Fig. 4: Baseline ctDNA genomic analysis identifies prognostic biomarkers.
A A CLIA-approved 152-gene next generation sequencing (NGS) assay (Predicine CARETM) was used to perform ctDNA based genomic profiling on diagnostic &/or pre-treatment plasma samples from 30 cases in our clinical trial. Genomic profiling showed high rates of TP53 alterations and HER2 amplifications were identified in 76.7% of the cohort (23/30). B 56.7% of the cases in our cohort (17/30) have evidence of additional MAPK driver alteration in addition to HER2. Amplifications in the receptor tyrosine kinases (RTKs) including in EGFR, KRAS, MET, and FGFR1 are the most common additional MAPK alterations. Cases with additional MAPK alterations (MAPK Alt) have a significantly worse progression free C and overall survival D compared to those who’s tumors without additional MAPK alterations (MAPK Wild Type, WT). Patients with high tumor fraction (TF) at diagnosis, estimated using a combination of low pass whole genome sequencing (LP-WGS) using ichorCNA39 and somatic mutation allele frequencies in ctDNA NGS assay, display a significantly worse progression free E and overall survival F. P-value was calculated using two-tailed log rank test C–F. BRR Best radiographic response, CR Complete Response, PR Partial Response, SD Stable disease, PD Progressive disease.
