PF-08046037

PF-08046037 is an **investigational immune-stimulating antibody conjugate (ISAC)** currently in early clinical development for cancer therapy. It consists of a **humanized anti-PD-L1 monoclonal antibody** that serves primarily as a "docking site" to selectively deliver an **imidazoquinoline-based TLR7 agonist payload** into the tumor microenvironment, specifically to PD-L1-expressing antigen-presenting cells (APCs). The antibody is engineered with Fc domain mutations to reduce FcγR binding, minimizing off-target immune activation and enhancing safety. The TLR7 agonist payload activates endosomal Toll-like receptor 7 (TLR7) in APCs upon intracellular release, stimulating both innate and adaptive anti-tumor immune responses. A mannosidase-cleavable linker is used to attach the payload, providing stability in circulation and enabling specific payload release within mannosidase-rich endosomes of APCs. PF-08046037 is designed to overcome some limitations of standard anti-PD-L1 antibodies by combining precise tumor targeting with potent immune activation, aiming for improved cancer immunotherapy efficacy. Originally developed by Seagen and now owned and advanced by Pfizer, PF-08046037 is being studied as both monotherapy and in combination with sasanlimab in patients with advanced or metastatic malignancies, including non-small cell lung cancer, head and neck squamous cell carcinoma, melanoma, and pancreatic ductal adenocarcinoma[1][3][5][7][9].

Other names

PF 08046037PF08046037PF-08046037