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

Abstract:

: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.

journal_name

Genomics

journal_title

Genomics

authors

O'Shannessy DJ,Bendas K,Schweizer C,Wang W,Albone E,Somers EB,Weil S,Meredith RK,Wustner J,Grasso L,Landers M,Nicolaides NC

doi

10.1016/j.ygeno.2017.04.006

subject

Has Abstract

pub_date

2017-07-01 00:00:00

pages

251-257

issue

3-4

eissn

0888-7543

issn

1089-8646

pii

S0888-7543(17)30029-0

journal_volume

109

pub_type

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