Alanine Aminotransferase and Aspartate Aminotransferase Levels. [2022]

7. Italy pubmed.ncbi.nlm.nih.gov

Observational study of HR+/HER2- metastatic breast cancer patients treated with abemaciclib in Spain in the Named Patient Use Program (AbemusS). [2023]

8. 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]