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ascorbate + durvalumab is an investigational combination therapy being evaluated for the treatment of early-stage, resectable non-small cell lung cancer (NSCLC). The regimen consists of pharmacological ascorbate (high-dose intravenous Vitamin C) and durvalumab (Imfinzi), a human monoclonal antibody targeting programmed cell death-ligand 1 (PD-L1). Pharmacological ascorbate acts as a pro-oxidant at millimolar concentrations, generating hydrogen peroxide that selectively induces oxidative stress and DNA damage in tumor cells. Durvalumab functions as an immune checkpoint inhibitor, blocking the interaction between PD-L1 and its receptors (PD-1 and CD80) to restore and enhance T-cell-mediated anti-tumor immunity. This combination is currently being studied in a 'window of opportunity' Phase 2 trial (NCT04051307) led by William Zeitler at the University of Iowa to assess its immunomodulatory effects and safety as a neoadjuvant therapy prior to surgical resection.
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