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

Zhou, Huan; Cao, Shugang; Zhu, Xingyu; Xie, Jing; Ge, Qi; Wang, Ying; Zhu, Jie; Liu, Yuanyuan; Shao, ZhongHuan; Shan, Rongfang; Liu, Bingyan; Wang, Hongju; Ding, Li

doi:10.1080/17425255.2020.1807935

Cited by 9 publications

(11 citation statements)

References 19 publications

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“…al found that elevation of direct bilirubin and upper respiratory tract infection were most common AEs after trastuzumab administration in their study, with an incidence of 53.3% and 33.3%, respectively (Swain et al, 2014). All reported AEs were mild or moderate, and no serious adverse reactions (Yin et al, 2014;Zhang et al, 2021;Zhou et al, 2020). QLHER2 and Herceptin were well tolerated in our study, and most types of drug-related AEs were reported in the literatures.…”

Section: Discussionsupporting

confidence: 61%

A Comparative Pharmacokinetic Study to Evaluate the Bioequivalence and Safety of A Humanized Recombinant Monoclonal Antibody Targeting Human Epidermal Growth Factor Receptor 2 (HER2) with the Reference Herceptin in Healthy Chinese Subjects

Ding

Huang

Feng

et al. 2022

Preprint

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Purpose:This study aimed to evaluate the safety, tolerability, pharmacokinetics and bioequivalence of a test humanized recombinant monoclonal antibody targeting Human Epidermal Growth Factor receptor 2 (HER-2) with the reference Herceptin®.Materials and methods:The trial consists of two parts (part I and part II). Part I was an open-label, sequential-cohort dose-escalation study, QLHER2 (test) was intravenous infusion at single doses escalating from 0.2 to 6 mg/kg (0.2, 1, 2, 4 and 6mg/kg) and Herceptin(reference) 4 mg/kg in 16 healthy subjects, to evaluated the safety, tolerability and pharmacokinetics of QLHER2. Part II was a randomized, double-blind, parallel-group study to evaluate the bioequivalence of QLHER2 and Herceptin in 60 subjects.Results:Following a 1.5-h intravenous infusion of single ascending doses of QLHER2 (1, 2, 4, or 6 mg/kg) In part I, Cmax and Tmax were 19.43-120.01 μg/mL and 68.91-157.87 h, respectively. AUC0-t and CL were 1.91-34.21 h*μg/mL and 0.54-0.12 ml/h/kg, indicating decreased clearance at higher doses, with a greater than proportional increase in the AUC0-t , and the t1/2 was 68.91-157.87 h. In part II, Plasma concentrations appeared to be comparable between QLHER2 and Herceptin over the 70-day sampling period and the QLHER2/Herceptin ratio of the Cmax and AUC0-t was 105.90% (90% CI: 95.69-117.26) and 95.79% (90% CI: 87.74-106.40%), respectively.Conclusion:The 90% CIs of the Cmax and AUC0-t for QLHER2/Herceptin ratio were within the range of 80.0-125.00% indicated that QLHER2 was bioequivalent to Herceptin. The results supported for further evaluation of QLHER2.Trial registration number: ChiCTR2000041577 and ChiCTR2100041802Date of registration: December 30,2020 and January 5, 2021

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Section: Discussionsupporting

confidence: 61%

A Comparative Pharmacokinetic Study to Evaluate the Bioequivalence and Safety of A Humanized Recombinant Monoclonal Antibody Targeting Human Epidermal Growth Factor Receptor 2 (HER2) with the Reference Herceptin in Healthy Chinese Subjects

Ding

Huang

Feng

et al. 2022

Preprint

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“…A study on SIBP-01, a biosimilar trastuzumab for HER2-overexpressing breast cancer, showed that the geometric mean ratios (90% CI) of C max , AUC 0-t and AUC inf were 93.55%–104.27%, 91.98%–102.35% and 91.88–102.34% respectively, they have PK similarity ( Zhou et al, 2020 ). And a research for a single intravenous infusion of 6 mg/kg of reference trastuzumab or its biosimilar DMB-3111 in healthy Japanese subjects showed their was bioequivalent ( Morita et al, 2016 ).…”

Section: Discussionmentioning

confidence: 99%

“…In another study of Unites States-trastuzumab (52 subjects) biosimilar HL02 (55 subjects), 19 subjects in both groups were ADA positive ( Zhang et al, 2021 ). A research in healthy Chinese male volunteers, the biosimilar SIBP-01 was compared with reference product Herceptin®, ADA was detected on the 35th day after administration ( Zhou et al, 2020 ). In this study, ADA was detected for the first time at 71st day after administration, the incidence of ADA in the two drugs was 30.0 and 32.5%, respectively.…”

Section: Discussionmentioning

confidence: 99%

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Pharmacokinetics, Immunogenicity and Safety Study for SHR-1309 Injection and Perjeta® in Healthy Chinese Male Volunteers

Cui

Ren

et al. 2021

Front. Pharmacol.

