alpelisib + imlunestrant

Alpelisib + imlunestrant is an investigational combination therapy for the treatment of advanced or metastatic hormone receptor–positive (HR+), HER2-negative breast cancer. Alpelisib is a small molecule inhibitor of phosphatidylinositol 3-kinase alpha (PI3Kα), targeting the PIK3CA pathway, which is frequently mutated in HR+ breast cancer. Imlunestrant is a next-generation oral selective estrogen receptor degrader (SERD) that binds to and induces degradation of the estrogen receptor, thereby inhibiting estrogen-driven tumor growth—including in tumors with ESR1 mutations. The combination aims to overcome resistance mechanisms to endocrine therapy by simultaneously blocking both PI3K signaling and estrogen receptor activity. Early-phase clinical trials have shown manageable safety profiles and preliminary antitumor activity for this combination in patients previously treated with CDK4/6 inhibitors and other endocrine therapies[1][2][6][7].