Quantitative Characterization of the Exposure-Response Relationship for Cancer Immunotherapy: A Case Study of...

To inform the benefit-risk assessment of nivolumab in patients with advanced melanoma, analyses of efficacy and safety exposure-response (E-R) relationships were conducted with data from patients with advanced melanoma enrolled in two clinical studies (phase I and phase III) who received nivolumab 0.1-10.0 mg/kg every 2 weeks. E-R efficacy analyses were performed by relating the nivolumab time-averaged concentration after the first dose (C_avg1 ) to two endpoints: RECIST objective response (OR) and overall survival (OS). E-R safety analyses characterized the relationship between nivolumab C_avg1 and the hazard of all-causality adverse events leading to discontinuation or death (AE-DC/D). Nivolumab exposure represented by C_avg1 was not a significant predictor of OR, OS, or the hazard of AE-DC/D. E-R efficacy and safety relationships were relatively flat over the exposure range.