Genomic characterization of resectable pancreatic ductal adenocarcinoma (r-PDAC) on the NeoPancONE trial.

774 Background: The optimal approach in r-PDAC remains unclear. Perioperative Modified FOLFIRINOX (mFFX) is increasingly used yet we lack biomarkers to guide this approach. NeoPancONE demonstrated GATA6 high expression at baseline and classical RNA subtype on resection tissue in pts receiving perioperative mFFX was associated with a trend toward improved EFS and OS. Low GATA6/basal-like predicts early disease progression and poor outcomes 1 . We now report on additional transcriptome and genomic subtypes identified in the NeoPancONE resection specimens. Methods: Patients with r-PDAC were enrolled following central review and underwent an EUS FNB for central analysis of baseline GATA6 by in-situ hybridization (ISH). Surgical resection specimens were processed in each centre and fresh frozen tumor tissue was transferred for central whole genome and transcriptome sequencing (WGTS) following laser capture microdissection. WGTS reports annotated mutations, copy number alterations, mutational signatures, and structural variant patterns. KRAS allelic states were reported with major imbalances in mutant KRAS (KRAS maj ) defined as mutant: Wildtype (WT) copy number ≥3. RNA transcriptomic subtypes (classical vs. basal-like) were classified by PurIST. We report a descriptive and survival analysis of the genomic subgroups. Results: Of the 84 enrolled baseline GATA6 ISH was analysed in 74 (88%); 81% high, 19% low and 73 (87%) proceeded to surgery. PurIST subtyping was available in 51 (70%) of resections; 86% classic, 14% basal. Spearman correlation coefficient between GATA6 ISH and RNA subtype = 0.51 (p