Correlation of FCGRT genomic structure with serum immunoglobulin, albumin and farletuzumab pharmacokinetics in patients with first relapsed ovarian cancer

Genomics. 2017 Jul;109(3-4):251-257. doi: 10.1016/j.ygeno.2017.04.006. Epub 2017 Apr 25.


Farletuzumab (FAR) is a humanized monoclonal antibody (mAb) that binds to folate receptor alpha. A Ph3 trial in ovarian cancer patients treated with carboplatin/taxane plus FAR or placebo did not meet the primary statistical endpoint. Subgroup analysis demonstrated that subjects with high FAR exposure levels (Cmin>57.6μg/mL) showed statistically significant improvements in PFS and OS. The neonatal Fc receptor (fcgrt) plays a central role in albumin/IgG stasis and mAb pharmacokinetics (PK). Here we evaluated fcgrt sequence and association of its promoter variable number tandem repeats (VNTR) and coding single nucleotide variants (SNV) with albumin/IgG levels and FAR PK in the Ph3 patients. A statistical correlation existed between high FAR Cmin and AUC in patients with the highest quartile of albumin and lowest quartile of IgG1. Analysis of fcgrt identified 5 different VNTRs in the promoter region and 9 SNVs within the coding region, 4 which are novel.

Keywords: Albumin; Farletuzumab; FcRn; Fcgrt; IgG; Monoclonal antibody; Neonatal Fc receptor; Ovarian cancer; Pharmacokinetics.

MeSH terms

  • Albumins / analysis
  • Albumins / pharmacokinetics*
  • Antibodies, Monoclonal, Humanized / pharmacokinetics*
  • Antibodies, Monoclonal, Humanized / pharmacology
  • Antibodies, Monoclonal, Humanized / therapeutic use
  • Clinical Trials, Phase III as Topic
  • Female
  • Histocompatibility Antigens Class I / genetics*
  • Humans
  • Immunoglobulin G / blood
  • Immunoglobulin G / metabolism*
  • Minisatellite Repeats
  • Neoplasm Recurrence, Local
  • Ovarian Neoplasms / drug therapy*
  • Ovarian Neoplasms / metabolism
  • Ovarian Neoplasms / pathology
  • Polymorphism, Single Nucleotide
  • Receptors, Fc / genetics*


  • Albumins
  • Antibodies, Monoclonal, Humanized
  • Histocompatibility Antigens Class I
  • Immunoglobulin G
  • Receptors, Fc
  • farletuzumab
  • Fc receptor, neonatal