Evaluation of the exposure-response relationship of pembrolizumab in non-small cell lung cancer: observational study protocol in real-world clinical practice

Pembrolizumab is a monoclonal antibody used in various oncological indications. This antibody is directed against programmed cell death receptor type 1. The expression of this receptor is used as a marker of treatment efficacy. In the search for response biomarkers, several authors have studied the relationship between plasma concentrations of pembrolizumab and response to treatment. However, these results are contradictory, and greater knowledge of the exposure-response association of these drugs is needed to predict response based on blood concentrations. The two primary objectives are to study the relationship between the pembrolizumab minimum steady-state concentration and (1) progression-free survival and (2) the clinical benefit rate, in patients with metastatic non-small cell lung cancer. We designed a prospective, longitudinal, observational study at a single center. Patients with metastatic non-small cell lung cancer undergoing treatment with pembrolizumab are being included. Peripheral blood samples will be collected from enrolled patients at treatment initiation and, once steady state is reached, at each treatment reassessment, coinciding with routine blood tests. Once plasma is obtained from the samples, it will be frozen until analysis. The plasma drug concentration will be measured using specific commercial ELISA test kits. Demographic, clinical, and treatment data will be collected in a data collection form. With this project, we want to advance personalized cancer medicine by providing real-world data. Because resources are limited, establishing guidelines that reduce costs while maintaining the same efficacy would allow us to be more efficient. The limitations of this project stem from its single-center nature, which limits the number of patients and blood samples. This project is registered in the Spanish Clinical Studies Registry of the Spanish Agency of Medicines and Medical Devices under the title: “NIPE-TDM Study: Evaluation of the concentration–response relationship of immunotherapy in oncology patients: real-world clinical experience,” code: NIPE-TDM, identifier: 0131-2024-OBS, AEMPS No.: 24-00145.