Abstract
Objective: This study compared the pharmacokinetics (PK), safety, and immunogenicity of the biosimilar TAB008 monoclonal antibody to bevacizumab (Avastin®) in normal healthy Chinese male volunteers. Methods: In this randomized, double-blind, parallel controlled study, a total of 100 healthy Chinese male subjects were randomized (1:1) to receive a single 1 mg/kg intravenous dose of TAB008 or Avastin® over a 90-min infusion. The subjects were followed for 99 days after drug administration. Primary endpoints were bioequivalence of major pharmacokinetic parameters (AUC0-t and AUC0-∞) and maximum observed serum concentration (Cmax). Secondary endpoints included safety and immunogenicity parameters. Results: The two groups of test subjects (49 subjects in the TAB008 group and 50 subjects in the Avastin® group) were well matched in regards to all demographic and baseline characteristics. The treatment group ratios of LS geometric means for the three primary PK parameters were fully contained within the bioequivalence limits of 80.00–125.00% (90% CI was 103.66–118.33% for Cmax, 94.32–111.72% for AUC0-t, and 94.69–112.23% for AUC0-∞). Treatment-emergent adverse events (TEAEs) were reported for 24 (49.0%) subjects in the TAB008 group and 22 (44.0%) subjects in the Avastin® group. TEAEs related to the study drug were reported for 19 (38.8%) subjects in the TAB008 group and 19 (38.0%) subjects in the Avastin® group. National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) Grade 3 TEAEs were reported for 1 (2.0%) subject in the TAB008 group and 3 (6.0%) subjects in the Avastin® group. There were no Grade 4 or 5 TEAEs or serious adverse events (SAEs) during the study. Anti-drug antibody generation was reported once only in each group, and neutralizing antibody (Nab) analysis was negative upon follow-up. Conclusion: TAB008 attained pharmacokinetic similarity to bevacizumab, and was safe and well tolerated.
Highlights
Bevacizumab (Avastin®) is a recombinant humanized monoclonal IgG1 antibody that effectively binds to and inhibits vascular endothelial growth factor (VEGF), thereby reducing new blood vessel formation
Treatment-emergent adverse events (TEAEs) related to the study drug were reported for 19 (38.8%) subjects in the TAB008 group and 19 (38.0%) subjects in the Avastin® group: withdrawal of consent (Avastin)® group
The mean concentration profiles between TAB008 Monoclonal Antibody Injection and Avastin® were similar over the profiling interval
Summary
Bevacizumab (Avastin®) is a recombinant humanized monoclonal IgG1 antibody that effectively binds to and inhibits vascular endothelial growth factor (VEGF), thereby reducing new blood vessel formation Avastin® was first approved by the United States Food and Drug Administration (FDA) in February 2004 for firstline treatment of metastatic colorectal cancer in combination with chemotherapy, and for first-line treatment of advanced non-squamous non-small cell, non-EGFR-mutant lung cancer (NSCLC) in combination with paclitaxel and carboplatin. In 2014, significant efficacy was demonstrated against cervical and ovarian cancer. All these approvals were based on stringent randomized clinical trials with significant overall survival improvement as the cornerstone for approval. In the European Union, aside from the previously mentioned indications, the EMA approved Avastin® in combination with EGFR tyrosine kinase inhibitors as first-line therapy in EGFR-mutant NSCLCs, and first-line treatment in combination with paclitaxel or capecitabine (if paclitaxel-intolerant) for triple-negative breast cancer.
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