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Population pharmacokinetic and pharmacodynamic analysis of tremelimumab in patients with metastatic melanoma
Author(s) -
Wang Erjian,
Kang Dongwoo,
Bae KyunSeop,
Marshall Margaret A.,
Pavlov Dmitri,
Parivar Kourosh
Publication year - 2014
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1002/jcph.309
Subject(s) - tremelimumab , pharmacodynamics , pharmacokinetics , medicine , population pharmacokinetics , metastatic melanoma , oncology , melanoma , pharmacology , population , ipilimumab , immunotherapy , cancer research , cancer , environmental health
Tremelimumab, a fully human monoclonal antibody specific for human cytotoxic T‐lymphocyte‐associated antigen 4, has been studied in clinical trials. We have reported the results of population pharmacokinetics for tremelimumab in 654 metastatic melanoma patients. Population estimates (inter‐individual variability [IIV]) for pharmacokinetic parameters in a final model were clearance (CL), 0.26 L/day (31.8%) and central volume of distribution, 3.97 L (20.4%). CL was faster in males, patients with higher values of creatinine clearance and endogenous immunoglobulin, and patients with relatively poor baseline prognostic factors. No dose adjustment was needed based on the magnitude of the change of CL (<30%). The association of CL and overall survival (OS) was investigated. In a Phase 3 trial evaluating tremelimumab as first‐line‐treatment, median OS for the 147 patients in the fast‐CL group (≥median CL value) was 9.6 months versus 15.8 months for the 146 patients in the slow‐CL group (