Enobosarm + Abemaciclib for Breast Cancer

(VERU-024 Trial)

No longer recruiting at 33 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment combination for certain types of advanced breast cancer. Researchers aim to determine if taking enobosarm and abemaciclib (Verzenio) together is safe and effective compared to standard estrogen-blocking treatments. It targets individuals with breast cancer that is estrogen receptor positive (ER+), HER2 negative (HER2-), and androgen receptor positive (AR+), whose cancer has worsened despite previous treatments. Those who have been treated with estrogen blockers and palbociclib, but found them ineffective, might be suitable candidates. As a Phase 3 trial, this study represents the final step before FDA approval, offering access to potentially groundbreaking treatment.

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.

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

Research has shown that using enobosarm and abemaciclib together appears safe. In earlier studies, enobosarm, which targets specific cancer cells, was tested extensively and found to be well-tolerated. Abemaciclib, also known as Verzenio, is already approved for treating breast cancer, indicating a well-known safety record.

Specifically, studies found no unexpected safety problems with this combination. Patients experienced common cancer treatment side effects like tiredness and nausea, but these were manageable. Importantly, the combination did not cause severe or life-threatening side effects beyond what is typically expected in cancer treatments.

Overall, this combination has a safety record that meets current standards for cancer treatments, making it a potentially safe option for those considering joining the trial. ^{1 2 3 4 5}

Why are researchers excited about this study treatment for breast cancer?

Unlike the standard of care for metastatic breast cancer, which typically involves aromatase inhibitors or fulvestrant, the Enobosarm and Abemaciclib combination targets cancer cells in a novel way. Enobosarm is a selective androgen receptor modulator (SARM), which helps to inhibit cancer cell growth by binding to androgen receptors, a mechanism that differs from traditional hormonal therapies. Abemaciclib, on the other hand, is a CDK4/6 inhibitor that disrupts cancer cell division by targeting specific proteins involved in cell cycle progression. Researchers are excited about this combination because it offers a dual action approach, potentially enhancing effectiveness and overcoming resistance seen with current treatments.

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

Research has shown that combining enobosarm and abemaciclib may help treat certain types of breast cancer. In this trial, participants in the Enobosarm Combination Group will receive both enobosarm and abemaciclib. Enobosarm targets and activates specific proteins called androgen receptors, which can help fight cancer cells. Earlier studies found that 12.5% of patients responded to enobosarm, even after trying other treatments. Abemaciclib, when combined with hormone therapy, lowered the risk of death by 15.8% compared to hormone therapy alone. These findings suggest that this combination could be effective for certain advanced breast cancers that have not responded to other treatments. ^{1 2 3 4 5}

Who Is on the Research Team?

Barnette

Principal Investigator

Veru Inc.

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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 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 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]

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]

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]

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 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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05065411

NCT05065411 | Efficacy & Safety Evaluation of Enobosarm ... This is an open-label safety study of enobosarm 9 mg QD coadministered with a CDK 4/6 inhibitor (abemaciclib), 150 mg BID.

2. cancernetwork.com cancernetwork.com/view/randomized-multicenter-phase-3-study-to-evaluate-the-combination-of-enobosarm-and-abemaciclib-compared-with-estrogen-blocking-agent-for-the-second-line-treatment-of-ar-er-her2-metastatic-breast-cancer-in-patients-who-have-previously-received-palbociclib-and-an-estrogen-blocking-agent-combination-therapy

8 TiP Randomized, Multicenter, Phase 3 Study to Evaluate ... Enobosarm is an oral selective AR-targeting agonist that activates the AR in breast cancer. Enobosarm has an extensive clinical experience in 25 ...

3. ir.verupharma.com ir.verupharma.com/news-events/press-releases/detail/186/veru-reports-clinical-data-from-the-discontinued-artest

Veru Reports Clinical Data from the Discontinued ARTEST ... Overall response rates of 12.5% are observed in the enobosarm group in a heavily pretreated population versus no responses in the standard ...

4. cancerletter.com cancerletter.com/drugs-and-targets/20220204_9b/

Veru, Eli Lilly to evaluate enobosarm + Verzenio in phase ... Two years of adjuvant Verzenio (abemaciclib) plus endocrine therapy reduced the risk of death by 15.8% versus ET alone and resulted in sustained ...

5. clinicaltrialsarena.com clinicaltrialsarena.com/news/veru-lilly-breast-cancer/

Veru, Lilly partner for Phase III second-line breast cancer trial The Phase III trial will enrol 186 breast cancer patients to assess the safety and efficacy of enobosarm plus Verzenio. Vishnu Priya N ...