Abstract A126: Tumor-informed ctDNA, ddPCR, CA19-9, and CEA to evaluate early treatment dynamics in patients with metastatic pancreatic cancer

Introduction Blood-based biomarkers may enable earlier assessment of treatment response than imaging in patients with metastatic pancreatic cancer. Tumor-informed circulating tumor DNA (ctDNA) approaches may be more sensitive, whereas tumor-naïve ctDNA profiling using KRAS mutations may offer a cheaper and faster alternative for most patients with PDAC. CA19-9 and CEA are also commonly used as tumor markers for PDAC treatment monitoring. We hypothesized that ctDNA, ddPCR, CA19-9, and CEA dynamics would be associated with treatment response. Methods: In this prospective, single-center study, patients with metastatic PDAC were monitored using blood-based biomarkers with high temporal resolution. Signatera (a ctDNA reporter panel informed by whole-exome sequencing) and digital droplet PCR (ddPCR of KRAS codon 12/13 mutations) were used along with standard CA19-9 and CEA. Blood markers were drawn at baseline and after 2, 4, and 8 weeks of treatment. Treatment response was measured by the RECIST 1.1 criteria or clinical deterioration. The primary objective was to evaluate the association of progression-free survival (PFS) with biomarker changes from baseline to 2 or 4 weeks. Results: Nineteen patients were enrolled, comprising 11 starting first-line (1L) therapy and 8 starting 2L. Sufficient tissue was available for tumor-informed ctDNA profiling in 12 of 19 patients (63%). ddPCR data were evaluated in 14 of the 19 patients and CA19-9 & CEA were evaluated in 19 of 19 patients. Overall median PFS was 3.5 months (1.9 - 4.3 months). A ctDNA reduction of at least 20% compared to baseline by week 2 and week 4 of treatment was associated with longer PFS (p=0.002 and p<0.001, respectively). Fluctuations in ddPCR by week 2 and week 4 compared to baseline were not associated with longer PFS at any threshold (all p-values>0.10 and p-values>0.19, respectively). Fluctuations in CA19-9 by week 2 of treatment were not associated with longer PFS at any threshold (all p-values>0.05); however, an increase of CA19-9 greater than 50% by week 4 of treatment was associated with worse PFS (p=0.002). Fluctuations in CEA by week 2 of treatment and week 4 of treatment were not associated with longer PFS at any threshold (all p-values>0.05). Among patients without a ctDNA increase at week 2, those who demonstrated a >80% reduction in ddPCR had significantly longer PFS (p<0.0001). Conclusions: Early reduction in ctDNA levels as early as 2-weeks and CA19-9 increases by week 4 of treatment were associated with worse PFS. These findings suggest utility of blood-based biomarkers for early treatment monitoring and could inform a prospective interventional trial evaluating ctDNA dynamics to inform early treatment decisions. Citation Format: James Lee, Amber Habowski, Baho Sidiqi, Adrianna Kapusta, Jenna Battaglia, Daniel King, James Lee. Tumor-informed ctDNA, ddPCR, CA19-9, and CEA to evaluate early treatment dynamics in patients with metastatic pancreatic cancer [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Advances in Pancreatic Cancer Research—Emerging Science Driving Transformative Solutions; Boston, MA; 2025 Sep 28-Oct 1; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2025;85(18_Suppl_3): nr A126.