Abstract 7753: Circulating thymidine kinase activity (TKa) as a predictive and dynamic biomarker in the metastatic non-small cell lung cancer (NSCLC): Immunoblood study

Abstract Introduction: Despite major advances with immune checkpoint inhibitors (ICIs) in treatment of metastatic NSCLC, reliable biomarkers to predict who will benefit from therapy and monitor early treatment response remain limited. Thymidine kinase is an enzyme fundamental in the DNA synthesis, its activity reflects tumor cell proliferation and tumor aggressiveness. This study (NCT06823401) is the first to evaluate plasma TKa levels in NSCLC patients receiving immunotherapy (IT) or chemotherapy-IT (CHT-IT). The objectives were to determine whether baseline TKa levels can predict efficacy of IT and if early on-treatment changes in TKa levels reflect treatment response, thereby supporting TKa as a minimally invasive biomarker for patient therapy selection and early efficacy assessment. The capacity of TKa to evaluate cell proliferation is expected to reflect and predict successful T-cell activation of IT and prolonged efficacy. Methods: 94 patients (50 males, 44 females) with metastatic NSCLC, had plasma samples collected at baseline (pre-treatment) and at second treatment cycle of whom 93 received first-line systemic therapy. Circulating TKa was measured using the FDA cleared and CE marked DiviTum® TKa assay (Biovica, Sweden), with values reported in DiviTum units of activity (DuA). Analysis was performed blinded to clinical outcomes. TKa was evaluated for its association with response rate (RR), progression-free survival (PFS), overall survival (OS) and was also correlated to other biomarkers, including PD-L1 expression. Results: 65 pts (70%) received first-line CHT-IT, while 28 pts (30%) received IT alone. PD-L1 expression was <1% in 37 pts (40%), 1-49% in 17 pts (18%), ≥50% in 34 pts (36%), and unknown in 6 pts (6%). The median baseline TKa level was 203 DuA. The RR in the low (<203 DuA) and high-TKa group was 52% and 32% respectively (p = 0.80) while the mPFS was not reached in the low TKa group versus 7.3 mos in high TKa group (p = 0.13). The 1-year OS rate was similar between the two groups (69.9% vs 62.4%, p = 0.34). Using a TKa cutoff of 326 DuA, we observed a statistically significant difference in mPFS; 13.8 months in the low-TKa group (65 pts) versus 3.3 months in the high-TKa group (23 pts) (p = 0.004). The 1-year OS rate was 65.6% vs 53.3%, respectively (p = 0.18). Further data on patients treated with IT alone and with CHT-IT will be presented at the meeting. Conclusions: Our study shows a possible association between high plasma TKa levels and shorter PFS and OS in advanced NSCLC treated with first-line IT alone or combined with CHT, supporting the potential role in guiding treatment choice. Further studies are needed to validate the prognostic and predictive value of TKa in this setting. Citation Format: Maristella Giammaruco, Lorenza Landi, Mattias Bergqvist, Gabriele Minuti, Silvia Carpano, Francesca Fusco, Martina Brandi, Fabiana Letizia Cecere, Vincenzo Pio Di Noia, Livia Tosetto, Andrea Torchia, Corrado Orciuolo, Daniele Marinelli, Grisel Maver Militello, Diana Giannarelli, Federico Cappuzzo. Circulating thymidine kinase activity (TKa) as a predictive and dynamic biomarker in the metastatic non-small cell lung cancer (NSCLC): Immunoblood study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 7753.