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16.03.2016 | Original Article | Ausgabe 4/2016 Open Access

Cancer Chemotherapy and Pharmacology 4/2016

A phase I pharmacokinetics study comparing PF-06439535 (a potential biosimilar) with bevacizumab in healthy male volunteers

Zeitschrift:
Cancer Chemotherapy and Pharmacology > Ausgabe 4/2016
Autoren:
Beverly Knight, Danielle Rassam, Shanmei Liao, Reginald Ewesuedo
Wichtige Hinweise

Electronic supplementary material

The online version of this article (doi:10.​1007/​s00280-016-3001-2) contains supplementary material, which is available to authorized users.

Abstract

Purpose

This study compared the pharmacokinetics of PF-06439535, a potential bevacizumab biosimilar, to bevacizumab sourced from the European Union (bevacizumab-EU) and USA (bevacizumab-US), and of bevacizumab-EU to bevacizumab-US.

Methods

In this double-blind study, 102 healthy males, aged 21–55 years, were randomized 1:1:1 to receive a single 5 mg/kg intravenous dose of PF-06439535, bevacizumab-EU, or bevacizumab-US. Pharmacokinetic assessments were conducted for 71 days, with additional safety and immunogenicity assessments until day 100. Pharmacokinetic similarity was achieved if 90 % confidence intervals (CIs) for the test-to-reference ratios of the maximum serum concentration (Cmax), area under the serum concentration–time curve from zero to infinity (AUC0–∞), and from zero to time of last quantifiable concentration (AUC0–t) were within the 80.00–125.00 % bioequivalence acceptance window.

Results

The three study drugs exhibited similar pharmacokinetic properties. For the comparisons of PF-06439535 to bevacizumab-EU or bevacizumab-US, and of bevacizumab-EU to bevacizumab-US, the 90 % CIs for the ratios of Cmax, AUC0–t, and AUC0–∞ were all within 80.00–125.00 %. Two, one, and two subjects treated with PF-06439535, bevacizumab-EU, and bevacizumab-US, respectively, tested positive for antidrug antibodies, none of whom tested positive for neutralizing antibodies. Treatment-related adverse events were reported in 15.2, 25.7, and 18.2 % of subjects in the PF-06439535, bevacizumab-EU, and bevacizumab-US treatment arms, respectively.

Conclusions

This study demonstrated the pharmacokinetic similarity of PF-06439535 to both bevacizumab-EU and bevacizumab-US, and of bevacizumab-EU to bevacizumab-US. The safety profile (including immunogenicity) was similar in the three treatment groups, with no significant safety findings reported.

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Zusatzmaterial
Fig. S1 Study design. a Hours at which samples were collected for ADA. Samples for PK were collected at all times shown. ADA antidrug antibody; AE adverse event, PK pharmacokinetics. (EPS 1968 kb)
280_2016_3001_MOESM1_ESM.eps
Fig. S2 Individual and geometric mean C max, AUC0-t , and AUC0-∞ for PF-06439535, bevacizumab-EU, and bevacizumab-US. (a) C max; (b) AUC0-t ; and (c) AUC0-∞ . Stars (★) represent geometric mean and circles (o) represent individual subject values. Box plot provides median and 25 %/75 % quartiles with whiskers to the last point within 1.5 × inter-quartile range. AUC 0-∞ area under the serum concentration-time profile from zero extrapolated to infinite time; AUC 0-t area under the serum concentration-time profile from zero to the time of the last quantifiable concentration; C max maximum observed serum concentration. (EPS 2415 kb)
280_2016_3001_MOESM2_ESM.eps
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