Biomarker analysis of a randomized, placebo-controlled, double-blind, multicenter phase II trial of intravenous RO5137382/GC33 at 1600 mg Q2W in previously treated patients with unresectable advanced or metastatic hepatocellular carcinoma (HCC) (NCT01507168).

e15090 Background: Glypican-3 (GPC3) is an oncofetal protein frequently expressed in HCC. GC33 is a humanized monoclonal antibody against GPC3. Preclinical studies suggested that GC33 triggers antibody-dependent cytotoxicity (ADCC) against GPC3 expressed HCC. Methods: This is a double-blinded randomized placebo-controlled trial comparing placebo with GC33 with a primary endpoint of Progression Free Survival (PFS). 185 patients were assigned into three cohorts based on GPC3 IHC status: A (GPC3 2/3+), B (GPC3 1+) and C (GPC3 0). Tumor assessment was based on RECIST criteria. Biomarkers analyzed were: tumor and circulating GPC3, blood immune cell subtypes, functional marker expression of NK cells, blood ADCC activity, tumor CD16, FcγRIIIa polymorphism F158V and tumor gene expression. Results: CD16 (FcγRIIIa) protein expression in peripheral blood cells was identified as a potential predictive biomarker for GC33 efficacy, since patients with CD16 values above the median appear to benefit from GC33 treatment (...