Abstract 6447: Development of a fully automated immunoassay system of serum pembrolizumab to forecast therapeutic effectiveness
Authors: Noda Naotaka , Takahashi Takuya , Yagishita Shigehiro , Miura Masahiro , Takahashi Yusuke , Irino Yasuhiro , Yanagida Masatoshi , Hamada Akinobu 
Published: March 2024

Abstract
Recently, immuno-oncology treatments utilizing immune checkpoint inhibitors including pembrolizumab have attracted attention. Such treatments demonstrate potential effectiveness against cancers resistant to existing drugs, while offering the benefit of reduced side effects. Nonetheless, there is a specific group of patients who do not experience adequate therapeutic benefits from pembrolizumab. Despite the issue, the development of a comprehensive evaluation system to forecast therapeutic effectiveness is still in development. A strategy to predict therapeutic effectiveness involves evaluating the trough level or the steady state plasma-concentration of a drug in the blood. Ohuchi, M. et al. (Lung Cancer, 2022) demonstrated that patients with lower trough levels have shorter overall survival and progression-free survival durations, according to LC-MS/MS measurement of pembrolizumab. Furthermore, Wang, N. et al (Lung Cancer, 2023) demonstrated that the optimization of the dosage interval, grounded on the steady state plasma-concentration (target concentration, 15 µg/mL) of pembrolizumab, extended the duration of progression-free survival. Despite the potential of LC-MS/MS measurements in predicting patient prognosis and the benefits of PK-guided therapy, their implementation in clinical settings is hindered by the complex and time-consuming pre-treatment process for samples. Consequently, there is a growing need for a practical and clinically feasible drug concentration measurement system. Aiming to construct a clinically applicable pembrolizumab measurement system, we have been dedicated to developing a fully automated immunoassay system using anti-pembrolizumab antibodies. We developed two measurement systems of pembrolizumab in serum using two different antibodies targeting pembrolizumab. Using less than 10 µl serum, these systems can quantify the concentration of pembrolizumab ranging from 0.125 to 500 µg/mL within an hour, thereby enabling PK-guided therapy in clinical settings. After developing the measurement systems, we performed a correlation analysis with the LC-MS/MS system, using 70 samples with varying pembrolizumab concentrations ranging from 1.80 to 85.0 µg/mL. The results demonstrated that our measurement systems have a good correlation with LC-MS/MS measurement. Furthermore, the two immunometric measurement systems demonstrated a significant correlation with each other, substantiating the accuracy of the newly developed measurement system in determining the levels of pembrolizumab in the serum. The fully automated immunoassay systems we developed can measure pembrolizumab in serum within an hour, potentially paving the way for personalized treatment based on the serum concentration of pembrolizumab in clinical practice.
Citation Format: Naotaka Noda, Takuya Takahashi, Shigehiro Yagishita, Masahiro Miura, Yusuke Takahashi, Yasuhiro Irino, Masatoshi Yanagida, Akinobu Hamada. Development of a fully automated immunoassay system of serum pembrolizumab to forecast therapeutic effectiveness [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6447.