Lasofoxifene and Abemaciclib vs Fulvestrant and Abemaciclib for Breast Cancer (ELAINEIII Trial)
Recruiting in Palo Alto (17 mi)
+192 other locations
Age: 18+
Sex: Any
Travel: May be covered
Time Reimbursement: Varies
Trial Phase: Phase 3
Recruiting
Sponsor: Sermonix Pharmaceuticals Inc.
No Placebo Group
Pivotal Trial (Near Approval)
Prior Safety Data
Breakthrough Therapy
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.
12345Is 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.
12356What 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.
12357Eligibility 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 cancer has a specific mutation in the ESR1 gene.
I am a woman or man, regardless of my menopause status.
I am fully active or have some restrictions but can still care for myself.
My breast cancer has spread and can be measured or seen on scans.
I can swallow pills.
My cancer is ER positive and HER2 negative.
My ER+ breast cancer has worsened on my first hormone therapy for its advanced stage.
My advanced breast cancer hasn't worsened in 6 months while on AI/CDKi treatment.
Exclusion Criteria
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.
I am taking medication that strongly affects liver enzymes.
My cancer progressed despite treatment with specific hormone therapies.
I have had severe lung issues due to past treatments.
My cancer has spread to the lymph vessels in my lungs.
I need strong chemotherapy for a severe crisis in my organs.
I do not have any major health issues that could affect my safety in the study.
I do not have conditions like severe heart failure or long-term immobility that increase my risk for blood clots.
I have had a blood clot in my lungs or veins, or I have a condition that increases my risk of blood clots.
I am currently taking strong CYP3A4 inhibitor medications.
I have been diagnosed with HIV, HBV, or HCV.
Participant Groups
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.
2Treatment groups
Experimental Treatment
Active Control
Group I: TreatmentExperimental Treatment1 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 TherapyActive Control1 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
Find A Clinic Near You
Research locations nearbySelect from list below to view details:
New Jersey Cancer Care, PABelleville, NJ
Allina Health System DBA Virginia Piper Cancer InstituteMinneapolis, MN
Henry Ford Health SystemDetroit, MI
MD Anderson Cancer CenterHouston, TX
More Trial Locations
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Who is running the clinical trial?
Sermonix Pharmaceuticals Inc.Lead Sponsor
References
Abemaciclib: A Review in Early Breast Cancer with a High Risk of Recurrence. [2023]Abemaciclib [Verzenio® (USA) or Verzenios® (EU)] is a cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitor approved in combination with adjuvant endocrine therapy for patients with hormone receptor positive (HR+), human epidermal growth factor receptor 2 negative (HER2-), node-positive, early breast cancer with a high risk of recurrence. In a phase III trial, abemaciclib plus endocrine therapy reduced the risk of recurrence of breast cancer compared with endocrine therapy alone, including in patients who had previously received neoadjuvant chemotherapy, in patients with high- and low-scoring Ki-67 tumours, and in both premenopausal and postmenopausal patients. The tolerability profile of abemaciclib plus endocrine therapy was acceptable and manageable, with diarrhoea, infections and neutropenia being the most common adverse events. Thus, abemaciclib in combination with standard endocrine therapy is a valuable additional treatment option for patients with HR+, HER2-, node-positive early breast cancer with a high risk of recurrence.
Abemaciclib: First Global Approval. [2019]Abemaciclib (Verzenio™) is an orally administered inhibitor of cyclin-dependent kinases 4 and 6 that is being developed by Eli Lilly and Company. Abemaciclib has been approved in the USA for the treatment of hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced or metastatic breast cancer, in combination with fulvestrant in women with disease progression following endocrine therapy, and as monotherapy in adult patients with disease progression following endocrine therapy and prior chemotherapy in the metastatic setting. In addition, abemaciclib is in various stages of development internationally for a variety of cancers. This article summarizes the milestones in the development of abemaciclib leading to its first approval for the treatment of patients with HR-positive, HER2-negative advanced or metastatic breast cancer.
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]Abemaciclib in combination with endocrine therapy (ET) has demonstrated significant efficacy benefits in HR+ , HER2- advanced breast cancer patients in the Phase 3 studies MONARCH 2 (fulvestrant as ET) and MONARCH 3 (letrozole or anastrozole as ET). Here, we report age-specific safety and efficacy outcomes.
