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

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 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. 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.