PF-07104091 + palbociclib + letrozole

PF-07104091 + palbociclib + letrozole is an investigational, three-drug combination therapy under clinical evaluation for the treatment of advanced or metastatic hormone receptor-positive (HR+), HER2-negative breast cancer and other solid tumors. The regimen combines PF-07104091, a first-in-class, selective cyclin-dependent kinase 2 (CDK2) inhibitor; palbociclib, a well-established CDK4/6 inhibitor; and letrozole, an aromatase inhibitor that suppresses estrogen synthesis. This combination aims to overcome resistance mechanisms seen with prior CDK4/6 inhibition by targeting multiple cell cycle regulators alongside endocrine therapy. Early-phase clinical trials are assessing safety, tolerability, pharmacokinetics, and preliminary anti-tumor activity in heavily pretreated patient populations[2][5][7][9].