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Objectives: Pertuzumab is a monoclonal antibody for the treatment of breast cancer. The aim of this study was to compare the pharmacokinetics, immunogenicity and safety of the test preparation SHR-1309 injecta and the reference preparation Perjeta® in healthy Chinese male subjects.Methods: In this randomized, double-blind, single dose, two-way, parallel bioequivalence trial, a total of 80 qualified Chinese male subjects were selected and randomly divided into two groups. Each subject was intravenously injected with SHR-1309 or Perjeta®. Blood samples were collected at 21 different time points for pharmacokinetic analysis. In addition, immunogenicity was assessed at five different time points. The safety of the medication was monitored throughout the whole trial.Results: Cmax and AUC0-t were the primary pharmacokinetic parameters. Under a 90% confidence interval, their geometric mean ratios were 98.30 and 88.41% for SHR-1309 injection and Perjeta®, respectively. The geometric mean ratio of secondary pharmacokinetic parameters AUC0-∞ was 88.58%. These evaluation indexes are in the standard range of 80–125%, so SHR-1309 can be considered bioequivalent to Perjeta®. After 1,680 h (day 70) of administration, the two groups had 12 and 13 subjects who produced antidrug antibody (ADA), respectively. The occurrence time and proportion of ADA in SHR-1309 and Perjeta® were similar between subjects, and they had similar immunogenicity. During the entire trial period, there were 71 drug-related adverse reactions in 29 subjects who received SHR-1309 and 61 drug-related adverse reactions in 32 subjects who received Perjeta®. The incidence of adverse reactions between the two drugs was similar.Conclusion: The pharmacokinetic parameters, immunogenicity and safety of the biosimilar SHR-1309 injection produced by Shanghai Hengrui Pharmaceutical Co. Ltd. were similar to the original drug Perjeta® produced by Roche Pharma AG. The two drugs met the bioequivalence evaluation criteria. Therefore, SHR-1309 is bioequivalent to Perjeta®. Clinical trial registration: CTR20200,738.

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“…The protein molecular structure, biological activity, and purity of SIBP-01 are similar to those of Herceptin ® . However, the absence of a sufficient number of studies examining the bioequivalence of SIBP-01 with Herceptin ® in healthy individuals and patients with BC should be seriously considered [ 54 ].…”

Section: Resultsmentioning

confidence: 99%

Systematic Review on the Use of Biosimilars of Trastuzumab in HER2+ Breast Cancer

Triantafyllidi

Triantafillidis

2022

Biomedicines

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Trastuzumab is a monoclonal antibody used in the treatment of breast cancer in cases where the tumor overexpresses the HER2 receptor, a cell membrane receptor activated by the epidermal growth factor. Intravenous and subcutaneous administration of trastuzumab have comparable clinical and pharmacological characteristics, but trastuzumab biosimilars are currently only available in intravenous form. Trastuzumab biosimilars are ultimately preferred by a proportion of patients, especially in cases where co-administration of other chemotherapeutic agents, such as trastuzumab and tucatinib, a small molecule of tyrosine kinase inhibitor, is required in patients with HER-positive metastatic breast cancer. Oncologists should be well-aware of the advantages of intravenously administered trastuzumab biosimilars over subcutaneous administration, certainly also taking into account the patient’s preferences. Further cost-effectiveness analyses will be very important, along with expectations regarding successful concomitant subcutaneous administration of trastuzumab with other anticancer drugs, such as pertuzumab. This systematic review describes and analyzes the so-far published studies concerning the use of the available trastuzumab biosimilars in HER-positive early and metastatic breast cancer in terms of efficacy, safety, and cost–benefit ratio. An attempt was also made to draw some conclusions and to comment on future needs and perspectives.

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

Cited by 9 publications

References 19 publications

A Comparative Pharmacokinetic Study to Evaluate the Bioequivalence and Safety of A Humanized Recombinant Monoclonal Antibody Targeting Human Epidermal Growth Factor Receptor 2 (HER2) with the Reference Herceptin in Healthy Chinese Subjects

A Comparative Pharmacokinetic Study to Evaluate the Bioequivalence and Safety of A Humanized Recombinant Monoclonal Antibody Targeting Human Epidermal Growth Factor Receptor 2 (HER2) with the Reference Herceptin in Healthy Chinese Subjects

Pharmacokinetics, Immunogenicity and Safety Study for SHR-1309 Injection and Perjeta® in Healthy Chinese Male Volunteers

Systematic Review on the Use of Biosimilars of Trastuzumab in HER2+ Breast Cancer

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