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

Anchored immunotherapy is a novel approach for retaining drugs within the tumour microenvironment. Tolododekin alfa is a first-in-class anchored Interleukin 12 (IL-12) linked to aluminum hydroxide. Safety and biological activity were evaluated in a Phase 1 clinical trial in patients with accessible advanced solid tumours in Part 1 of a 3-part trial. The primary objectives are safety and tolerability as well as determination of the recommended dose for expansion (RDE). Secondary objectives include pharmacokinetics (PK), pharmacodynamics, preliminary antitumour activity, and immunogenicity. Exploratory analyses include serum and tissue biomarkers. Fifteen patients were enrolled at escalating doses of tolododekin alfa given by injection every 3 weeks. There were no dose-limiting toxicities or treatment-related serious adverse events. PK/Pharmacodynamic measurements demonstrate retention of drug in the tumour. Biological activity demonstrates increased CD8⁺ T cells, Programmed Cell Death Ligand 1 (PD-L1) expression, and prolonged pro-inflammatory gene expression. Nine patients (60%) achieved stable disease with one partial response. At a median follow-up of 5.2 months, the median duration of stable disease was 5.3 months (range 3.6-7.6 months). Median progression-free survival (PFS) was not estimable (NE) (95% CI, 2.57 months - NE). These findings support continued clinical development of tolododekin alfa. ClinicalTrials.gov registration: NCT06171750.