alpelisib + evexomostat + fulvestrant

This is a combination therapy consisting of three drugs: - **Alpelisib** is a selective inhibitor of phosphatidylinositol 3-kinase alpha (PI3Kα), used to target tumors with PIK3CA mutations. It is approved for use in hormone receptor-positive (HR+), HER2-negative advanced or metastatic breast cancer. - **Evexomostat** (SDX-7320) is a polymer-drug conjugate of a novel small molecule methionine aminopeptidase 2 (MetAP2) inhibitor. It has demonstrated the ability to reduce alpelisib-induced hyperglycemia and shows synergistic anti-tumor activity independent of glucose or insulin changes. Evexomostat also improves insulin resistance and metabolic parameters in patients at risk for hyperglycemia. - **Fulvestrant** is an estrogen receptor antagonist that binds competitively to estrogen receptors on tumors and other tissues. The triplet therapy aims to improve anti-tumor efficacy while mitigating the common side effect of hyperglycemia associated with alpelisib by including evexomostat. This combination is being studied primarily in postmenopausal women with HR+, HER2-, PIK3CA-mutated advanced or metastatic breast cancer who have progressed after endocrine therapy plus CDK4/6 inhibitors[1][5][7][9].