VS-6766+Abema+Fulv in Met HR+/HER- BC

Inclusion Criteria: * Participants must have histologically or cytologically confirmed hormone receptor positive (HR+), HER2 negative metastatic or locally recurrent unresectable invasive breast cancer. ER, PR and HER2 measurements should be performed according to institutional guidelines, in a CLIA-approved setting. Cut-off values for positive/negative staining should be in accordance with current ASCO/CAP (American Society of Clinical Oncology/College of American Pathologists) guidelines. * Participants may have measurable or non-measurable disease according to RECIST v1.1. * Men and pre- and postmenopausal women are eligible. Ongoing monthly GNRH agonist is required in pre-menopausal women or male participants for at least 4 weeks prior to study entry. If men or pre-menopausal women have not received regular GNRH agonist for at least 4 weeks prior to study entry, these patients will be excluded. * Participants must have radiological or objective evidence of progression on any CDK 4/6 inhibitor-containing regimen in the metastatic setting, and/or relapse/progression during or within 12 months of completion of any CDK4/6 inhibitor-containing regimen in the adjuvant setting. * It is not mandatory to have a CDK4/6 inhibitor-containing regimen as the most recent treatment. * Participants must have radiological or objective evidence of progression on fulvestrant (as a single agent or as a component of any multi-drug regimen) in the metastatic setting. * It is not mandatory to have a fulvestrant-containing regimen as the most recent treatment. * Prior therapy: * No more than two prior chemotherapy regimens in the metastatic setting. * For both the phase I and phase II portions of this trial, there is no limit on prior lines of endocrine therapy in the adjuvant or metastatic setting. * For phase 2 cohort only: Willing to undergo pre- and on-treatment tumor biopsies. Patients are exempt from this requirement if, in the opinion of the investigator, the biopsy procedure would pose a significant risk. Biopsies are optional in the phase 1 cohort. * ECOG performance status \<2. * Participants must have normal organ and marrow function as defined below: * absolute neutrophil count ≥ 1.5 x 109/L * platelets ≥100,000/μl * hemoglobin ≥9 g/dL (If red blood cell transfusion has been administered, hemoglobin must remain stable and ≥9 g/dL without further transfusion for at least 1 week prior to first dose of study therapy). * total bilirubin ≤1.5mg/dL (≤3.0mg/dL in patients with known Gilbert syndrome and direct bilirubin within normal limits) * AST(SGOT)/ALT(SGPT) ≤2.5 × institutional ULN. * Adequate renal function with a creatinine clearance rate of ≥ 50 mL/min as calculated by the Cockcroft-Gault formula. * International normalized ratio (INR) ≤ 1.5 and partial thromboplastin time (PTT) ≤ 1.5 x ULN in the absence of anticoagulation or therapeutic levels in the presence of anticoagulation. * Creatine phosphokinase (CPK) ≤ 2.5 x ULN. * Adequate cardiac function with left ventricular ejection fraction ≥ 50% by echocardiography (ECHO) or multiple-gated acquisition (MUGA) scan. * Baseline QTc interval \< 480 ms (average of triplicate readings) using Fredericia's QT correction formula. NOTE: This criterion does not apply to patients with a complete or incomplete right or left bundle branch block. * Adequate recovery from toxicities related to prior systemic treatments, surgery, or radiotherapy to at least Grade 1 by CTCAE v 5.0. Exceptions include alopecia and peripheral neuropathy grade ≤ 2. * Age \>18 years. Because no dosing or adverse event data are currently available on the use of study agents in participants \<18 years of age, children are excluded from this study. * Women of childbearing potential, women who are made postmenopausal through use of GNRH agonists, and men must agree to use adequate contraception for the duration of protocol treatment. Women meeting these criteria will need to use adequate contraception for at least 30 days after the last dose of abemaciclib or VS-6766 and for one year after the last dose of fulvestrant. Men will need to use adequate contraception for 90 days after the last dose of abemaciclib or VS-6766 and for one year after the last dose of fulvestrant. Additionally, males must agree not to donate sperm for the duration of protocol treatment and for at least 90 days after the last dose of protocol therapy. Childbearing potential for this purpose is defined as: those who have not been surgically sterilized and/or have had a menstrual period in the past 12 months. Adequate contraception is defined as one highly effective non-hormonal form of contraception or two effective forms of non-hormonal contraception by the participant and/or partner: Highly Effective Non-Hormonal Contraception Methods of birth control which result in a low failure rate (i.e., less than 1% per year) when used consistently and correctly are considered highly-effective forms of contraception. The following non-hormonal methods of contraception are acceptable: * True abstinence when this is in line with the preferred and usual lifestyle of the participant. \[Periodic abstinence (e.g., calendar, ovulation, symptothermal post-ovulation methods) and withdrawal are not acceptable methods of contraception\]. * Male sterilization (with appropriate post-vasectomy documentation of the absence of sperm in the ejaculate). For female participants, the vasectomized male partner should be the sole partner. OR Effective Non-Hormonal Contraception Alternatively two of the following effective forms of contraception may be used instead: * Placement of non-hormonal or progesterone-coated intrauterine device (IUD) or intrauterine system (IUS). Consideration should be given to the type of device being used, as there are higher failure rates quoted for certain types, e.g., steel or copper wire. * Condom with spermicidal foam/gel/film/cream/suppository. * Occlusive cap (diaphragm or