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Comparing lasofoxifene with fulvestrant for advanced breast cancer treatment

An Open Label, Randomized, Multicenter Study Comparing the Efficacy and Safety of the Combination of Lasofoxifene and Abemaciclib to the Combination of Fulvestrant and Abemaciclib for the Treatment of Pre- and Postmenopausal Women and Men With Locally Advanced or Metastatic ER+/HER2- Breast Cancer With an ESR1 Mutation

Phase 3 Interventional LeonaBio · NCT05696626

This study is testing whether a new pill called lasofoxifene works better than fulvestrant for people with advanced breast cancer that has an ESR1 mutation.

Quick facts

PhasePhase 3
Study typeInterventional
Enrollment500 (estimated)
Ages18 Years and up
SexAll
SponsorLeonaBio Industry-sponsored
Drugs / interventionschemotherapy
Locations224 sites (Scottsdale, Arizona and 223 other locations)
Trial IDNCT05696626 on ClinicalTrials.gov

What this trial studies

This clinical trial evaluates the effectiveness and safety of lasofoxifene combined with abemaciclib versus fulvestrant combined with abemaciclib in treating locally advanced or metastatic ER+/HER2- breast cancer patients who have an ESR1 mutation. Participants will receive either oral lasofoxifene or fulvestrant along with abemaciclib, with the aim of determining which combination is more effective. The study focuses on patients who have previously been treated with ribociclib or palbociclib and have shown disease progression. The trial is designed to provide insights into new treatment options for this specific patient population.

Who should consider this trial

Good fit: Ideal candidates include pre- or postmenopausal women and men with locally advanced or metastatic ER+/HER2- breast cancer who have previously received specific treatments.

Not a fit: Patients who do not have an ESR1 mutation or have not previously received ribociclib or palbociclib may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could offer a more effective treatment option for patients with advanced breast cancer and ESR1 mutations.

How similar studies have performed: Other studies have shown promise in targeting ESR1 mutations in breast cancer, suggesting that this approach may be beneficial.

Eligibility criteria

Show full inclusion / exclusion criteria 
Inclusion Criteria:

1. Pre- or postmenopausal women or men.
2. Locally advanced and/or metastatic ER+ breast cancer with radiological or clinical evidence of progression on an AI in combination with either palbociclib or ribociclib as their first hormonal treatment for metastatic disease.
3. Histological or cytological confirmation of ER+/HER2 - disease
4. No evidence of progression for at least 6 months on an AI/CDKi combination for advanced breast cancer.
5. At least 1 or more ESR1 point mutations in the ESR1 ligand binding domain as assessed in cell- free ctDNA obtained from a blood or breast cancer tissue.
6. Locally advanced or metastatic breast cancer with either measurable (according to RECIST 1.1) or non-measurable lesions.
7. Subjects may have received 1 cytotoxic chemotherapy regimen in the metastatic disease setting prior to study entry, but must have recovered from chemotherapy acute toxicity excluding alopecia and Grade 2 peripheral neuropathy.
8. Eastern Cooperative Oncology Group (ECOG) performance score of 0 or 1
9. Adequate organ function
10. Able to swallow tablets
11. Brain metastases are allowed only if the following 4 parameters hold:

    1. Asymptomatic,
    2. Definitively treated (e.g., radiotherapy, surgery),
    3. Not requiring steroids up to 4 weeks before study treatment initiation, AND
    4. Central nervous system disease stable for \>3 months prior to registration as documented by magnetic resonance imagining (MRI).
12. Able to understand and voluntarily sign a written informed consent before any screening procedures.
13. Every attempt should be made to obtain a biopsy of metastatic breast cancer tissue, when safe and feasible, to provide histological or cytological confirmation of ER+/HER2- disease as assessed by a local laboratory, according to American Society of Clinical Oncology/College of American Pathologists guidelines, using slides, paraffin blocks, or paraffin samples. If a biopsy is done, it may undergo genomic testing at some point to assess for ESR1 mutations and correlation with ctDNA results. If a biopsy is not possible or inappropriate from a clinical standpoint, the ER and HER2 status from the subject's most recent biopsy must confirm that the subject is ER+ and HER2

Exclusion Criteria:

1. Lymphangitic carcinomatosis involving the lung.
2. History of Grade 3 or Grade 4 interstitial lung disease (ILD) on previous therapy.
3. Visceral crisis in need of cytotoxic chemotherapy as assessed by the investigator.
4. Prior progression of disease on abemaciclib, fulvestrant, or other selective estrogen receptor degrader (SERD) therapy.
5. Subjects with a known hypersensitivity to fulvestrant or to any of the excipients
6. Radiotherapy within 30 days prior to Visit 0 (Day 1) except in case of localized radiotherapy for analgesic purposes or for lytic lesions at risk of fracture, which can then be completed within 7 days prior to Visit 0 (Day 1). Subjects must have recovered from radiotherapy toxicities prior to Visit 0 (Day 1).
7. Known RB1 mutations or deletions that in the opinion of the investigator confer resistance to CDK4/6i. (Screening for RB1 mutation is not required for entry.)
8. History of long QTc (Q-T interval corrected for heart rate) syndrome or a QTc of \>480 msec.
9. History of a pulmonary embolus (PE), deep vein thrombosis (DVT), or any known thrombophilia, unless the event occurred greater than 6 months prior to screening and the subject is treated with chronic anticoagulant therapy such as apixaban (Eliquis) or rivaroxaban (Xarelto).
10. Lasofoxifene is not recommended for use in subjects with conditions that place them at increased risk for VTEs (such as severe congestive heart failure \[CHF\] or prolonged immobilization).
11. On concomitant strong CYP3A4 inhibitors.
12. On strong and moderate CYP3A4 inducers.
13. Any significant co-morbidity that would impact the study or the subject's safety, including subjects with significant malabsorption.
14. Active systemic bacterial or fungal infection (requiring intravenous \[IV\] antibiotics or antifungals at the time of initiating study treatment).
15. Known infection with human immunodeficiency virus (HIV), hepatitis B virus (HBV), or hepatitis C virus (HCV).
16. History of malignancy within the past 5 years (excluding breast cancer), except basal cell or squamous cell carcinoma of the skin curatively treated by surgery.
17. Positive serum pregnancy test (only if premenopausal).
18. Sexually active premenopausal women and men unwilling to use double-barrier contraception.
19. Women who are breast feeding
20. History of non-compliance to medical regimens.
21. Unwilling or unable to comply with the protocol.
22. Current participation in any clinical research trial involving an investigational drug or device within the last 30 days.

Where this trial is running

Scottsdale, Arizona and 223 other locations

+174 more sites — see ClinicalTrials.gov for the full list.

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
View on ClinicalTrials.gov → Find more trials like this →
Conditions Metastatic Breast Cancer
Last reviewed 2026-06-13 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.