Abemaciclib + Elacestrant for Brain Metastasis from Breast Cancer

(ELECTRA Trial)

Recruiting at 113 trial locations

Overseen By Mary Ann Samparani

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Stemline Therapeutics, Inc.

Must not be taking: CYP3A4 inducers/inhibitors, Herbal meds

Disqualifiers: Leptomeningeal metastases, Concurrent malignancy, others

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

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: Unknown

73 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a combination of two drugs, abemaciclib (a CDK4/6 inhibitor) and elacestrant (a selective estrogen receptor degrader), to treat breast cancer that has spread to the brain. The researchers aim to find the best dose and assess how well these drugs work together against this specific cancer type. People with ER-positive, HER-2 negative breast cancer who have active brain metastases and have previously tried certain cancer therapies might be suitable for this study. The trial involves multiple groups to determine the most effective dosage. As a Phase 1, Phase 2 trial, it focuses on understanding how the treatment works in people and measuring its effectiveness in an initial, smaller group, offering participants a chance to contribute to groundbreaking research.

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

The trial protocol does not specify if you need to stop your current medications. However, you cannot take certain medications like strong or moderate inducers or inhibitors of CYP3A4, some herbal preparations, or receive vaccinations within specific timeframes before starting the trial.

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

Research has shown that the combination of abemaciclib and elacestrant is promising in terms of safety. In a study with 26 patients, no severe side effects required stopping the medication, indicating that the treatment was generally well-tolerated.

Both drugs can reach the brain, which is crucial for treating cancer that has spread there. This suggests they can effectively target the brain without causing major problems. Ongoing research focuses on finding the best dose, so staying updated on new findings can provide more information about their safety. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of abemaciclib and elacestrant for treating brain metastasis from breast cancer because it offers a new way to tackle the disease. Unlike traditional treatments like surgery, radiation, or chemotherapy, abemaciclib is a cyclin-dependent kinase (CDK) 4/6 inhibitor that specifically targets proteins involved in cell division, which may help slow down the growth of cancer cells. Elacestrant is a selective estrogen receptor degrader (SERD), and its role is to disrupt estrogen signaling pathways, potentially reducing cancer cell proliferation. Together, this combination targets both the growth cycle and hormone receptor pathways, offering a dual approach that could be more effective than current options.

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

Research has shown that combining elacestrant and abemaciclib effectively treats advanced breast cancer that is ER-positive and HER2-negative. This treatment has either shrunk tumors or slowed their growth. In this trial, participants will receive varying dosages of elacestrant and abemaciclib to find the most effective combination. Both drugs can penetrate the brain, which is typically protected by a barrier that excludes most drugs. This ability makes the combination promising for treating cancer that has metastasized to the brain. Early results suggest this treatment could benefit patients with breast cancer that has spread to the brain. ^{1 2 3 4 6}

Are You a Good Fit for This Trial?

This trial is for men and women over 18 with brain metastases from ER-positive, HER-2 negative breast cancer. They must have had prior treatments including endocrine therapy and chemotherapy, be stable neurologically for at least 2 weeks, and not be breastfeeding or pregnant. Participants need to have good organ function and performance status, cannot have leptomeningeal metastases or imminent organ failure, and must agree to use effective contraception.

Inclusion Criteria

Your blood, bone marrow, and organ functions are within normal range, and you are able and willing to attend all study appointments and follow the study's instructions.

My cancer is ER-positive and HER-2 negative, confirmed by a test within the last 2 years.

I can take care of myself but might not be able to do heavy physical work.

Exclusion Criteria

I have not taken elacestrant or similar drugs for my cancer.

Patients currently receiving or received any of the following medications prior to first dose of trial therapy: Known strong or moderate inducers or inhibitors of cytochrome P450 (CYP) 3A4 within 21 days prior to initiating trial therapy, Herbal preparations/medications, Vaccination, including but not limited to vaccination against COVID-19, during the 7 days prior to randomization, Any severe medical or psychiatric condition that in the opinion of the investigator(s) would preclude the patient's participation in a clinical study

I have metastatic breast cancer and haven't received treatment, or it recurred within 12 months after my last treatment.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Phase 1b Treatment

Evaluation of elacestrant in combination with abemaciclib to select the recommended phase 2 dose

1 year

Regular visits for dose-limiting toxicity evaluation

Phase 2 Treatment

Ongoing evaluation of elacestrant in combination with abemaciclib at the recommended phase 2 dose

3 years

Regular visits for treatment and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

3 years

What Are the Treatments Tested in This Trial?

