Inclusion Criteria:

          1. Pre- or postmenopausal.

             Postmenopausal women are defined as:

               1. ≥ 60 years of age with no vaginal bleeding over the prior year, or

               2. < 60 years with "premature menopause" or "premature ovarian failure" manifest
                  itself with secondary amenorrhea for at least 1 year and follicle stimulating
                  hormone (FSH) and estradiol levels in the postmenopausal range according to
                  institutional standards, or

               3. surgical menopause with bilateral oophorectomy. Note: Premenopausal women who
                  meet all of the other entry criteria must be maintained on ovarian suppression
                  (such as Lupron) during the study and subjects counseled to use appropriate
                  contraception to prevent pregnancy.

          2. If possible, a biopsy of metastatic breast cancer tissue should be obtained 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 not possible, the ER and HER2 status from the tissue obtained at the time of
             the original diagnosis must confirm that the subject is ER+ and HER2-.

          3. Locally advanced and/or metastatic breast cancer with radiological or clinical
             evidence of progression on the first or 2nd lines of hormonal therapy for metastatic
             disease. Progression may have occurred on no more than 2 of the following endocrine
             treatments for metastatic breast cancer: an aromatase inhibitor (AI) and/or
             fulvestrant either as monotherapy or in combination with any commercially approved
             CDKi; and/or the combination of fulvestrant and everolimus; and/or the combination of
             fulvestrant and alpelisib; and/or tamoxifen; and/or the combination of
             exemestane/everolimus. (Note: before starting study treatment, subjects should have
             stopped any CDKi for at least 21 days)

          4. Subjects must have had no evidence of progression for at least 6 months during their
             first hormonal treatment for advanced breast cancer.

          5. At least one or more of the following ESR1 point mutations as assessed in cell-free
             circulating tumor DNA (ctDNA) obtained from a blood or tissue sample: Y537S, Y537C,
             D538G, E380Q, S463P, V534E, P535H, L536H, L536P, L536R, L536Q, or Y537N. Note: the
             Sponsor's blood ctDNA assay must be used but tissue sequencing (if done) may be done
             by a validated commercial laboratory.

             Note: A positive ESR1 mutation in tissue or ctDNA using a validated commercial assay
             if done prior or at the time of disease progression is acceptable to meet this entry
             criteria. However, blood for ctDNA must still be obtained for genomic analyses using
             the sponsor's ctDNA assay.

          6. Locally advanced or metastatic breast cancer with either measurable (according to
             RECIST 1.1) or non-measurable lesions.

          7. Subjects may have received one cytotoxic chemotherapy regimen for metastatic disease
             as well as those who received one cytotoxic chemotherapy regimen in the neo-adjuvant
             or adjuvant setting prior to entry into the trial can be enrolled but must be free of
             all chemotherapy acute toxicity excluding alopecia and Grade 2 peripheral neuropathy
             before study entry. A washout period of at least 21 days is required between last
             chemotherapy dose and entry into the study.

          8. Stable breast cancer metastasis to the brain is allowed as long as the subject has
             received radiotherapy and not demonstrated any evidence of brain metastasis
             progression for at least 3 months after the completion of radiotherapy.

          9. ECOG performance score of 0 or 1.

         10. Adequate organ function as shown by:

               1. absolute neutrophil count (ANC) ≥ 1,500 cells/mm3

               2. platelet count ≥ 100,000 cells/mm3

               3. hemoglobin ≥ 8.0 g/dl

               4. ALT and AST levels ≤ 3 upper limit of normal (ULN) or ≤ 5 in the presence of
                  liver metastasis

               5. total serum bilirubin ≤ 1.5 X ULN (≤ 3 X ULN for subjects known to have Gilbert
                  Syndrome)

               6. alkaline phosphatase level ≤ 3 ULN

               7. creatinine clearance of 40 ml/min or greater as calculated by the Cockcroft-Gault
                  formula

               8. International normalized ratio (INR) and activated partial thromboplastin (aPTT)
                  < 2.0 X ULN

         11. Able to swallow tablets.

         12. Able to understand and voluntarily sign a written informed consent before any
             screening procedures.

        Exclusion Criteria:

          1. Lymphangitic carcinomatosis involving the lung.

          2. Visceral crisis in need of cytotoxic chemotherapy as assessed by the investigator.

          3. Radiotherapy within 30 days prior to entry into the study 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 entry into the study. Subjects must have
             recovered from radiotherapy toxicities prior to entry into the study.

          4. Subjects with known inactivating RB1 mutations or deletions (Screening for RB1
             mutation is not required for entry).

          5. History of long QTC syndrome or a QTC of > 480 msec.

          6. History of a pulmonary embolus (PE) or deep vein thrombosis (DVT) within the last 6
             months or any known thrombophilia. Subjects stable on anti-coagulants for maintenance
             are eligible as long as the DVT and/or PE occurred > 6 months prior to enrollment and
             there is no evidence for active thrombosis. The use of low-dose ASA is permitted.

          7. Subjects on concomitant strong CYP3A4 inhibitors such as clarithromycin,
             telithromycin, nefazodone, itraconazole, ketoconazole, atazanavir, darunavir,
             indinavir, lopinavir, nelfinavir, ritonavir, saquinavir, tipranavir.

          8. Subjects on strong and moderate CYP3A4 inducers such as amprenavir, barbiturates,
             carbamazepine, clotrimazole, dexamethasone, efavirenz, ethosuximide, griseofulvin,
             modafinil, nevirapine, oxcarbazepine, phenobarbital, phenytoin, chronic prednisone
             treatment, primidone, rifabutin, rifampin, rifapentine, ritonavir, topiramate.

          9. Any significant co-morbidity that would impact the study or the subject's safety.
             Since CDKi have reported the occurrence of interstitial lung disease (ILD), subjects
             with a history of ILD and those with severe dyspnea at rest or requiring oxygen
             therapy should not enter the study

         10. Subject has an active systemic bacterial or fungal infection (requiring intravenous
             [IV] antibiotics at the time of initiating study treatment).

         11. History of a positive human immunodeficiency virus (HIV) or hepatitis B virus (HBV)
             test. Screening is not required for enrollment.

         12. Subjects with hepatitis C virus (HCV) at Screening who still have a viral load.
             Subjects previously treated and achieved a HCV cure (no viral load) can be entered
             into the study

         13. 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, or
             early-stage cervical cancer.

         14. Positive serum pregnancy test (only if premenopausal).

         15. History of non-compliance to medical regimens.

         16. Unwilling or unable to comply with the protocol.

         17. Current participation in any clinical research trial involving an investigational drug
             or device within the last 30 days.