Increased Cd73 And Reduced Ifng Signature Expression In Relation To Response Rates To Anti-Pd-1(L1) Therapies In Egfr-Mutant Nsclc.

11505Background: Anti-PD-1(L1) therapies appear to be less efficacious in NSCLC patients whose tumors have EGFR activating mutations, but the underlying mechanism is poorly understood. We investigated the relationship between Methods: Flow cytometry and/or quantitative PCR were used to evaluate genes and proteins in five NSCLC EGFR mt cell lines and 6 wt lines. Anti-EGFR TKIs gefitinib and osimertinib were used at concentrations ranging from 0.001-100uM; EGF was used at 50 ng/mL. CP1108/NCT01693562 was a nonrandomized phase 1/2 trial evaluating durvalumab (10 mg/kg Q2W) in advanced NSCLC. As of 24OCT16, 304 previously treated patients in CP1108 were enrolled. RNA sequencing was conducted on available tumor specimens from 97 patients in CP1108. CP1108 and TCGA were separated by EGFR status for genomic comparisons. Results: Median CD73 expression was increased 10-fold in EGFR mt NSCLC cell lines (n = 5) compared to wt cell lines (n = 6). EGF induced CD73 protein levels 5-40-fold in 3/6 EGFR wt lines. There ...