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-TUMOR) delivery is being widely explored for novel anti-cancer agents. This route is anticipated to result in high tumor 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 predictability of human pharmacokinetics following I-TUMOR delivery.In this publication, we present a case study wherein human systemic PK of a novel agent administered intra-tumorally 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-TUMOR bioavailability, human plasma PK profile was simulated. The projected 30 min concentrations and AUC(0-6h) were within 1.9-2.5 fold and 1-1.4 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-TUMOR dosing. The results from this study indicate that similar approaches can be used to project the human PK of other I-TUMOR agents.