Clinicogenomic real-world data analysis of patients (pts) with KRAS G12C-mutant advanced non-small cell lung cancer (aNSCLC) from the natural history cohort of the Blood First Assay Screening Trial (BFAST).

9023 Background: BFAST (NCT03178552) is a global, multicohort trial of targeted therapies or cancer immunotherapy (CIT) in treatment (tx)-naive aNSCLC. Pts are screened for the study using comprehensive blood-based next-generation sequencing (NGS). In the BFAST natural history cohort, data were collected for pts who received tx or care outside the study’s interventional cohorts. Here, we analyzed the subset of pts whose tumors have KRAS G12C mutations (mut). Methods: Pts eligible for blood-based NGS screening had unresectable aNSCLC, ECOG PS 0-2 and no prior systemic tx for aNSCLC. Pts without tissue samples were eligible. Key genomic and molecular features, including bTMB, PD-L1 and ctDNA concentration; cancer tx; tx response and survival data were collected and analyzed in an exploratory analysis. Results: In the full BFAST screening population through December 2020 (N = 5917), 23% of pts had tumors with any KRAS mut; 9% were KRAS G12C. Pts were enrolled in the natural history cohort from October 2018 to October 2020 (n = 1017); 63 pts had tumors with KRAS G12C mut. Median age was 68 y, 59% were male, 86% had ECOG PS 0-1 and 84% had non-squamous histology. Co-mut in TP53 (60%) and STK11 and/or KEAP1 (25%) were detected; 8% of pts had bTMB ≥16. High PD-L1 expression per local testing was reported in 32% of pts; 38% were not tested. Among pts with 1L tx (n = 50), 50%, 28% and 20% received chemo, CIT or CIT + chemo, respectively, with real-world response rates (CR/PR per physician assessment) of 20%, 29% and 30%, respectively. Of the 13 pts (21%) without documented 1L tx, 7 died ≤3 mo from enrollment. Median OS was 14 mo overall, with differences found between key genomic subsets (Table). Conclusions: BFAST is the first study to identify KRAS G12C mut using blood-based NGS and describe the natural history, clinical characteristics and genomic landscape of this pt subset. Up to 21% of pts may not receive 1L tx. Pts with TP53 co-mut appear to have favorable outcomes, while those with STK11 and/or KEAP1 co-mut appear to have inferior outcomes vs pts without these mut. The lack of PD-L1 testing in many pts indicates a lack of tissue for comprehensive tissue testing, highlighting a potential benefit of blood-based detection of biomarkers, including KRAS G12C. Clinical trial information: NCT03178552. [Table: see text]