Population pharmacokinetics of MYL-1401O (a trastuzumab biosimilar) and reference trastuzumab (Herceptin®) in patients with HER2-positive metastatic breast cancer

Authors: Owen JS, Rackley R, Liu M, Fuentes-Alburo A, Idris T, Loganathan S, Barve A, Waller CF, Rugo HS
Conference: San Antonio Breast Cancer Symposium (SABCS)
Keywords: breast cancer, HER2 receptor, MYL-1401O, PopPK, population pharmacokinetics, trastuzumab
Division: Clinical Pharmacology and Pharmacometrics (CPP)

Background

  • Mylan trastuzumab (MYL-1401O) is a biosimilar to trastuzumab (Herceptin®)
  • A multicenter, double-blind, randomized phase 3 study (HERITAGE) compared the efficacy, safety, population pharmacokinetics (Pop PK) and immunogenicity of MYL-1401O and Herceptin® in patients with HER2-positive metastatic breast cancer (MBC)
  • In the HERITAGE trial, patients were randomized 1:1 to receive either MYL1401O or Herceptin®, in combination with taxane, every 3 weeks for 24 weeks (8 cycles) followed by monotherapy until unacceptable toxicity, disease progression, or early discontinuation
  • Results of the Pop PK analysis of the HERITAGE trial are presented here.

Study Objectives

  • The primary objectives of the Pop PK analysis were:
  • To compare the Pop PK–derived area under the curve (AUC), maximum serum concentration (Cmax), clearance (CL), volume of distribution (Vd), and terminal elimination half-life (t1/2) profiles of MYL-1401O and Herceptin®
  • To perform an exploratory assessment of the impact of shed extracellular domain (ECD) fragments of the HER2 receptor (HER2/ECD) on PK parameters.

By Joel Owen, Russell Rackley, Mark Liu, Adolfo Fuentes-Alburo, Tazeen Idris, Subramanian Loganathan, Abhijit Barve, Cornelius F. Waller, Hope S. Rugo

San Antonio Breast Cancer Symposium (SABCS) 2020 Annual Meeting, 8-12 December, 2020.