BETA PRIME: Phase I study of AdAPT-001 as monotherapy and combined with a checkpoint inhibitor in superficially accessible, treatment-refractory solid tumors
Santosh Kesari, Alberto Bessudo, Brian Gastman, Anthony P. Conley, Victoria Villaflor, Lisle M. Nabell, DeLisa Madere, Emma Chacon, Christina Spencer, Li Li, Christopher Larson, Tony Reid, Scott Caroen, Bryan Oronsky, Meaghan Stirn, Jeannie Williams, Minal Barve
Abstract
AdAPT-001 is an investigational therapy consisting of a replicative type 5 adenovirus armed with a TGF-β receptor-immunoglobulin Fc fusion trap, designed to neutralize isoforms 1 and 3 of the profibrotic and immunosuppressive cytokine, TGF-β. In preclinical studies with an immunocompetent mouse model, AdAPT-001 eradicated directly treated ‘cold’ tumors as well as distant untreated tumors, and, from its induction of systemic CD8+ T cell-mediated antitumor immunity, protected the mice from rechallenge with tumor cells. AdAPT-001 also sensitized resistant tumors to checkpoint blockade. This manuscript describes the rationale and design of the first-in-human phase I, dose-escalation and dose-expansion study of AdAPT-001 alone and in combination with a checkpoint inhibitor in adults with treatment-refractory superficially accessible solid tumors.