title: Evaluation of Immunogenicity of Nivolumab Monotherapy and Its Clinical Relevance in Patients With Metastatic Solid Tumors.
abstract: Nivolumab is a fully human IgG4 monoclonal antibody targeting the programmed death-1 (PD-1) receptor that blocks interactions between PD-1 and its ligands on tumor cells to prevent T-cell exhaustion in patients with cancer. It has demonstrated efficacy in multiple tumor types, including melanoma, non-small-cell lung cancer, and renal cell carcinoma. This analysis assessed the immunogenicity of nivolumab and its impact on pharmacokinetics, safety, and efficacy in patients with solid tumors enrolled in 6 clinical studies. The incidence and prevalence of antidrug antibodies (ADAs) were determined by validated electrochemiluminescence assays in samples collected during nivolumab treatment and up to 100 days after the last dose. Confirmed positive samples from the 6 studies were also tested for presence of neutralizing antibodies (NAbs). Among 1086 nivolumab-treated patients, 138 patients (12.7%) were ADA positive (relative to baseline), only 3 (0.3%) of whom were persistently positive for ADA, and 9 (0.8%) were NAb positive at 1 time point. The presence of ADAs was not associated with hypersensitivity, infusion reactions, or loss of efficacy and had minimal impact on nivolumab clearance. Additionally, the presence of NAbs was not associated with loss of efficacy. In conclusion, immunogenicity of nivolumab is not clinically meaningful.
authors.affiliation: Clinical Pharmacology and Pharmacometrics, Bristol-Myers Squibb, Princeton, NJ, USA.
authors.forename: Shruti
authors.initials: S
authors.lastname: Agrawal
authors.affiliation: Clinical Pharmacology and Pharmacometrics, Bristol-Myers Squibb, Princeton, NJ, USA.
authors.forename: Paul
authors.initials: P
authors.lastname: Statkevich
authors.affiliation: Clinical Pharmacology and Pharmacometrics, Bristol-Myers Squibb, Princeton, NJ, USA.
authors.forename: Gaurav
authors.initials: G
authors.lastname: Bajaj
authors.affiliation: Clinical Pharmacology and Pharmacometrics, Bristol-Myers Squibb, Princeton, NJ, USA.
authors.forename: Yan
authors.initials: Y
authors.lastname: Feng
authors.affiliation: Bioanalytical Sciences, Biologics, Bristol-Myers Squibb, Princeton, NJ, USA.
authors.forename: Sally
authors.initials: S
authors.lastname: Saeger
authors.affiliation: Bioanalytical Sciences, Biologics, Bristol-Myers Squibb, Princeton, NJ, USA.
authors.forename: Dharmesh D
authors.initials: DD
authors.lastname: Desai
authors.affiliation: Global Biometric Sciences, Bristol-Myers Squibb, Princeton, NJ, USA.
authors.forename: Jong-Soon
authors.initials: JS
authors.lastname: Park
authors.affiliation: Global Clinical Research, Bristol-Myers Squibb, Princeton, NJ, USA.
authors.forename: Ian M
authors.initials: IM
authors.lastname: Waxman
authors.affiliation: Clinical Pharmacology and Pharmacometrics, Bristol-Myers Squibb, Princeton, NJ, USA.
authors.forename: Amit
authors.initials: A
authors.lastname: Roy
authors.affiliation: Clinical Pharmacology and Pharmacometrics, Bristol-Myers Squibb, Princeton, NJ, USA.
authors.forename: Manish
authors.initials: M
authors.lastname: Gupta
mesh_terms: D000906:Antibodies / Q000276:immunology; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000276:immunology* / Q000493:pharmacokinetics / Q000627:therapeutic use*; D057134:Antibodies, Neutralizing / Q000276:immunology; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000276:immunology* / Q000493:pharmacokinetics / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy*; D000077594:Nivolumab
chemical_list: D000906:Antibodies; D000911:Antibodies, Monoclonal; D057134:Antibodies, Neutralizing; D000970:Antineoplastic Agents; D000077594:Nivolumab
keywords: antidrug antibodies; immunogenicity; immunotherapy; nivolumab; pharmacokinetics; programmed death-1