• 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.

⁃ 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