Population Pharmacokinetics (PK) and Exposure-Efficacy Analyses of Nivolumab in Subjects with Advanced Hepatocellular Carcinoma (HCC)

Authors: Wang X, Ludwig EA, Passarell C, Boone B, Baakili A, Dela Cruz C, Roy A, Hruska M
Conference: ACoP
Keywords: exposure-efficacy analyses, hepatocellular carcinoma (HCC), nivolumab, Oncology, population pharmacokinetics
Division: Clinical Pharmacology and Pharmacometrics (CPP)

Introduction

  • Nivolumab is a fully human immunoglobulin G4 (IgG4) monoclonal antibody (mAb) that selectively binds to the programmed death-1 (PD-1) membrane receptor1
  • PD-1 is a negative regulatory molecule expressed by activated T and B lymphocytes. Binding of PD-1 to its ligands, programmed death-ligand 1 (PD-L1) and 2 (PD-L2), results in the downregulation of lymphocyte activation1
  • Inhibition of the interaction between PD-1 and its ligands promotes immune responses and antigen-specific T-cell responses to both foreign antigens as well as self antigens1
  • Nivolumab 3 mg/kg, or an equivalent 240-mg dose, once every 2 weeks (Q2W) was approved for melanoma, non-small cell lung cancer (NSCLC), renal cell carcinoma, head and neck cancer, classical Hodgkin lymphoma, urothelial carcinoma, and colorectal cancer in the United States and other countries2
  • Nivolumab also demonstrated durable response and disease stabilization in patients with advanced HCC who have been previously treated with sorafenib in a phase 1/2 study (CA-209040), and has been recently approved for this indication by the US FDA

Eighth American Conference on Pharmacometrics (ACoP) Annual Meeting: October 15-18, 2017, Fort Lauderdale, FL

By Wang X, Elizabeth A Ludwig, Caroline Passarell, Boone B, Baakili A, Dela Cruz C, Roy A, Hruska M