LOXO-783 + anastrozole + exemestane + letrozole

LOXO-783 + anastrozole + exemestane + letrozole is an experimental combination regimen investigated for patients with advanced breast cancer and other solid tumors harboring a PIK3CA H1047R mutation. LOXO-783 is a potent, highly mutant-selective, brain-penetrant, allosteric inhibitor of phosphoinositide 3-kinase alpha (PI3Kα), designed to selectively inhibit the H1047R-mutated PI3Kα enzyme, thereby blocking key oncogenic signaling pathways in cancers driven by this mutation[2]. Anastrozole, exemestane, and letrozole are all aromatase inhibitors that act by inhibiting aromatase, thereby reducing estrogen production and hormone signaling in ER+ breast cancer. This combination aims to maximize anti-tumor efficacy while minimizing toxicity by targeting both oncogenic pathways and hormone-dependent proliferation[2][1].