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D. Rassam
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P2.01 - Poster Session/ Treatment of Advanced Diseases – NSCLC (ID 207)
- Event: WCLC 2015
- Type: Poster
- Track: Treatment of Advanced Diseases - NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 9/08/2015, 09:30 - 17:00, Exhibit Hall (Hall B+C)
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P2.01-079 - A Phase I Study Comparing PF-06439535 (A Potential Biosimilar) with Bevacizumab (ID 698)
09:30 - 09:30 | Author(s): D. Rassam
- Abstract
Background:
PF-06439535, a potential biosimilar to bevacizumab, is a humanized monoclonal IgG1 antibody that targets the vascular endothelial growth factor. This study (B7391001) compared the pharmacokinetics (PK) of PF-06439535 to bevacizumab sourced from the US (bevacizumab-US) and EU (bevacizumab–EU), and the PK of bevacizumab-EU to bevacizumab–US in healthy male volunteers.
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-US, or bevacizumab-EU. One subject discontinued before dosing. Assessments for PK were conducted for 71 days, with extended safety and immunogenicity assessments up to 100 days postdose. PK similarity was achieved if 90% confidence intervals (CIs) for the test-to-reference ratios of the maximum concentration (C~max~), the area under the concentration-time curve (AUC) from time 0 to the last quantifiable time point (AUC~T~), and AUC from time 0 extrapolated to infinity (AUC~0-∞~) were within 80.00%–125.00%.
Results:
Ninety-seven subjects were eligible and included in the PK analysis. The demographics of the PK eligible subjects were comparable among the 3 treatment groups. The 3 study drugs exhibited similar PK parameters (Table 1). 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 C~max~, AUC~T~, and AUC~0-∞~ were all within 80.00%–125.00% (Table 2). 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. Table 1: Mean (±SD) PK Parameter Estimates
[a]AUC~T~ was ≥80% of the corresponding AUC~0-∞~ in all 97 PK eligible subjects. Table 2: Comparisons of Pharmacokinetic Exposure Parameters between Test and Reference ProductsParameters (units) PF-06439535 Bevacizumab-EU Bevacizumab-US N 32 33 32 C~max~ (µg/mL) 142.9 ± 20.3 137.0 ± 20.5 130.0 ± 18.2 AUC~T~ (µg•hr/mL)[a] 40840 ± 6411 41010 ± 6711 38920 ± 4566 AUC~0-∞~ (µg•hr/mL) 43080 ± 7103 43830 ± 8326 41450 ± 5350
[a]Adjusted geometric meansComparison (Test to Reference) Parameters, units Test[a] Reference[a] Test/Reference Ratio (%) 90% CI for Ratio PF-06439535 to bevacizumab-EU C~max~, µg/mL 141.5 135.5 104.42 98.36–110.84 AUC~T~, µg•hr/mL 40330 40490 99.62 93.69–105.93 AUC~0-∞~, µg•hr/mL 42490 43100 98.58 92.16–105.44 PF-06439535 to bevacizumab-US C~max~, µg/mL 141.5 128.9 109.79 103.38–116.60 AUC~T~, µg•hr/mL 40330 38660 104.32 98.06–110.97 AUC~0-∞~, µg•hr/mL 42490 41120 103.33 96.55–110.58 Bevacizumab-EU to bevacizumab-US C~max~, µg/mL 135.5 128.9 105.15 99.05–111.62 AUC~T~, µg•hr/mL 40490 38660 104.71 98.48–111.34 AUC~0-∞~, µg•hr/mL 43100 41120 104.82 98.00–112.12
Conclusion:
This study demonstrates PK similarity of PF-06439535 to both bevacizumab-US and bevacizumab-EU, and of bevacizumab-EU to bevacizumab-US. The safety profile was similar in the 3 treatment groups with no significant safety findings reported.
