title: Quantitative Characterization of the Exposure-Response Relationship for Cancer Immunotherapy: A Case Study of Nivolumab in Patients With Advanced Melanoma.
abstract: 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 (Cavg1) to two endpoints: RECIST objective response (OR) and overall survival (OS). E-R safety analyses characterized the relationship between nivolumab Cavg1and the hazard of all-causality adverse events leading to discontinuation or death (AE-DC/D). Nivolumab exposure represented by Cavg1was 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.
authors.affiliation: Clinical Pharmacology and Pharmacometrics, Bristol-Myers Squibb, Princeton, New Jersey, USA.
authors.forename: X
authors.initials: X
authors.lastname: Wang
authors.affiliation: Clinical Pharmacology and Pharmacometrics, Bristol-Myers Squibb, Princeton, New Jersey, USA.
authors.forename: Y
authors.initials: Y
authors.lastname: Feng
authors.affiliation: Clinical Pharmacology and Pharmacometrics, Bristol-Myers Squibb, Princeton, New Jersey, USA.
authors.forename: G
authors.initials: G
authors.lastname: Bajaj
authors.affiliation: Clinical Pharmacology and Pharmacometrics, Bristol-Myers Squibb, Princeton, New Jersey, USA.
authors.forename: M
authors.initials: M
authors.lastname: Gupta
authors.affiliation: Clinical Pharmacology and Pharmacometrics, Bristol-Myers Squibb, Princeton, New Jersey, USA.
authors.forename: S
authors.initials: S
authors.lastname: Agrawal
authors.affiliation: Oncology Global Clinical Research, Bristol-Myers Squibb, Princeton, New Jersey, USA.
authors.forename: A
authors.initials: A
authors.lastname: Yang
authors.affiliation: Global Biometric Sciences, Bristol-Myers Squibb, Princeton, New Jersey, USA.
authors.forename: J-S
authors.initials: JS
authors.lastname: Park
authors.affiliation: Oncology Global Clinical Research, Bristol-Myers Squibb, Princeton, New Jersey, USA.
authors.forename: B
authors.initials: B
authors.lastname: Lestini
authors.affiliation: Clinical Pharmacology and Pharmacometrics, Bristol-Myers Squibb, Princeton, New Jersey, USA.
authors.forename: A
authors.initials: A
authors.lastname: Roy
mesh_terms: D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D017321:Clinical Trials, Phase I as Topic / Q000706:statistics & numerical data; D017326:Clinical Trials, Phase III as Topic / Q000706:statistics & numerical data; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007167:Immunotherapy / Q000379:methods* / Q000639:trends; D038622:Internationality; D008297:Male; D008545:Melanoma / Q000175:diagnosis / Q000188:drug therapy*; D008875:Middle Aged; D000077594:Nivolumab; D012878:Skin Neoplasms / Q000175:diagnosis / Q000188:drug therapy*; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D000077594:Nivolumab