A Phase I Clinical Study Comparing the Pharmacokinetics, Safety, and Immunogenicity of GB221 Injection and Trastuzumab (Herceptin(®)) in Healthy Chinese Adults.

GB221 is a recombinant humanized anti-HER2 monoclonal antibody. The purpose of this study was to evaluate the pharmacokinetic, safety, and immunogenicity of GB221 in healthy Chinese adults in comparison to trastuzumab (Herceptin®). In this randomized, double-blind, parallel-group phase I clinical trial, 88 subjects were randomized 1:1 to receive a single intravenous infusion (90-100 min) of GB221 or trastuzumab (6 mg/kg). The primary pharmacokinetic parameters-maximum observed serum concentration (Cmax), area under the serum concentration-time curve from zero to the last quantifiable concentration at time t (AUC0-t), and area under the serum concentration-time curve from time zero to infinity (AUC0-∞)-of GB221 and trastuzumab were compared to establish whether the 90% confidence interval (CI) attained the 80-125% bioequivalence standard. Safety and immunogenicity were also evaluated. The GB221 group (n = 43) and the trastuzumab group (n = 44) showed similar pharmacokinetic characteristics. The geometric mean ratios (90% CI) of Cmax, AUC0-t, and AUC0-∞ between the two groups were 107.53% (102.25-113.07%), 108.31% (103.57-113.26%), and 108.34% (103.57-113.33%), respectively. The incidence of treatment-emergent adverse events (TEAEs) was 83.7% (36/43) of the subjects in the GB221 group and 95.5% (42/44) of the subjects in the trastuzumab group. No subjects withdrew from the trial due to TEAEs, and there were no occurrences of serious adverse events. All subjects tested negative for antidrug antibodies (ADA). GB221 demonstrated similar pharmacokinetics to trastuzumab and comparable safety and immunogenicity in healthy Chinese adults.

Zhu Y ，Li C ，Chen L ，Liu H ，Ou L ，Li T ，Wang X ，Wang T ，Tian J ，Liang X ，Hu Z ，Zhan Y ，Xiao S ，Wang X ，Li Y ，He J ，Zheng Q ，Song H ，Li X ，Fang Y ... -  《-》

A randomized phase I clinical trial comparing the pharmacokinetic, safety, and immunogenicity of potential biosimilar recombinant human HER2 monoclonal antibody for injection and trastuzumab in healthy Chinese adults.

Wang J ，Niu S ，Dong W ，Wei L ，Ou L ，Zhang T ，Zhang L ，Nie X ，Wang Q ，Shen T ，Wang Q ，Xia L ，Liu G ，Jin J ，Zheng Q ，Song H ，Fang Y ... -  《-》

A randomized Phase I pharmacokinetic trial comparing the potential biosimilar trastuzumab (SIBP-01) with the reference product (Herceptin®) in healthy Chinese male volunteers.

Zhou H ，Cao S ，Zhu X ，Xie J ，Fan L ，Ge Q ，Wang Y ，Zhu J ，Liu Y ，Shao Z ，Shan R ，Liu B ，Wang H ，Ding L ... -  《-》

A randomized, double-blind, parallel pharmacokinetic study comparing the trastuzumab biosimilar candidate, AryoTrust®, and reference trastuzumab in healthy subjects.

Farmahini Farahani M ，Maghzi P ，Jafari Aryan N ，Payandemehr B ，Soni M ，Azhdarzadeh M ... -  《-》

A pharmacokinetics phase 1 bioequivalence study of the trastuzumab biosimilar MYL-1401O vs. EU-trastuzumab and US-trastuzumab.

Trastuzumab is a humanized monoclonal antibody that binds the human epidermal growth factor receptor 2 (HER2) oncoprotein and is an effective therapy for HER2-overexpressing breast cancer. MYL-1401O is a trastuzumab biosimilar. Here, we report results from a phase 1 study that investigated bioequivalence among MYL-1401O, reference EU-trastuzumab and US-trastuzumab. This single-centre, randomized, double-blind, three-arm, parallel-group, phase 1 study was conducted in healthy adult male volunteers. Subjects were randomized 1:1:1 to receive a single 8 mg kg-1 dose of MYL-1401O, EU-trastuzumab or US-trastuzumab as a 90-min intravenous infusion. The primary objective was to assess PK similarity among all three products. Primary endpoints assessed were peak serum concentration (Cmax), area under the serum concentration-time curve from time of dosing to time of last quantifiable concentration and from time of dosing to infinity. Secondary endpoints included time of Cmax, elimination rate constant, half-life, safety and immunogenicity. Of 132 subjects enrolled (44/treatment), 120 (MYL-1401O, n = 42; EU-trastuzumab, n = 41; US-trastuzumab, n = 37) were included in the PK analysis. The 90% confidence intervals of the ratios of geometric means for the primary endpoints were bounded within the predefined bioequivalence criterion of 80-125%. Secondary endpoints time of Cmax, elimination rate constant and half-life were similar among groups. All treatment-emergent adverse events were mild or moderate, similar across groups and no serious adverse events were reported. No treatment-related antidrug antibodies were detected. MYL-1401O was well tolerated and demonstrated PK and safety profiles similar to EU-trastuzumab and US-trastuzumab in healthy volunteers (ClinicalTrials.gov, NCT02594761).

Waller CF ，Vutikullird A ，Lawrence TE ，Shaw A ，Liu MS ，Baczkowski M ，Sharma R ，Barve A ，Goyal P ，Donnelly C ，Sengupta N ，Pennella EJ ... -  《-》