Lasofoxifene and Abemaciclib vs Fulvestrant and Abemaciclib for Breast Cancer

(ELAINEIII Trial)

Recruiting at 191 trial locations

Overseen By Sermonix Pharmaceuticals Study Inquiry

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Sermonix Pharmaceuticals Inc.

Must not be taking: CYP3A4 inhibitors, CYP3A4 inducers

Disqualifiers: Lung disease, QTc syndrome, Thrombophilia, 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: Approximately 3 years

500 Participants Needed

Trial Summary

What is the purpose of this trial?

The goal of this clinical trial is to assess the efficacy, safety and tolerability of the combination of lasofoxifene and abemaciclib compared to fulvestrant and abemaciclib for the treatment of pre- and postmenopausal women and men who have previously received ribociclib or palbociclib-based treatment and have locally advanced or metastatic estrogen receptor positive (ER+)/human epidermal growth factor 2 negative (HER2-) breast cancer with an estrogen receptor 1 (ESR1) mutation. The main question the study aims to answer is: • To compare the efficacy of the combination of lasofoxifene and abemaciclib with that of fulvestrant and abemaciclib Participants will receive either receive 5 mg/d of oral lasofoxifene plus oral abemaciclib 150 mg twice a day or the combination of fulvestrant 500 mg intramuscular (IM) on Days 1, 15, and 29 and then once monthly thereafter plus oral abemaciclib 150 mg twice a day.

Do I have to stop taking my current medications for this trial?

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot participate if you are on strong CYP3A4 inhibitors or inducers, as these can affect how the trial drugs work.

What data supports the effectiveness of the drug combination of Lasofoxifene and Abemaciclib vs Fulvestrant and Abemaciclib for breast cancer?

Research shows that Abemaciclib, when combined with endocrine therapy like Fulvestrant, significantly improves progression-free survival in patients with hormone receptor-positive, HER2-negative advanced breast cancer. This suggests that Abemaciclib is effective in treating this type of breast cancer, which may support its use in combination with other drugs like Lasofoxifene. ^{1 2 3 4 5}

Is the combination of Lasofoxifene and Abemaciclib safe for breast cancer treatment?

Abemaciclib, when used with other therapies like fulvestrant, has been shown to be generally safe in treating certain types of breast cancer, with common side effects including diarrhea, infections, and low white blood cell counts. These side effects were mostly manageable. ^{1 2 3 5 6}

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

The combination of Lasofoxifene and Abemaciclib is unique because it pairs a selective estrogen receptor modulator (Lasofoxifene) with a CDK4/6 inhibitor (Abemaciclib), potentially offering a novel approach to treating hormone receptor-positive, HER2-negative breast cancer by targeting both estrogen receptors and cell cycle regulation. ^{1 2 3 5 7}

Eligibility Criteria

This trial is for pre- or postmenopausal women and men with advanced ER+/HER2- breast cancer that has worsened on certain treatments. They must have specific ESR1 mutations, be able to swallow pills, and have good organ function. Brain metastases are okay if stable and untreated by steroids. People can't join if they've had severe lung disease from treatment, need urgent chemo, progressed on similar drugs before, or have conditions increasing blood clot risks.

Inclusion Criteria

My brain metastases are stable, treated, not needing steroids, and I've had no symptoms for over 3 months.

My cancer has a specific mutation in the ESR1 gene.

I am a woman or man, regardless of my menopause status.

Exclusion Criteria

Unwilling or unable to comply with the protocol

I do not have an active infection requiring IV antibiotics or antifungals.

I am sexually active, can still have children, and won't use two forms of birth control.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either 5 mg/d of oral lasofoxifene plus oral abemaciclib 150 mg twice a day or the combination of fulvestrant 500 mg intramuscular on Days 1, 15, and 29 and then once monthly thereafter plus oral abemaciclib 150 mg twice a day

Approximately 3 years

Multiple visits as per treatment schedule

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Abemaciclib
• Fulvestrant
• Lasofoxifene

Trial Overview The study compares the effectiveness of lasofoxifene combined with abemaciclib versus fulvestrant combined with abemaciclib in treating breast cancer with an ESR1 mutation. Participants will either take lasofoxifene orally daily plus twice-daily abemaciclib or get monthly fulvestrant injections plus twice-daily abemaciclib.

Participant Groups

Group I: Treatment Experimental Treatment 1 Intervention

Pre- and Postmenopausal Women and Men with locally advanced or metastatic ER+/HER2- breast cancer who have disease progression on an AI in combination with either palbociclib or ribociclib as their first hormonal treatment for metastatic disease and who have an ESR1 mutation.

Group II: Reference Therapy Active Control 1 Intervention

Pre- and Postmenopausal Women and Men with locally advanced or metastatic ER+/HER2- breast cancer who have disease progression on an AI in combination with either palbociclib or ribociclib as their first hormonal treatment for metastatic disease and who have an ESR1 mutation.

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?

Sermonix Pharmaceuticals Inc.

Lead Sponsor

Trials

3

Recruited

630+

Findings from Research

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 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 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]

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 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]

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]

Fulvestrant is a new antiestrogen that has been shown to be effective in treating postmenopausal women with advanced breast cancer, especially after they have not responded to tamoxifen, and it has no partial agonistic effects unlike tamoxifen.

Clinical studies have demonstrated that fulvestrant has comparable efficacy to anastrozole and good tolerance among patients, leading to its approval for use in the USA and EU for those who have progressed on prior anti-estrogen therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Fulvestrant: a new agent in endocrine treatment for breast cancer]. Juretić, A., Sarić, N., Bisof, V., et al.[2018]

References

1. France pubmed.ncbi.nlm.nih.gov

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

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

Abemaciclib: First Global Approval. [2019]

3. 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]

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

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

5. United States 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. [2022]

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

MONARCH 3: Abemaciclib As Initial Therapy for Advanced Breast Cancer. [2022]

7. Croatia pubmed.ncbi.nlm.nih.gov

[Fulvestrant: a new agent in endocrine treatment for breast cancer]. [2018]