Association of Time‐Varying Clearance of Nivolumab With Disease Dynamics and Its Implications on Exposure Response Analysis
Citations Over TimeTop 1% of 2017 papers
Abstract
Nivolumab is a human monoclonal antibody that blocks the interaction between PD-1 programmed death-1 (PD-1) and its ligands, PD-L1 and PD-L2. Nivolumab demonstrated efficacy in clinical trials for various types of cancer. A time-varying clearance was identified for nivolumab. We show that the change of clearance over time is associated with the post-treatment effects: clearance decreases when disease status improves. This interaction between posttreatment effects and drug exposure may lead to a biased steep estimate of the exposure-response (E-R) relationship for efficacy. Under this scenario, simulations were performed to develop a proposed methodology to assess the causal effect of drug exposure upon clinical response. Data from nivolumab trials were subsequently used to verify the proposed methodology for E-R analysis. The results showed that E-R analysis results based on pharmacokinetic (PK) metrics derived from the first dose are more consistent with the true E-R or dose-response relationship than the steady-state PK metrics.
Related Papers
- → Tumor Mutational Burden and Efficacy of Nivolumab Monotherapy and in Combination with Ipilimumab in Small-Cell Lung Cancer(2018)886 cited
- → Severe infusion reaction due to nivolumab: A case report(2020)8 cited
- → A Pooled Analysis of 3 Phase II Trials of Salvage Nivolumab/Ipilimumab After Nivolumab in Renal Cell Carcinoma(2023)3 cited
- BIOLUMA: Biomarkers for nivolumab and evaluation of nivolumab plus ipilimumab in lung cancer(2018)
- → P2.04-39 Clinical Characteristics of Long-Term Survivors with Nivolumab in Previously Treated Advanced NSCLC from Real World Data(2019)