First-Line Abemaciclib Effective in ER+ Breast Cancer. [2019]Interim data from the MONARCH3 study indicate that abemaciclib is an effective first-line therapy for advanced ER-positive, HER2-negative breast cancer. Adding the investigational CDK4/6 inhibitor to letrozole significantly improved patients' progression-free survival, compared with those given a placebo alongside endocrine therapy.
MONARCH 2: Subgroup Analysis of Patients Receiving Abemaciclib Plus Fulvestrant as First-Line and Second-Line Therapy for HR+, HER2--Advanced Breast Cancer. [2022]Label="PURPOSE">In MONARCH 2, abemaciclib plus fulvestrant significantly prolonged progression-free survival (PFS) and overall survival (OS) versus placebo plus fulvestrant in patients with hormone receptor positive (HR+), HER2- advanced breast cancer. This exploratory analysis assessed the efficacy of abemaciclib plus fulvestrant across subgroups of patients receiving study therapy as first- or second-line treatment for metastatic disease.
MONARCH 3: Abemaciclib As Initial Therapy for Advanced Breast Cancer. [2022]Purpose Abemaciclib, a cyclin-dependent kinase 4 and 6 inhibitor, demonstrated efficacy as monotherapy and in combination with fulvestrant in women with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer previously treated with endocrine therapy. Methods MONARCH 3 is a double-blind, randomized phase III study of abemaciclib or placebo plus a nonsteroidal aromatase inhibitor in 493 postmenopausal women with HR-positive, HER2-negative advanced breast cancer who had no prior systemic therapy in the advanced setting. Patients received abemaciclib or placebo (150 mg twice daily continuous schedule) plus either 1 mg anastrozole or 2.5 mg letrozole, daily. The primary objective was investigator-assessed progression-free survival. Secondary objectives included response evaluation and safety. A planned interim analysis occurred after 189 events. Results Median progression-free survival was significantly prolonged in the abemaciclib arm (hazard ratio, 0.54; 95% CI, 0.41 to 0.72; P = .000021; median: not reached in the abemaciclib arm, 14.7 months in the placebo arm). In patients with measurable disease, the objective response rate was 59% in the abemaciclib arm and 44% in the placebo arm ( P = .004). In the abemaciclib arm, diarrhea was the most frequent adverse effect (81.3%) but was mainly grade 1 (44.6%). Comparing abemaciclib and placebo, the most frequent grade 3 or 4 adverse events were neutropenia (21.1% v 1.2%), diarrhea (9.5% v 1.2%), and leukopenia (7.6% v 0.6%). Conclusion Abemaciclib plus a nonsteroidal aromatase inhibitor was effective as initial therapy, significantly improving progression-free survival and objective response rate and demonstrating a tolerable safety profile in women with HR-positive, HER2-negative advanced breast cancer.
[Fulvestrant: a new agent in endocrine treatment for breast cancer]. [2018]Tamoxifen is considered to be the gold standard in hormonotherapy of patients with estrogen dependent breast cancer (estrogen receptor (ER) and/or progesterone receptor (PR) positive tumors). However, because tamoxifen's beneficial effects diminish after 5 years of use in adjuvant setting and because of its partial agonistic effects and its resistence to tamoxifen in some breast carcinoma, there is a need for new antiestrogens. One of these antiestrogens is fulvestrant which, unlike tamoxifen, has no partial agonistic effects. Its efficacy has been confirmed in preclinical and in recent phase III clinical studies in postmenopausal patients. In disease recurrence after adjuvant tamoxifen or progressive disease on-first-line tamoxifen treatment fulvestrant is comparable with (similar to) anastrozole. When compared with tamoxifen as first-line treatment in patients with advanced cancer, only in patients with ER and/or PR positive tumors similar results have also been obtained. In both trials tolerance to fulvestrant has been good. Following the results of these clinical studies fulvestrant has already been licenced in the USA and EU for the treatment of postmenopausal women with advanced breast cancer who had progressed on prior anti-estrogen therapy.