LOXO-783 + imlunestrant

LOXO-783 + imlunestrant is a combination therapy under clinical investigation for the treatment of breast cancer, particularly in patients with PIK3CA-mutated, estrogen receptor (ER)-positive, HER2-negative advanced or metastatic disease. - **LOXO-783** is a potent, highly mutant-selective, brain-penetrant allosteric inhibitor of *PI3K alpha* (phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha, encoded by the PIK3CA gene), specifically targeting mutant forms such as H1047R. - **Imlunestrant** (LY3484356, Inluriyo) is a next-generation, oral selective estrogen receptor degrader (SERD) that binds and induces degradation of the ER, including in ESR1 mutant tumors. Preclinical and clinical studies suggest that combining these agents increases efficacy over monotherapy in ER+/HER2–/PIK3CA-mutant models, possibly overcoming resistance due to ESR1 or PI3Kα mutations[2][5][7]. This combination is being evaluated in phase 1 studies for safety, tolerability, pharmacokinetics, and preliminary antitumor activity in breast cancer and other solid tumors[1][4][5].