Alpelisib, Fulvestrant and Dapagliflozin for the Treatment of HR+, HER2 -, PIK3CA Mutant Metastatic Breast Cancer

Inclusion Criteria: 1. Patients \> 18 years old with stage IV or locally advanced, unresectable Stage III breast cancer that is: 1. ER and/or PR positive by local laboratory evaluation 2. HER2 negative as defined by: either IHC status of 0, 1+ ; IHC of 2+ with FISH negative by ASCO/CAP guidelines. 2. If female, post-menopausal status as defined by 1. Prior bilateral oophorectomy 2. Age \> 60 3. Age \<60 and amenorrheic for 12 or more months in the absence of chemotherapy, tamoxifen, toremifene; or ovarian suppression and Follicle-stimulating Hormone (FSH) and estradiol in the postmenopausal range per local normal range. 4. Current use of LHRH agonist for ovarian suppression and estradiol and FSH documented in the post-menopausal range. 3. PIK3CA activating mutation identified by a either in a CLIA certified tumor genomic assay or ctDNA assay. 4. Patients may be: 1. relapsed with documented evidence of progression while on (neo) adjuvant endocrine therapy or within 12 months from completion of (neo)adjuvant endocrine therapy with no treatment for metastatic disease 2. relapsed with documented evidence of progression more than 12 months following/completion of (neo)adjuvant endocrine therapy and then subsequently progressed with documented evidence of progression while on or after only one line of endocrine therapy for metastatic disease 3. newly diagnosed advanced breast cancer, then relapsed with documented evidence of progression while on or after only one line of endocrine therapy 4. Prior endocrine treatment must have included a CDK4/6 inhibitor 5. ECOG performance status 0-2 6. Patient has adequate bone marrow and organ function as defined by the following laboratory values: 1. Absolute neutrophil count ≥ 1.0 × 109/L 2. Platelets ≥ 75 × 109/L 3. Hemoglobin ≥ 8.0 g/dL 4. Calcium (corrected for serum albumin) and magnesium within normal limits or ≤ grade 1 according to NCI-CTCAE version 4.03 if judged clinically not significant by the investigator 5. Potassium within normal limits, or corrected with supplements 6. Creatinine Clearance 35 ≥ mL/min using Cockcroft-Gault formula 7. In absence of liver metastases, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3.0 × ULN. If the patient has liver metastases, ALT and AST ≤ 5 × ULN 8. Total bilirubin \< ULN except for patients with Gilbert's syndrome who may only be included if the total bilirubin is ≤ 3.0 × ULN or direct bilirubin ≤ 1.5 × ULN≤ 7. Fasting plasma glucose (FPG) ≤ 200 and Glycosylated Hemoglobin (HbA1c) ≤ 6.5% 8. Fasting Serum amylase ≤ 2 × ULN 9. Fasting Serum lipase ≤ ULN Exclusion Criteria: 1. Patient has not recovered from all toxicities related to prior anticancer therapies to NCI CTCAE version 4.03 Grade ≤1. Exception to this criterion: patients with any grade of alopecia are allowed to enter the study. 2. Patient with symptomatic visceral disease or any disease burden that makes the patient ineligible for endocrine therapy per the investigator's best judgment. 3. Patients with Type I diabetes or history of diabetic ketoacidosis 4. Patient has received prior treatment with chemotherapy in the metastatic setting, fulvestrant, any PI3K, mTOR or AKT inhibitor 5. Patient has a known hypersensitivity to alpelisib or fulvestrant, or to any of the excipients of alpelisib or fulvestrant. 6. Patient is concurrently using other anti-cancer therapy. 7. Patient has had surgery within 14 days prior to starting study drug or has not recovered from major side effects of surgery. 8. Patient has central nervous system (CNS) involvement that does not meet ALL of the following criteria: * completed prior therapy (including radiation and/or surgery) for CNS metastases ≥ 14 days prior to the start of study and * CNS tumor is clinically stable at the time of screening and * patient is not receiving steroids and/or enzyme inducing anti-epileptic medications for brain metastases 9. Patient has impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of the study drugs (e.g., ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel resection) 10. Patient is following a ketogenic diet and unwilling to change diet. 11. Patient has any other concurrent severe and/or uncontrolled medical condition that would, in the investigator's judgment, contraindicate patient participation in the clinical study. 12. Patient has currently documented pneumonitis (the chest CT scan performed at baseline for the purpose of tumor assessment should be reviewed to confirm that there are no relevant pulmonary complications present). 13. Patient is currently receiving or has received systemic corticosteroids 7 days prior to starting study drug, or who have not fully recovered from side effects of such treatment. Note: The following uses of corticosteroids are permitted: single doses, topical applications (e.g., for rash), inhaled sprays (e.g., for obstructive airways diseases), eye drops or local injections (e.g., intra-articular). 14. Sexually active males unless they are sterilized (at least 6 months prior to screening) or use a condom during intercourse while taking drug and for at least 8 months after stopping alpelisib and/or fulvestrant. . 15. Participation in a prior investigational study within 14 days prior to the start of study treatment or within 5 half-lives of the investigational product, whichever is longer. 16. Not able to understand and to comply with study instructions and requirements. 17. History of acute pancreatitis within1 year of screening or past medical history of chronic pancreatitis.