title: Development and validation of an ELISA method for the quantification of nivolumab in plasma from non-small-cell lung cancer patients.
abstract: Nivolumab, an anti PD-1 monoclonal antibody, has been approved for the treatment of previously treated advanced or metastatic non-small-cell lung cancer (NSCLC). The aim of this study was to develop and validate an ELISA method for the quantification of nivolumab in plasma from patients with NSCLC in order to perform future pharmacokinetic/pharmacodynamic (PK/PD) studies. A home-made ELISA was developed and validated according to the general recommendations for the immunoassays. Then, the ELISA method was applied to quantify plasma trough levels (Cmin) of nivolumab (3mg/kg every two weeks) in 27 NSCLC patients at days 14, 28 and 42 after start of treatment. Blood samples were collected just before the infusion on days 0 (baseline), 14, 28 and 42 after start of treatment. The dynamic calibration range for nivolumab assay was 5-100μg/mL. Within- and between-day imprecision for quality controls (5, 20 and 75μg/mL) were less than 5 and 12%, respectively. The mean (±standard deviation) nivolumab Cminwas 17.3±4.8μg/mL (coefficient of variation, CV=27.8%), 25.0±9.7μg/mL (CV=38.8%) and 33.0±12.9μg/mL (CV=39.1%) on days 14, 28 and 42, respectively. IgG (p=0.002) and ALT (p=0.041) were independently associated with plasma nivolumab Cminat day 42. The present ELISA method for quantification of nivolumab in plasma from NSCLC patients is sensitive and accurate enough to be used for further PK/PD investigations.
authors.affiliation: Department of Pharmacokinetics and Pharmacochemistry, Hôpital Cochin, AP-HP, Paris, France.
authors.forename: Alicja
authors.initials: A
authors.lastname: Puszkiel
authors.affiliation: Department of Pharmacokinetics and Pharmacochemistry, Hôpital Cochin, AP-HP, Paris, France; UMR8638 CNRS, Faculté de Pharmacie de Paris, Université Paris Descartes, PRES Sorbonne Paris Cité, Paris, France.
authors.forename: Gaëlle
authors.initials: G
authors.lastname: Noé
authors.affiliation: Department of Medical Oncology, Hôpital Cochin, AP-HP, Paris, France; Université Paris Descartes, CARPEM, Paris, France; Immunomodulatory Therapies Multidisciplinary Study group (CERTIM), Hôpital Cochin, AP-HP, Paris, France.
authors.forename: Pascaline
authors.initials: P
authors.lastname: Boudou-Rouquette
authors.affiliation: Directorate of medical organization, AP-HP, France.
authors.forename: Chloé Le-
authors.initials: CL
authors.lastname: Cossec
authors.affiliation: Department of Medical Oncology, Hôpital Cochin, AP-HP, Paris, France; Université Paris Descartes, CARPEM, Paris, France; Immunomodulatory Therapies Multidisciplinary Study group (CERTIM), Hôpital Cochin, AP-HP, Paris, France.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Arrondeau
authors.affiliation: Department of Pharmacokinetics and Pharmacochemistry, Hôpital Cochin, AP-HP, Paris, France.
authors.forename: Jean-Stephane
authors.initials: JS
authors.lastname: Giraud
authors.affiliation: Department of Pharmacokinetics and Pharmacochemistry, Hôpital Cochin, AP-HP, Paris, France; UMR8638 CNRS, Faculté de Pharmacie de Paris, Université Paris Descartes, PRES Sorbonne Paris Cité, Paris, France; Immunomodulatory Therapies Multidisciplinary Study group (CERTIM), Hôpital Cochin, AP-HP, Paris, France.
authors.forename: Audrey
authors.initials: A
authors.lastname: Thomas-Schoemann
authors.affiliation: Department of Medical Oncology, Hôpital Cochin, AP-HP, Paris, France; Université Paris Descartes, CARPEM, Paris, France; Immunomodulatory Therapies Multidisciplinary Study group (CERTIM), Hôpital Cochin, AP-HP, Paris, France; U1016 INSERM, UMR 8104 CNRS, UMR-S1016, Université Paris Descartes, Sorbonne Paris Cité, Paris, France; Groupe de Pharmacologie Clinique Oncologique (GPCO), Paris, France.
authors.forename: Jérôme
authors.initials: J
authors.lastname: Alexandre
authors.affiliation: Department of Pharmacokinetics and Pharmacochemistry, Hôpital Cochin, AP-HP, Paris, France; UMR8638 CNRS, Faculté de Pharmacie de Paris, Université Paris Descartes, PRES Sorbonne Paris Cité, Paris, France; Immunomodulatory Therapies Multidisciplinary Study group (CERTIM), Hôpital Cochin, AP-HP, Paris, France.
authors.forename: Michel
authors.initials: M
authors.lastname: Vidal
authors.affiliation: Department of Medical Oncology, Hôpital Cochin, AP-HP, Paris, France; Université Paris Descartes, CARPEM, Paris, France; Immunomodulatory Therapies Multidisciplinary Study group (CERTIM), Hôpital Cochin, AP-HP, Paris, France; U1016 INSERM, UMR 8104 CNRS, UMR-S1016, Université Paris Descartes, Sorbonne Paris Cité, Paris, France.
authors.forename: François
authors.initials: F
authors.lastname: Goldwasser
authors.affiliation: Department of Pharmacokinetics and Pharmacochemistry, Hôpital Cochin, AP-HP, Paris, France; Immunomodulatory Therapies Multidisciplinary Study group (CERTIM), Hôpital Cochin, AP-HP, Paris, France; Groupe de Pharmacologie Clinique Oncologique (GPCO), Paris, France. Electronic address: benoit.blanchet@aphp.fr.
authors.forename: Benoit
authors.initials: B
authors.lastname: Blanchet
mesh_terms: D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000097:blood*; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000097:blood*; D002289:Carcinoma, Non-Small-Cell Lung / Q000097:blood* / Q000188:drug therapy; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods / Q000592:standards; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D008175:Lung Neoplasms / Q000097:blood* / Q000188:drug therapy; D008297:Male; D008875:Middle Aged; D000077594:Nivolumab
chemical_list: D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D000077594:Nivolumab
keywords: Anti PD-1 monoclonal antibody; Immunoassay; Nivolumab; Non-small-cell lung cancer; Pharmacokinetics