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Official Title
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
Phase 3
Sponsor
Sermonix Pharmaceuticals Inc.
Enrollment
500
Timeline
Oct 2023 → Apr 2028
About This Study
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.
Eligibility Criteria
Inclusion Criteria
- 1Pre- or postmenopausal women or men.
- 2Locally 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.
- 3Histological or cytological confirmation of ER+/HER2 - disease
- 4No evidence of progression for at least 6 months on an AI/CDKi combination for advanced breast cancer.
- 5At 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.
- 6Locally advanced or metastatic breast cancer with either measurable (according to RECIST 1.1) or non-measurable lesions.
- 7Subjects 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.
- 8Eastern Cooperative Oncology Group (ECOG) performance score of 0 or 1
- 9Adequate organ function
- 10Able to swallow tablets
- 11Brain metastases are allowed only if the following 4 parameters hold:
- 12Asymptomatic,
- 13Definitively treated (e.g., radiotherapy, surgery),
- 14Not requiring steroids up to 4 weeks before study treatment initiation, AND
- 15Central nervous system disease stable for \>3 months prior to registration as documented by magnetic resonance imagining (MRI).
- 16Able to understand and voluntarily sign a written informed consent before any screening procedures.
- 17Every 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
- 1Lymphangitic carcinomatosis involving the lung.
- 2History of Grade 3 or Grade 4 interstitial lung disease (ILD) on previous therapy.
- 3Visceral crisis in need of cytotoxic chemotherapy as assessed by the investigator.
- 4Prior progression of disease on abemaciclib, fulvestrant, or other selective estrogen receptor degrader (SERD) therapy.
- 5Subjects with a known hypersensitivity to fulvestrant or to any of the excipients
- 6Radiotherapy 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).
- 7Known 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.)
- 8History of long QTc (Q-T interval corrected for heart rate) syndrome or a QTc of \>480 msec.
- 9History 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).
- 10Lasofoxifene 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).
- 11On concomitant strong CYP3A4 inhibitors.
- 12On strong and moderate CYP3A4 inducers.
- 13Any significant co-morbidity that would impact the study or the subject's safety, including subjects with significant malabsorption.
- 14Active systemic bacterial or fungal infection (requiring intravenous \[IV\] antibiotics or antifungals at the time of initiating study treatment).
- 15Known infection with human immunodeficiency virus (HIV), hepatitis B virus (HBV), or hepatitis C virus (HCV).
- 16History of malignancy within the past 5 years (excluding breast cancer), except basal cell or squamous cell carcinoma of the skin curatively treated by surgery.
- 17Positive serum pregnancy test (only if premenopausal).
- 18Sexually active premenopausal women and men unwilling to use double-barrier contraception.
- 19Women who are breast feeding
- 20History of non-compliance to medical regimens.
- 21Unwilling or unable to comply with the protocol.
- 22Current participation in any clinical research trial involving an investigational drug or device within the last 30 days.
Locations
222 sites participating in this study
Emory University School of Medicine
Atlanta, Georgia 30322
Jane Meisel
Mayo Clinic - Scottsdale
Scottsdale, Arizona 85259
Clinical Trials Office - All Mayo Clinic Locations
University of Arizona - Cancer Center
Tucson, Arizona 85719
Carissa Ganzer
Data sourced from ClinicalTrials.govView on ClinicalTrials.gov →