Brief Summary
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 advancedat a late stage, far along 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.
Intervention / Treatment
- Drug: Lasofoxifene in combination with abemaciclib
- Drug: Fulvestrant in combination with abemaciclib
Inclusion Criteria:
- Pre- or postmenopausal women or men.
- 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.
- Histological or cytological confirmation of ER+/HER2 – disease
- No evidence of progression for at least 6 months on an AI/CDKi combination for advanced breast cancer.
- 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.
- Locally advanced or metastatic breast cancer with either measurable (according to RECIST 1.1) or non-measurable lesions.
- Subjects may have received 1 cytotoxic chemotherapya cancer treatment that uses drugs to kill or slow the growth of cancer cells, while minimising damage to healthy cells regimen in the metastatic disease setting prior to study entry, but must have recovered from chemotherapy acute toxicity excluding alopeciathe partial or complete absence of hair from areas of the body where it normally grows; baldness and Grade 2 peripheral neuropathy.
- Eastern Cooperative Oncology Group (ECOG) performance score of 0 or 1
- Adequate organ function
- Able to swallow tablets
- Brain metastases are allowed only if the following 4 parameters hold:
- Asymptomatic,
- Definitively treated (e.g., radiotherapy, surgery),
- Not requiring steroids up to 4 weeks before study treatment initiation, AND
- Central nervous system disease stable for >3 months prior to registration as documented by magnetic resonance imagining (MRI).
- Able to understand and voluntarily sign a written informed consent before any screening procedures.