Identification of a predictive biomarker for patritumab (P), an anti-HER3 monoclonal antibody, in advanced NSCLC.

e19016 Background: HER3, an ErbB receptor with 6 docking sites for PI3K, is implicated in resistance to cancer treatment. P is a fully human mAb specific to HER3. Heregulin (HRG) is the ligand for HER3. In preclinical studies, HRG expression predicted sensitivity to P (Schneider et al., Yonesaka et al. ASCO 2014). P, in combination with erlotinib vs. erlotinib alone, was assessed in a randomized Ph2 study in advanced NSCLC (HERALD, von Pawel et al., ASCO 2014). Methods: Based on preclinical data after HERALD study initiation, HRG was identified as the primary predictive biomarker hypothesis for P clinical benefit prior to unblinding (prospective), albeit after subject enrollment (retrospective). Various methods were explored to measure HRG protein or mRNA in FFPE tissue, and a validated quantitative PCR assay for HRG mRNA measurment was developed. The median delta threshold cycle ΔCt value was specified as the cut-off for HRG high/low, prior to study unblinding. Other biomarkers were also measured, but no...