P2.01-78 Validation of InVisionFirst ctDNA NGS Profiling via ddPCR Testing in Patients with Non-Small Cell Lung Cancer (NSCLC)

Abstract

Tumor tissue based molecular profiling is widely utilized to guide therapy in advanced NSCLC and recently, ctDNA assays have been developed to detect actionable alterations in a non-invasive manner. However, there are frequent reports of discordance between analysis platforms and here we compare the Inivata NGS ctDNA assay with ddPCR based ctDNA analysis and tissue NGS sequencing in patients with advanced NSCLC. InVisionFirst (Inivata) is a ctDNA NGS assay for detection of genomic alterations in 36 genes commonly mutated in NSCLC and other cancer types. A cohort of 52 patients underwent ctDNA analysis by InVisionFirst and were tested in a blinded manner for 4 actionable gene alterations (EGFR L858R and Ex19del, KRAS G12C and G12D) and 30 of the cohort also had testing for 5 additional alterations (EGFR T790, EML4-ALK fusions, ROS1 fusions, KRAS G12V and BRAF V600E) at one of two independent ddPCR laboratories. Finally, tissue analysis by NGS was available in 21 patients to arbitrate any discordance between the results of the 2 liquid biopsy techniques. Across the 9 specific genetic alterations investigated by both ctDNA platforms, 26 alterations were detected by the InvisionFirst platform and 23 were detected by the ddPCR platforms. The overall concordance of gene alterations was 98.5% (320/342) with positive agreement of 95.5% and negative agreement of 98.8%. Discordance was observed in 6 detected gene alterations, with 1 EML4-ALK fusion, 1 EGFR exon19 deletion and 2 KRAS G12Cs being detected by InVisionFirst but not by ddPCR, and 1 EGFR L858R and 1 KRAS G12D detected by ddPCR but not InVisionFirst. One G12C, the EML4-ALK, and the L858R alteration were confirmed by tissue NGS. The KRAS G12D was not confirmed by tissue NGS. No tissue was available to examine for the detection of the EGFR exon 19 deletion or the other KRAS G12C mutation. All other results were concordant. This study in NSCLC patients demonstrates excellent concordance of the InVisionFirst ctDNA NGS assay with ddPCR based ctDNA analysis via blinded independent laboratories. The excellent sensitivity and specificity support the use of the InVisionFirst assay as a non-invasive “liquid biopsy” for molecular profiling.