343 Multiomic biomarker signatures identify subsets of patients who may benefit from either nivolumab or sotigalimab in combination with chemotherapy in metastatic pancreatic cancer

Background Gemcitabine/nab-Paclitaxel (GnP) is a standard of care regimen for first-line metastatic pancreatic ductal adenocarcinoma (PDAC) and has 1-year overall survival (OS) rate approximately 35%. There an urgent need novel therapeutics precision medicine approaches in PDAC. PRINCE, randomized phase 2 trial, reported increased OS relative to historical data, patients treated with nivolumab (nivo)/GnP (57.3%, p = 0.007, n=34) sotigalimab (sotiga) (APX005M; CD40 agonist)/GnP (48.1%, 0.062, n= 36). Methods To investigate immune modulatory pharmacodynamic (PD) effects nivo or sotiga combination GnP we used several orthogonal minimally invasive, blood-based biomarker technologies. Immune population profiles were evaluated by CyTOF features T cell phenotype function multicolor flow cytometry. Soluble proteins predefined panels using the Olink platform (Immuno-oncology (IO) Response) along unbiased mass spectrometry proteomic approach (Biognosys) that identified circulating soluble significance. Results Relative baseline, who received nivo/GnP had numerically frequencies proliferating, activated CD8+ CD4+ effector memory cells circulation across multiple timepoints. These also significantly levels associated type II interferon responses migration activation, as well decreased immunomodulatory proteins.Patients sotiga/GnP expression co-stimulatory molecule CD86 on conventional dendritic cells. concentrations mature antigen presenting cells, activation helper B monocytes. Significant increases type-1 cell-mediated immunity decreases immunosuppressive factors observed both arms. defined ≤ 0.05, log2 fold change ≥ 0.5 (Olink) Sparse PLS discriminant analysis was zero threshold (Biognosys). Conclusions This study first use multiomic invasive PDAC demonstrate PD modulation immunotherapy/chemotherapy combinations. Orthogonal assays elicit unique are consistent their distinct mechanisms action. data suggest signatures may identify subsets benefit from immunotherapy/chemo Moreover, results these analyses will support early clinical development decisions. Acknowledgements We extend our gratitude patients, families, investigators, site staff members making this trial possible. would like thank Sultan Nawabi at Parker Institute Cancer Immunotherapy (PICI) operations leadership trial. Bristol Myers Squibb (BMS) Apexigen collaboration drugs. The funded Research Institute, BMS PICI. Trial Registration NCT03214250 Ethics Approval approved University Pennsylvania Institutional Review Board; Federalwide assurance #00004028.