Evaluation of Lasofoxifene Combined With Abemaciclib Compared With Fulvestrant Combined With Abemaciclib in Locally Advanced or Metastatic ER+/HER2- Breast Cancer With an ESR1 Mutation

Launched by SERMONIX PHARMACEUTICALS INC. · Jan 13, 2023

Keywords

ClinConnect Summary

This clinical trial is studying a new treatment for people with advanced breast cancer that is estrogen receptor positive (ER+) and has specific changes in a gene called ESR1. The trial is comparing two treatment combinations: one that includes a medication called lasofoxifene with another called abemaciclib, and the other that combines fulvestrant with abemaciclib. The aim is to see which combination works better in treating patients who have already been on other hormone therapies.

To be eligible for this trial, participants need to be pre- or postmenopausal women or men with advanced breast cancer that has progressed after treatment with certain other drugs. They should have a confirmed ESR1 mutation and be able to take medications by mouth. Participants will take either lasofoxifene or fulvestrant along with abemaciclib for a set period. Throughout the trial, doctors will closely monitor the participants for any side effects and to see how well the treatments are working. If you're considering joining this study, you'll need to discuss it with your doctor to understand if it's the right option for you.

Gender

ALL

Eligibility 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.
• 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.