BIOM-03. COMPREHENSIVE GENOMIC AND IMMUNE PROFILING OF NON-SMALL CELL LUNG CANCER BRAIN METASTASES REVEALS LOW TUMOR INFLAMMATION AND ELEVATED CANCER TESTIS ANTIGEN BURDEN

Abstract BACKGROUND Non-small cell lung cancer (NSCLC) accounts for ~50% of brain metastases. We present the genomic and immune biomarker landscape a cohort with metastatic NSCLC to brain. METHODS analyzed metastases FFPE tissue (n=137; ages 40-85y (mean 65y), 52% female, 48% male) vs. primary sites (n=5533; 24-100+y 71y), 51% 49% advanced or patients comprehensive profiling, including PD-L1 IHC, tumor mutational burden (TMB), Tumor Immunogenic Signature (TIGS), Cell Proliferation (CP), Cancer Testis Antigen Burden (CTAB). RESULTS Genomic alteration (GA) frequency metastasis versus were similar among most frequently mutated genes except KRAS which was significantly higher (39.9% vs 25.5%, p< 0.0005). No significant differences observed TP53 (50.7% 50.2%), STK11 (11.5% 10.9%), CDKN2A (10.1% 7%), EGFR (8.0% 11.5%). expression all cases by IHC not different TPS 29.9% 26.3%); however, more likely be negative (TPS< 1%) (46.3% 33.3%, 0.005). Conversely, TMB in (12.9 10.2 muts/MB, 8x10-10), TMB-high (10 muts/Mb) (57.0% 33.5%, 3x10-8). Similarly, had proportion CTAB-high (68.6% 57.6%, p=0.01). The response score, TIGS, often weak (52.6% 34.0%, 9x10-6). CONCLUSION In NSCLC, lesions have larger antigen burden, increased CTAB, due privileged nature brain, is reflected lower TIGS scores positivity. Despite positivity, may potentially benefit from immunotherapy strategies given high CTAB.