Population Pharmacokinetic Modeling of Certepetide in Human Subjects With Metastatic Pancreatic Ductal Adenocarcinoma.

Certepetide (aka LSTA1 and CEND-1) is a novel cyclic tumor-targeting internalizing arginyl glycylaspartic acid peptide being developed to treat solid tumors. Certepetide is designed to overcome existing challenges in treating solid tumors by delivering co-administered anticancer drugs into the tumor while selectively depleting immunosuppressive T cells, enhancing cytotoxic T cells in the tumor microenvironment, and inhibiting the metastatic cascade. A population pharmacokinetic (PK) analysis was conducted to characterize the concentration-time profile of patients with metastatic exocrine pancreatic cancer receiving certepetide in combination with nab-paclitaxel and gemcitabine, and to investigate the effects of clinically relevant covariates on PK parameters. The PK of certepetide was characterized by a 2-compartment model with linear elimination and a proportional residual error structure. Body weight and baseline creatinine clearance (CrCL) were found to have statistically significant effects on central and peripheral volume (Vc and Vp) and clearance (CL) parameters, respectively, during model development and were included as covariate effects in the final PK model. Forest plots demonstrated a potentially clinically meaningful impact of high body weight (100 kg) on certepetide exposure (steady-state maximum concentration [C_max,ss] and area under the concentration-time curve [AUC_ss]), as well as low and high CrCL (50 and 150 mL/min) on AUC_ss. Exposure predictions illustrated a relationship between certepetide exposure (AUC_ss) and renal function, with increasing exposure and decreasing CL of certepetide observed with worsening renal function. Modeling will strengthen the understanding of certepetide's PKs and will inform dose optimization in ongoing drug development activities.