PF-08046054

PF-08046054 (formerly known as SGN-PDL1V) is an investigational antibody-drug conjugate (ADC) targeting Programmed Cell Death Ligand 1 (PD-L1). Developed by Pfizer following its acquisition of Seagen, the molecule consists of a humanized anti-PD-L1 monoclonal antibody conjugated to the microtubule-disrupting cytotoxic payload monomethyl auristatin E (MMAE) via a protease-cleavable maleimidocaproyl-valine-citrulline (mc-vc) linker. It typically maintains a drug-to-antibody ratio (DAR) of 4. The ADC is designed to selectively deliver MMAE to PD-L1-expressing tumor cells, where it is internalized and released to induce cell cycle arrest and apoptosis. Beyond direct cytotoxicity, PF-08046054 exerts antitumor activity through bystander killing of neighboring cells and the induction of immunogenic cell death. It is currently being evaluated in the Phase 3 PADLINK-005 trial for patients with previously treated PD-L1-positive non-small cell lung cancer (NSCLC) and is also under investigation for other solid tumors, including head and neck squamous cell carcinoma (HNSCC).