Inclusion Criteria:

          1. Signed informed consent form (ICF) prior to participation in any study-related
             activities.

          2. Male or female patients ≥18 years at the time of signing the ICF.

          3. Eastern Cooperative Oncology Group performance status of 0 or 1.

          4. Life expectancy of at least 24 weeks.

          5. Pre menopausal or peri menopausal women who are being treated with a luteinizing
             hormone-releasing hormone analog for at least 28 days prior to study entry (if
             shorter, post-menopausal levels of serum estradiol/follicle-stimulating hormone [FSH]
             must be confirmed analytically) or post menopausal women as defined by any of the
             following criteria:

               1. Documented bilateral oophorectomy;

               2. Age ≥60 years;

               3. Age <60 years and cessation of regular menses for ≥12 consecutive months with no
                  alternative pathological or physiological cause; and serum estradiol and/or FSH
                  level within the laboratory's reference range for post-menopausal females.

          6. Unresectable locally advanced or MBC that is not amenable to resection with curative
             intent.

          7. At least one of the following aggressive disease criteria:

               1. Presence of visceral disease;

               2. Either radiological as per RECIST v1.1 or clinical evidence of progressive
                  disease (PD) on or within 36 months of completing adjuvant ET;

               3. High histological grade and/or PgR-negative status on primary tumor;

               4. Lactate dehydrogenase (LDH) >1.5 × the upper limit of normal (ULN).

          8. Histologically confirmed estrogen receptor and/or progesterone receptor (PgR) positive
             (with ≥1% positive stained cells according to National Comprehensive Cancer Network
             and American Society of Clinical Oncology guidelines) and HER2 negative (0 to 1+ by
             immunohistochemistry or 2+ and negative by in situ hybridization test) breast cancer
             based on local testing on the most recent analyzed biopsy.

          9. Measurable disease as per RECIST v 1.1 with at least one site of disease amenable to
             biopsy. Patients with bone lesions as the only sites of metastatic disease are not
             eligible, except for patients with identifiable soft tissue components, evaluable by
             cross sectional imaging techniques such as CT or magnetic resonance imaging (MRI), and
             that meet the definition of measurability according to RECIST v1.1.

             Note: Previously irradiated lesions can only be considered as measurable disease if
             disease progression has been unequivocally documented at that site since radiation.

         10. Willingness and ability to provide a tumor biopsy from a metastatic site or the
             primary breast tumor at the time of the inclusion to perform exploratory studies. If
             not feasible, patient eligibility should be evaluated by Sponsor's qualified designee.

         11. Willingness to provide blood samples for exploratory studies at baseline, after two
             weeks of study treatment and at progression (or study treatment termination prior to
             start alternative anti cancer therapy).

         12. Patients relapsing on a cyclin-dependent kinase (CDK) 4/6 inhibitor based regimen in
             the neoadjuvant or adjuvant setting will be suitable for the study if disease
             progression is confirmed after at least 12 months following CDK 4/6 treatment
             completion.

         13. No prior systemic therapy for unresectable locally advanced or metastatic disease.

         14. Radiation therapy for metastatic disease is permitted but the patient must have fully
             recovered from the acute effects and at least 14 days must have elapsed between the
             last dose and randomization.

             Note: For limited-field radiotherapy, at least 7 days must have elapsed between the
             last dose and randomization.

         15. Resolution of all acute toxic effects of prior anti cancer therapy to Grade ≤1 as
             determined by the NCI-CTCAE v 5.0 (except for Grade ≤2 neuropathy, alopecia, or other
             toxicities not considered a safety risk for the patient at investigator's discretion)
             within at least 14 days prior to study Day 1.

         16. Adequate hematologic and organ function within 14 days before the first study
             treatment on Day 1 of Cycle 1, defined by the following:

               1. Hematological: White blood cell count >3.0 × 109/L; Absolute neutrophil count
                  ≥1.5 × 109/L (without granulocyte colony-stimulating factor support within 2
                  weeks prior to Cycle 1, Day 1); Platelet count ≥100 × 109/L (without transfusion
                  within 2 weeks prior to Cycle 1, Day 1); Hemoglobin >9.0 g/dL (without
                  transfusion within 2 weeks prior to Cycle 1, Day 1).

