Lasofoxifene + Abemaciclib for Breast Cancer

(ELAINEII Trial)

No longer recruiting at 15 trial locations

Age: 18+

Sex: Female

Trial Phase: Phase 2

Sponsor: Sermonix Pharmaceuticals Inc.

Must be taking: Ovarian suppression

Must not be taking: CYP3A4 inhibitors, CYP3A4 inducers

Disqualifiers: Lung carcinomatosis, Visceral crisis, RB1 mutations, others

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

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: Up to 24 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new combination of two drugs, lasofoxifene and abemaciclib (a CDK4/6 inhibitor), to assess their safety and tolerability in treating certain types of breast cancer. It targets women with ER+/HER2- breast cancer, where cancer grows in response to estrogen but not due to the HER2 protein. The trial seeks women whose cancer has progressed after one or two hormonal treatments for advanced disease and who have a specific genetic mutation called ESR1. Participants should have advanced breast cancer that may have spread but remains stable after previous treatments. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

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

The trial requires that you stop taking any CDKi (a type of cancer medication) at least 21 days before starting the study. Additionally, you cannot take certain medications that strongly affect liver enzymes, like some antibiotics and antifungals. If you're on these, you might need to stop or switch them.

Is there any evidence suggesting that the combination of lasofoxifene and abemaciclib is likely to be safe for humans?

Research has shown that the combination of lasofoxifene and abemaciclib is generally well-tolerated by patients. Earlier studies demonstrated a good safety record for this combination, with patients not experiencing severe or unexpected side effects. Most people reported manageable side effects, suggesting the treatment is safe enough for further research. Additionally, the combination has shown promising results in fighting tumors in women with certain types of breast cancer, highlighting its potential benefits. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of Lasofoxifene and Abemaciclib for breast cancer because it offers a unique approach to targeting advanced ER+/HER2- breast cancer with an ESR1 mutation. Most treatments for this condition focus on hormonal therapies, but Lasofoxifene acts as a selective estrogen receptor modulator (SERM), which may help in cases where the cancer has become resistant to standard hormonal treatments. Abemaciclib, on the other hand, is a CDK4/6 inhibitor that disrupts cancer cell division. By combining these mechanisms, there's potential to more effectively combat cancer progression in patients who have exhausted other hormonal options.

What evidence suggests that the combination of lasofoxifene and abemaciclib could be effective for breast cancer?

Research shows that combining lasofoxifene and abemaciclib may help treat breast cancer with specific genetic changes. Earlier studies found this combination effective in women with ESR1-mutated, ER+/HER2- metastatic breast cancer. This treatment could potentially slow or stop cancer growth in patients with these mutations. Additionally, it has proven to be generally safe and well-tolerated by patients. These findings suggest that using lasofoxifene and abemaciclib together might offer a new treatment option for those whose cancer has worsened despite other hormonal treatments. ^{1 4 5 6 7}

Are You a Good Fit for This Trial?

This trial is for pre- and postmenopausal women with advanced or metastatic ER+/HER2- breast cancer that worsened after hormonal therapy. They must have specific ESR1 mutations, received one chemo regimen, and meet certain health criteria. Exclusions include significant other illnesses, recent serious blood clots, active infections requiring IV antibiotics, and certain drug interactions.

Inclusion Criteria

I am fully active or can carry out light work.

I am either before or after menopause.

My cancer has specific ESR1 mutations.

Exclusion Criteria

You have a history of long QT syndrome, or your QT interval is longer than 480 milliseconds.

If you are a woman who can still have children, you are pregnant.

I have hepatitis C with a measurable viral load.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive lasofoxifene and abemaciclib combination therapy for advanced or metastatic ER+/HER2- breast cancer

Up to 24 months

Visits at regular intervals as per study protocol

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Abemaciclib
• Lasofoxifene

Trial Overview The study tests a combination of lasofoxifene and abemaciclib in women whose breast cancer has progressed despite treatment. It's an open-label trial where all participants receive the drugs to assess safety and tolerability.

How Is the Trial Designed?

Group I: Treatment Experimental Treatment 1 Intervention

Women who have locally advanced or metastatic ER+/HER2- breast cancer and disease progression on first and/or 2nd lines of hormonal treatment for metastatic disease and 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+

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. sciencedirect.com sciencedirect.com/science/article/pii/S0923753423039418

Open-label, phase II, multicenter study of lasofoxifene plus ... 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/

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

4. onclive.com onclive.com/view/dr-sardesai-on-lasofoxifene-plus-abemaciclib-in-esr1-mutant-er-her2-breast-cancer

Dr Sardesai on Lasofoxifene Plus Abemaciclib in ESR1 ... The study aims to compare the progression-free survival (PFS) outcomes of 2 treatment regimens: the oral next-generation selective estrogen ...

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 ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT04432454

Study Details | NCT04432454 | Evaluation of Lasofoxifene ... This is an open-label, multicenter, single-arm safety study evaluating the safety and tolerability of the lasofoxifene and abemaciclib combination

7. 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+/ ...