1244 - Nanoray Pancreas: Biomarker Insights of NBTXR3 Activated by Radiotherapy (RT) for Locally Advanced or Borderline Resectable Pancreatic Cancer (LAPC or BRPC)

Purpose/Objective(s): Pancreatic ductal adenocarcinoma (PDAC) is characterized by radioresistance and poor outcomes, with few biomarker-driven treatment strategies. NBTXR3 is an injectable radioenhancer composed of functionalized hafnium oxide nanoparticles activated by RT with demonstrated safety and preliminary efficacy in a prospective phase I study in patients with LAPC or BRPC. The objective of this study was to investigate biomarker response to NBTXR3/RT (45 Gy in 15 fractions; BED 58.5 Gy10), including carbohydrate antigen 19-9 (CA19-9) and emerging plasma biomarkers previously associated with a PDAC migration signature, specifically tenascin C (TNC) and tissue factor pathway inhibitor (TFPI).

Materials/Methods: In this single institution phase I trial (NCT04484909), blood samples were obtained to assess CA19-9, TNC, and TFPI. Baseline biomarker levels and changes at first follow up after NBTXR3/RT were analyzed as continuous variables. Association between biomarkers and time-to-event outcomes, including local progression-free survival (LPFS), distant progression-free survival (DPFS), and overall survival (OS) were assessed using Cox proportional hazard regression modeling. Hazard ratios calculated for continuous variables; p<0.05 denotes significance.

Results: 22 patients [median age 63 (range 39 – 81), 54.5% female] enrolled between September 2020 and October 2025 had a median follow up for completed protocol therapy of 11.9 months (range 3 – 40.7). 72.7% of patients had elevated CA19-9 prior to treatment initiation, which normalized in 50% of those patients at the conclusion of chemotherapy/RT. Baseline TNC was 61.1 U/mL (range 28.0 – 144.8) with median change of -7.4 (range -71.7 – 45.7). Baseline TFPI was 31.4 U/mL (range 18.3 – 81.7) with median change of -5.1 (-45.7 – 20.4). Associations with LPFS, DPFS, and OS are summarized in the Table, with changes in CA19-9 and baseline TNC showing correlations with all three clinical outcomes.

Conclusion: Changes in CA19-9 and baseline TNC values may be associated with differences in survival in patients treated with NBTXR3/RT. Analysis of larger datasets for validation of the independent prognostic and potential predictive value of these biomarkers is ongoing.