Abstract 3503: A method for quantifying soluble folate receptor 1 in IMGN853 0401 clinical trial patients.

Abstract

Abstract IMGN853, an antibody-“drug” conjugate (ADC), consists of a human folate receptor 1 (FOLR1)-binding monoclonal antibody, M9346A, conjugated to the maytansinoid, DM4, via the cleavable sulfo-SPDB linker. A phase I clinical study has been initiated to identify the maximum tolerated dose, safety, pharmacokinetics (PK), and preliminary efficacy of IMGN853 in patients with FOLR1-positive tumors, including ovarian cancer, non-small cell lung cancer, and other epithelial malignancies. The levels of soluble FOLR1 antigen (sFOLR1) in plasma may vary depending on factors such as tumor antigen expression level, tumor type, and disease stage, and may affect the PK of IMGN853and response to treatment. Previously reported studies describing the detection of sFOLR1 in patient samples are limited and not quantitative. The aim of this study was to develop a sandwich ELISA to quantify levels of sFOLR1 present in plasma samples from cancer patients for use as a potential biomarker of IMGN853 PK and/or clinical response. A panel of murine anti-FOLR1 antibodies was generated at ImmunoGen by standard hybridoma technology. Two clones were chosen for use as capture (FR1-9) and detector (FR1-13) antibodies in the ELISA due to their high affinity and ability to bind to FOLR1 even in the presence of IMGN853 or the FOLR1 ligand, folate. The extracellular domain of FOLR1 fused to murine IgG2a Fc region (FOLR1-Fc) was used as a reference standard. A sandwich ELISA was developed using FR1-9 antibody to capture sFOLR1 from patient plasma, and bound sFOLR1 was detected using biotinylated FR1-13 antibody and streptavidin-HRP with TMB as the substrate. The ELISA was used to quantify sFOLR1 in ovarian carcinoma patient plasma using a reference standard curve generated with FOLR1-Fc antigen. A robust sandwich ELISA was developed to quantify sFOLR1 in patient plasma. The quantitation range of the assay was determined to be 0.2 to 90 nanomolar. Coated plates stored frozen from 0-14 days and protein reagents freeze-thawed over two cycles gave repeatable results. The ELISA was able to detect sFOLR1 in 5 of 10 ovarian cancer patient plasma samples, where the levels of detectable sFOLR1 ranged from 0.7-31 nM. This ELISA is considered suitable to quantify levels of sFOLR1 in patients enrolled in the phase 1 trial over the course of IMGN853 treatment, and resulting data will be assessed for correlations with IMGN853 PK and with clinical response. Citation Format: Nathan Testa, Laura Bartle, Olga Ab, Judy Cheng, Gillian Payne, Robert J. Lutz, Ben Wolf, Christina Carrigan. A method for quantifying soluble folate receptor 1 in IMGN853 0401 clinical trial patients. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3503. doi:10.1158/1538-7445.AM2013-3503