               2. Hepatic:

             i. Serum albumin ≥ 3 g/dL; ii. Total bilirubin ≤ 1.5 × ULN (≤2 × ULN in the case of
             Gilbert's disease); iii. Aspartate transaminase and alanine transaminase ≤3.0 × ULN
             (in the case of liver metastases ≤5 × ULN); iv. Alkaline phosphatase ≤2.5 × ULN (in
             the case of liver and/or bone metastases ≤ 5 × ULN).

             c. Renal: i. Serum creatinine <1.5 × ULN or creatinine clearance ≥30 mL/min based on
             Cockcroft-Gault glomerular filtration rate estimation.

             d. Coagulation: i. Partial thromboplastin time (or activated partial thromboplastin
             time and international normalized ratio ≤1.5×ULN.

         17. For women of childbearing potential: agreement to remain abstinent (refrain from
             heterosexual intercourse) or use highly effective contraceptive methods, or two
             effective contraceptive methods, as defined in the protocol during the treatment
             period and for at least 3 weeks after the last dose of study treatment, and agreement
             to refrain from donating eggs during this same period. Women of childbearing potential
             must have a negative serum pregnancy test within 7 days before study treatment
             initiation.

         18. Male patients should also have their partners who are women of childbearing potential
             use highly effective contraceptive methods, or two effective contraceptive methods, as
             defined in the protocol during the treatment period and for at least 3 weeks after the
             last dose of study treatment and refrain from donating sperm during this period.

         19. Able to swallow oral medication.

         20. Patients who are reliable, willing to be available for the duration of the study and
             are willing to follow study procedures.

        Exclusion Criteria:

          1. Known hypersensitivity to abemaciclib, letrozole, fulvestrant, paclitaxel, and/or any
             of their excipients.

          2. Are currently receiving an investigational drug in a clinical study or participating
             in any other type of medical research judged not to be scientifically or medically
             compatible with this study.

             Note: For patients who stopped receiving an investigational drug in another clinical
             study, a washout period of 21 days or 5-half-lives (whichever is shorter) must be
             observed before entering the trial.

          3. Formal contraindication to ET defined as visceral crisis and rapidly or symptomatic
             progressive visceral disease.

          4. Known concurrent malignancy or malignancy within 5 years of study enrollment except
             for carcinoma in situ of the cervix, non melanoma skin carcinoma, or stage I uterine
             cancer. For other cancers considered to have a low risk of recurrence, discussion with
             the medical monitor is required.

          5. Known active brain metastases and/or carcinomatous meningitis. Participants with
             previously treated brain metastases may participate provided they are radiologically
             stable for ≥4 weeks by repeat imaging (note that the repeat imaging should be
             performed during study screening), clinically stable, and without requirement of
             steroid treatment for ≥14 days prior to first dose of study treatment.

          6. Known psychiatric or substance abuse disorders that would interfere with cooperation
             with the requirements of the study.

          7. Major surgical procedure within 14 days prior to treatment initiation or anticipation
             of the need for a major surgical procedure during the course of the study other than
             for diagnosis.

             Note: Placement of central venous access catheter(s) (e.g., port or similar) is not
             considered a major surgical procedure and is therefore permitted.

          8. Active bleeding diathesis, previous history of bleeding diathesis, or chronic
             anti-coagulation treatment (the use of low molecular weight heparin is allowed if used
             prophylactically).

          9. Serious and/or uncontrolled pre existing medical condition(s) that, in the judgment of
             the investigator, would preclude participation in this study (for example,
             interstitial lung disease, severe dyspnea at rest or requiring oxygen therapy, severe
             renal impairment [e.g., estimated creatinine clearance <30 ml/min], history of major
             surgical resection involving the stomach or small bowel, or pre-existing Crohn's
             disease or ulcerative colitis or a pre existing chronic condition resulting in
             baseline Grade 2 or higher diarrhea).

         10. Current known infection with HIV, hepatitis B virus (HBV), or hepatitis C virus (HCV).
             Patients with past HBV infection or resolved HBV infection (defined as having a
             negative hepatitis B surface antibody [HBsAg] test and a positive hepatitis B core
             antibody [HBcAb] test, accompanied by a negative HBV DNA test) are eligible. Patients
             positive for HCV antibody are eligible only if polymerase chain reaction (PCR) is
             negative for HCV RNA.

         11. Active bacterial or fungal infection at the time of enrolment (requiring antibiotics
             or antifungal agents at time of initiating study treatment).

         12. History of any of the following conditions: syncope of cardiovascular etiology,
             ventricular arrhythmia of pathological origin (including, but not limited to,
             ventricular tachycardia and ventricular fibrillation), or sudden cardiac arrest.

         13. Pregnant, breastfeeding, or expecting to conceive or father children within the
             projected duration of the study, starting with the screening visit through at least 3
             weeks after the last dose of study treatment.