Lasofoxifene and Abemaciclib vs Fulvestrant and Abemaciclib for Breast Cancer

(ELAINEIII Trial)

Recruiting at 264 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests two medication combinations to determine which is more effective for a specific type of breast cancer. It targets advanced breast cancer that is estrogen receptor positive (ER+) and human epidermal growth factor 2 negative (HER2-), with a mutation known as ESR1. Participants will receive either lasofoxifene (a selective estrogen receptor modulator) and abemaciclib (a CDK4/6 inhibitor) or fulvestrant (an estrogen receptor antagonist) and abemaciclib to compare effectiveness and safety. Those with advanced ER+/HER2- breast cancer, whose disease has progressed after treatments like ribociclib or palbociclib, might be suitable for this trial. 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.

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.

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

Research shows that the combination of lasofoxifene and abemaciclib is generally easy for most people to handle. Earlier studies found this combination had an acceptable safety profile, with most participants not experiencing serious side effects. It was well-tolerated and effective in reducing tumors in patients with certain types of breast cancer, including those with ESR1 mutations.

Similarly, the combination of fulvestrant and abemaciclib has been used before and is known to be safe. This combination is approved for treating some advanced breast cancers, indicating it is generally safe for patients.

For those considering joining the trial, both treatment options have shown acceptable safety levels in the past. However, individual experiences may vary, so discussing possible side effects with a healthcare provider is advisable. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments because Lasofoxifene and Abemaciclib represent a potentially groundbreaking combination for treating ER+/HER2- breast cancer. Unlike the standard options like Fulvestrant combined with Abemaciclib, Lasofoxifene is a selective estrogen receptor modulator (SERM) that might offer a new way to target cancer cells with an ESR1 mutation. This dual approach could improve outcomes by acting on estrogen receptors differently, possibly reducing resistance that often develops with current treatments. Moreover, combining Lasofoxifene with Abemaciclib, a CDK4/6 inhibitor, could enhance the effectiveness against cancer progression, offering hope for patients who have seen limited success with other therapies.

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

In this trial, participants will receive either the combination of lasofoxifene and abemaciclib or the combination of fulvestrant and abemaciclib. Research has shown that combining lasofoxifene and abemaciclib may effectively treat breast cancer with an ESR1 mutation, as studies have found that this combination can help shrink tumors or slow their growth. Lasofoxifene has performed well against ESR1 mutations, whether used alone or with drugs like abemaciclib, suggesting it might benefit patients whose cancer has worsened after previous treatments. Meanwhile, fulvestrant with abemaciclib is a known treatment that has benefited many patients with similar breast cancer. This trial will compare both treatment options to determine which is more effective for people with advanced breast cancer. ^{1 2 3 4 6}

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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 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]

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]

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]

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]

Citations

1. onclive.com onclive.com/view/lasofoxifene-aims-to-amplify-efficacy-of-abemaciclib-in-esr1-mutated-er-her2-metastatic-breast-cancer

Lasofoxifene Aims to Amplify Efficacy of Abemaciclib in ... Lasofoxifene plus abemaciclib is set to be evaluated in ESR1-mutated ER+/HER2– metastatic breast cancer in the phase 3 ELAINEIII trial.

2. annalsofoncology.org annalsofoncology.org/article/S0923-7534(23)03941-8/fulltext

breast cancer and an ESR1 mutation after disease ... Lasofoxifene plus abemaciclib had an acceptable safety profile, was well tolerated, and exhibited meaningful antitumor activity in women with ESR1-mutated, ER+/ ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12051526/

ELAINE 3: phase 3 study of lasofoxifene plus abemaciclib to ... The phase 3, randomized ELAINE 3 trial will evaluate the efficacy and safety of lasofoxifene/abemaciclib versus fulvestrant/abemaciclib for ...

4. cancernetwork.com cancernetwork.com/view/lasofoxifene-plus-abemaciclib-induces-response-in-previously-treated-er-her2-esr1-metastatic-breast-cancer

Lasofoxifene Plus Abemaciclib Induces Response in ... Lasofoxifene has shown activity against ESR1 mutations alone or in combination with CDK4/6 inhibition vs fulvestrant in preclinical studies.

5. clinicaltrials.gov clinicaltrials.gov/study/NCT05696626

NCT05696626 | Evaluation of Lasofoxifene Combined With ... The goal of this clinical trial is to assess the efficacy, safety and tolerability of the combination of lasofoxifene and abemaciclib compared to fulvestrant ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT05696626

NCT05696626 | Evaluation of Lasofoxifene Combined With ... The goal of this clinical trial is to assess the efficacy, safety and tolerability of the combination of lasofoxifene and abemaciclib compared to ...