PF-06804103

PF-06804103 is a site-specific antibody-drug conjugate (ADC) developed by Pfizer for the treatment of HER2-expressing solid tumors, including breast and gastric cancers. It consists of a monoclonal antibody targeting human epidermal growth factor receptor 2 (HER2), site-specifically conjugated via a protease-cleavable linker to an auristatin payload (Auristatin-0101, an analog of dolastatin 10). The design incorporates engineered cysteine residues for precise drug-antibody ratio and improved stability. The payload acts as a microtubule inhibitor, disrupting mitosis and inducing apoptosis in cancer cells. PF-06804103 demonstrated enhanced efficacy in preclinical models with both high and low HER2 expression, including activity against T-DM1-resistant tumors. Clinical development was discontinued after phase 1 trials due to strategic business decisions rather than safety concerns[1][3][4][6].