Interleukin-12 anchored drug conjugate (tolododekin alfa) in patients with advanced solid tumors: Results of a first-in-human Phase 1 trial

Anchored immunotherapy is a novel approach for retaining high doses of drugs within the tumor microenvironment improving the therapeutic window . Tolododekin alfa is a first-in-class anchored drug conjugate in which IL-12 is linked to aluminum hydroxide. Safety and biologic activity was evaluated in a Phase 1 clinical trial in patients with accessible advanced solid tumors. The primary objectives were safety and tolerability. Secondary objectives included pharmacokinetics, pharmacodynamics, preliminary antitumor activity, and immunogenicity. Fifteen patients were enrolled and dosed at escalating doses of tolododekin alfa given by direct injection once every 3 weeks. There were no dose-limiting toxicities or treatment-related serious adverse events. PK/PD measurements demonstrated retention of drug in the tumor at all dose levels. Biologic activity was demonstrated by increased CD8+ T cells, PD-L1 expression, and prolonged pro-inflammatory gene expression. Nine patients (60%) achieved disease control. These findings support continued clinical development of tolododekin alfa. ClinicalTrials.gov registration: NCT06171750.