A phase 1 randomized study compare the pharmacokinetics, safety and immunogenicity of HLX04 to reference bevacizumab sourced from the United States, the European Union, and China in healthy Chinese male volunteers.
Cancer Chemother Pharmacol
; 88(3): 465-474, 2021 09.
Article
em En
| MEDLINE
| ID: mdl-34086067
ABSTRACT
PURPOSE:
To compare the pharmacokinetic profiles, safety and immunogenicity of proposed bevacizumab biosimilar HLX04 with reference bevacizumab in healthy Chinese males.METHODS:
In this double-blind Phase 1 study, healthy volunteers (N = 208) were randomized 1111 to a single 3 mg/kg intravenous infusion of HLX04 or reference bevacizumab sourced from the United States (bevacizumab-US), the European Union (bevacizumab-EU) or China (bevacizumab-CN). Co-primary endpoints were area under the serum concentration-time profile (AUC) from time zero extrapolated to infinity (AUC0-inf) and from zero to last quantifiable concentration (AUClast). Secondary endpoint was the maximum serum drug concentration (Cmax). Study participants were monitored for treatment-emergent adverse events (TEAEs) and samples were collected for anti-drug antibody (ADA) testing throughout the study.RESULTS:
Pharmacokinetic parameters were similar across groups. The respective geometric least-squares mean ratios (GLSMR) of AUC0-inf, AUClast and Cmax were 95.7%, 96.0% and 101.8% for HLX04 versus bevacizumab-US; 94.3%, 94.6% and 100.5% for HLX04 versus bevacizumab-EU; and 90.0%, 90.4% and 98.2% for HLX04 versus bevacizumab-CN. For all test-to-reference comparisons, two-sided 90% confidence intervals of GLSMR for AUC0-inf, AUClast and Cmax fell in the pre-specified bioequivalence range (80-125%). There were no notable differences in the frequency, nature and/or grade of TEAEs. No deaths were reported and no ADAs were detected during the study.CONCLUSION:
HLX04 had similar safety and pharmacokinetic profiles to reference bevacizumab in healthy Chinese males, supporting the confirmatory Phase 3 study investigating the efficacy and safety equivalence between HLX04 and bevacizumab in patients with metastatic colorectal cancer (NCT03511963). CLINICAL TRIAL REGISTRATION The study was registered with Clinicaltrials.gov, NCT03483649.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Temas:
Geral
Base de dados:
MEDLINE
Assunto principal:
Povo Asiático
/
Medicamentos Biossimilares
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Bevacizumab
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Antineoplásicos Imunológicos
Tipo de estudo:
Clinical_trials
/
Prognostic_studies
Limite:
Adult
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Humans
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Male
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Middle aged
País/Região como assunto:
America do norte
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Asia
Idioma:
En
Revista:
Cancer Chemother Pharmacol
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
China