Prognostic value of serum tumor markers in phase I immunotherapy trials: A single-institution retrospective analysis.

e14534 Background: Serum tumor markers are routinely monitored in patients with advanced solid tumors, but their utility in the phase I immunotherapy setting is not well established. We investigated whether baseline and best overall response (BOR) levels of these markers, and their changes during treatment, correlate with response and survival outcomes in patients on phase I immunotherapy trials across multiple tumor types. Methods: We retrospectively analyzed patients enrolled on phase I immunotherapy trials at our center between April 2017 and May 2023, with paired tumor marker assessments at baseline (within 30 days cycle 1 day 1 [C1D1]) and at BOR (within 21 days of BOR date, during which time patients received only study treatment). Markers analyzed included CA15-3 (breast), CA125 (ovarian), CA19-9 (pancreatic, cholangiocarcinoma, gastric/gastroesophageal junction [GEJ]), and CEA (colorectal, pancreatic, gastric/GEJ). In pancreatic cancer, CA19-9 was the primary analysis and CEA was exploratory. Associations between marker levels and BOR were assessed using Fisher's exact and Kruskal-Wallis tests. Spearman correlation evaluated relationships between marker percent change and radiographic response. Univariate Cox regression assessed associations with overall survival (OS), time to progression (TTP), and progression-free survival (PFS). Results: 106 patients with paired baseline and BOR marker data were included: colorectal (n = 35), pancreatic (n = 30), breast (n = 15), ovarian (n = 15), cholangiocarcinoma (n = 6), and gastric/GEJ (n = 5). Median age was 59 years; 61.3% were female; 74.5% received combination immunotherapy. In pancreatic cancer, CA19-9 levels at BOR were significantly higher in patients with progressive disease (PD) compared to stable disease (SD) or partial response (PR) (median 9,500 vs 535.4 vs 173.5 U/mL; p = 0.026). CA19-9 percent change from baseline to BOR positively correlated with radiographic response change (ρ = 0.44, p = 0.02). On Cox regression, CA19-9 percent change was associated with worse OS (HR 1.02 per 10% increase, 95% CI 1.00-1.04; p = 0.014), TTP (HR 1.02, p = 0.029), and PFS (HR 1.02, p = 0.029). In colorectal cancer, elevated CEA at BOR ( > 3.8 ng/mL) was associated with worse OS (HR 4.65, 95% CI 1.10-19.71; p = 0.037). Greater radiographic tumor burden change was associated with worse OS (HR 1.23 per 10% increase, p = 0.038), TTP (HR 1.34, p = 0.003), and PFS (HR 1.33, p = 0.003). Conclusions: Changes in tumor marker levels—particularly CA19-9 in pancreatic cancer and CEA in colorectal cancer—provide prognostic information in phase I immunotherapy trials, though concordance with radiographic change was modest. Given the challenges of early response assessment with immunotherapy, tumor markers may serve as a practical adjunct to imaging for longitudinal monitoring. Prospective validation and longitudinal trajectory analysis are warranted.