STK11/LKB1 co-mutations to predict for de novo resistance to PD-1/PD-L1 axis blockade in KRAS-mutant lung adenocarcinoma.

9016Background: Identification of molecular predictors of response to PD-1/PD-L1 inhibitors is critical in order to maximize their therapeutic potential. We previously reported that KRAS-mutant lung adenocarcinomas (LUAC) with co-occurring genetic events in STK11/LKB1(KL) or TP53 (KP) define subgroups with marked differences in immune contexture, including a paucity of CD8+ TILs in KL LUAC. Here, we assess clinical responses to PD-1/PD-L1 therapy in KL and KP subsets, with data assembled under the auspices of the SU2C/ACS Lung Cancer Dream Team. Methods: Patients (pts) with metastatic KRAS-mutant LUAC who received at least one cycle of PD-1/PD-L1 therapy, were alive for ≥14 days thereafter, and had available molecular profiling were identified retrospectively. Efficacy assessment was based on RECIST v1.1. PD-L1 expression was tested using 22C3 pharmDx or E1L3N IHC assays and quantified as percent of staining tumor cell membranes. Isogenic derivatives of the LKR10 KrasLA1/+ murine LUAC cell line with CRISP...