Our EGFRvIII TAT consists of a humanized EGFRvIII monoclonal antibody, a proprietary bifunctional chelate, and the alpha-emitting radionuclide, actinium-225 (225Ac). In vivo biodistribution and efficacy of our EGFRvIII TAT was evaluated in two aggressive orthotopic EGFRvIII-expressing GBM patient-derived xenograft models...we show that combined treatment of [225Ac]-anti-EGFRvIII with the standard of care (SoC), external beam radiation plus temozolomide, resulted in a significant survival advantage (>1.7-fold) compared to TAT or SoC therapy alone. Collectively, these results demonstrate that [225Ac]-anti-EGFRvIII is a highly selective and potent therapeutic for GBM which holds great potential as both a single-agent and in combination with SoC.