PF-06804103 + palbociclib + letrozole

PF-06804103 is an investigational antibody-drug conjugate (ADC) developed by Pfizer, designed to target human epidermal growth factor receptor 2 (HER2). It consists of a monoclonal antibody against HER2 site-specifically linked via a protease-cleavable linker to an auristatin payload (Auristatin-0101, an analog of dolastatin 10), which acts as a cytotoxic agent. The drug was engineered for enhanced stability, efficacy, and safety compared to earlier HER2-targeted ADCs such as T-DM1. In clinical studies, PF-06804103 demonstrated activity in both high and low HER2-expressing breast and gastric cancers and showed the ability to overcome resistance to T-DM1. Palbociclib is a small molecule inhibitor of cyclin-dependent kinases 4/6 (CDK4/6), while letrozole is an aromatase inhibitor; both are standard treatments for hormone receptor-positive breast cancer. The combination was studied in advanced or metastatic breast cancer patients with HER2 expression[3][5][7].