LOXO-783 + paclitaxel

This is a combination regimen of **LOXO-783**, an orally available, brain-penetrant, allosteric, and highly selective inhibitor of phosphoinositide 3-kinase alpha (PI3Kα) with activity specifically against the PI3Kα H1047R mutation, and **paclitaxel**, a microtubule-stabilizing chemotherapeutic agent. LOXO-783 is designed to spare wild-type PI3Kα in healthy tissue, aiming to reduce typical PI3K inhibitor toxicities such as hyperglycemia. The combination is being clinically evaluated for patients with advanced breast cancer and other solid tumors harboring PIK3CA H1047R mutations. Paclitaxel disrupts microtubule function and inhibits cell division, while LOXO-783 targets the oncogenic driver mutation to suppress tumor cell proliferation. This drug combination is under investigation primarily for HR+, HER2-, PI3Kα H1047R-mutant breast cancer, showing preliminary clinical activity but notable gastrointestinal side effects, especially diarrhea[1][3][4][5].