Predictive Effect of Spatial Protein Signature in Advanced Non-small Cell Lung Cancer Patients Treated with Bispecific Antibody (KN046) Immunotherapy

Background Immunotherapy, targeting programmed death ligand-1 (PD-L1) and cytotoxic T lymphocyte-associated antigen-4, has shown significant antitumor activity and favourable safety profile in patients with advanced non-small cell lung cancer (NSCLC), while predictive biomarkers remain largely unknown. Here, we investigated the predictive effect of spatial protein expression signature of KN046, a bispecific antibody (bsAb), as a treatment in advanced NSCLC patients. Methods Digital spatial profiling was used to investigate protein expression in both tumor and stroma areas of formalin-fixed paraffin-embedded sections at baseline. Regions of interests (ROIs) were recorded after tricolor fluorescence labeling. The geometric means of different protein expression of different response groups were combined to construct the tumor signature, the stroma signature and the tumor + stroma signature. The accurate score was determined by receiver operating characteristic curve and the area under the curve (AUC). Results Eight patients with partial response (PR) and nine with progressive disease (PD) were enrolled in the study. Among 133 ROIs, 14 proteins expressed differently between PR and PD groups (both P P P P P P