Interventions

• Abemaciclib
• Elacestrant

Trial Overview The study is testing the combination of two drugs: Elacestrant and Abemaciclib in patients with brain metastasis due to hormone receptor-positive (HR+)/HER2-negative breast cancer. It's an open-label global study that will first determine the best dose (Phase 1b) followed by a larger test of effectiveness (Phase 2).

How Is the Trial Designed?

Group I: Phase 2 Experimental Treatment 2 Interventions

Elacestrant in combination with abemaciclib at the RP2D determined in Phase 1b

Group II: Phase 1b Cohort 3 Experimental Treatment 2 Interventions

Elacestrant 400 mg QD + abemaciclib 150 mg BID

Group III: Phase 1b Cohort 2 Experimental Treatment 2 Interventions

Elacestrant 400 mg QD + abemaciclib 100 mg BID

Group IV: Phase 1b Cohort 1 Experimental Treatment 2 Interventions

Elacestrant 300 milligrams (mg) once daily (QD) + abemaciclib 100 mg twice daily (BID)

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?

Stemline Therapeutics, Inc.

Lead Sponsor

Trials

24

Recruited

6,500+

Stemline Therapeutics, Inc.

Lead Sponsor

Trials

24

Recruited

6,500+

Published Research Related to This Trial

In a phase II study involving patients with hormone receptor-positive metastatic breast cancer and brain or leptomeningeal metastases, abemaciclib showed an intracranial clinical benefit rate of 24% in cohort A (n=58), indicating some effectiveness in this heavily pretreated group.

Abemaciclib achieved significantly high concentrations in brain metastases tissue, exceeding the levels needed for effective inhibition of CDK4 and CDK6, suggesting potential for further exploration of this treatment in combination therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Phase II Study of Abemaciclib in Patients with Brain Metastases Secondary to Hormone Receptor-Positive Breast Cancer. Tolaney, SM., Sahebjam, S., Le Rhun, E., et al.[2021]

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 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]

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]

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]

In the phase II MONARCH 1 study involving 132 women with refractory hormone receptor-positive, HER2-negative metastatic breast cancer, abemaciclib showed a confirmed objective response rate of 19.7% and a clinical benefit rate of 42.4%, indicating promising efficacy in a heavily pretreated population.

Abemaciclib was well tolerated, with the most common side effects being diarrhea, fatigue, and nausea, and only 7.6% of patients discontinued treatment due to adverse events, suggesting a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

MONARCH 1, A Phase II Study of Abemaciclib, a CDK4 and CDK6 Inhibitor, as a Single Agent, in Patients with Refractory HR+/HER2- Metastatic Breast Cancer. Dickler, MN., Tolaney, SM., Rugo, HS., et al.[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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05386108

NCT05386108 | Study of Abemaciclib and Elacestrant in ... This is a multi-site, global, open-label study that includes a phase 1b evaluation of elacestrant in combination with abemaciclib in women and men with brain ...

2. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.1064

Elacestrant in combination with abemaciclib in patients (pts ... ELECTRA (NCT05386108) phase 1b is evaluating the safety of elacestrant + abemaciclib in pts regardless of metastases site and ESR1 status.

3. onclive.com onclive.com/view/elacestrant-plus-abemaciclib-shows-efficacy-in-er-her2-advanced-or-metastatic-breast-cancer

Elacestrant Plus Abemaciclib Shows Efficacy in ER+/HER2 Elacestrant plus abemaciclib demonstrated clinically important efficacy in ER-positive/HER2-negative advanced or metastatic breast cancer.

4. annalsofoncology.org annalsofoncology.org/article/S0923-7534(24)01831-3/fulltext

364P Elacestrant in combination with abemaciclib ... Phase 2 will evaluate the efficacy and safety of the combination in pts with brain mets as both compounds have also been shown to cross the BBB (Conlan, 2020; ...

5. targetedonc.com targetedonc.com/view/elacestrant-abemaciclib-for-er-her2--breast-cancer-promising-early-results

Elacestrant/Abemaciclib for ER+, HER2- Breast Cancer Phase 2 will look at the efficacy and safety, specifically in patients with brain metastases. Preliminary results were presented at the 2024 ...

6. asco.org asco.org/abstracts-presentations/ABSTRACT459260

Elacestrant in combination with abemaciclib in patients (pts ... Results: As of January 2024, 26 pts were enrolled in the phase 1b elacestrant + abemaciclib cohorts, none with brain metastases. No dose-limiting toxicities ...