capivasertib + evexomostat + fulvestrant

This is a combination therapy consisting of three agents: - **Capivasertib** is an oral small molecule inhibitor targeting AKT kinases. It blocks the PI3K/AKT signaling pathway, which is frequently activated in hormone receptor-positive breast cancer due to mutations in PIK3CA, AKT1 or PTEN. Capivasertib has been shown to improve progression-free survival when combined with endocrine therapy such as fulvestrant. - **Evexomostat** (SDX-7320) is a polymer-conjugated inhibitor of methionine aminopeptidase 2 (MetAP2). It modulates metabolic and angiogenic pathways by irreversibly binding MetAP2, leading to improvements in insulin sensitivity and lipid profiles while inhibiting angiogenesis via suppression of bFGF and VEGF-C. Evexomostat is being developed specifically for cancer patients with metabolic complications such as obesity or insulin resistance. - **Fulvestrant** is a selective estrogen receptor degrader (SERD) that binds to estrogen receptors and accelerates their degradation, thereby blocking estrogen-driven tumor growth. The triplet combination aims to target multiple mechanisms involved in advanced hormone receptor-positive/HER2-negative breast cancer—blocking both the PI3K/AKT pathway and estrogen signaling while addressing metabolic dysfunctions that may contribute to tumor aggressiveness or treatment resistance[1][7][10].