Prospective prediction of plasma pharmacokinetics of a novel immune-modulating agent in cancer patients after intra-tumoral administration: translation from non-clinical species to humans

Intra-tumoral (I-TUMOUR) delivery is being widely explored for novel anti-cancer agents. This route is anticipated to result in high tumour concentrations leading to better efficacy and safety. Prediction of human systemic pharmacokinetics (PK) from non-clinical species facilitates understanding of pharmacokinetic-pharmacodynamic relationships, efficient dose selection, and risk assessment of novel drugs. However, there is limited knowledge on the predictability of human pharmacokinetics following I-TUMOUR delivery. In this publication, we present a case study wherein human systemic PK of a novel agent administered intra-tumourally was prospectively predicted and compared with observed human PK. Simple allometry was used to project the human clearance (10.5 mL/min/kg) and steady-state volume of distribution (1.4 L/kg) after intravenous (IV) dosing. Using these IV PK parameters and assuming rapid absorption and complete I-TUMOUR bioavailability, human plasma PK profile was simulated. The projected 30 min concentrations and AUC((0-6h)) were within 1.9 to 2.5-fold and 1 to 1.4-fold of the observed PK indicating a reasonable concordance between predicted and observed PK. To our knowledge, this is the first article that prospectively projected human pharmacokinetics after I-TUMOUR dosing. The results from this study indicate that similar approaches can be used to project the human PK of other I-TUMOUR agents.