A randomized, double-blind, single-dose study to evaluate the biosimilarity of QL1101 with bevacizumab in healthy male subjects

Liu, Yanan; Huang, Jie; Guo, Chenchen; Yang, Shuang; Ye, Ling; Wu, Shu‐Lin; Zhang, Xing-Fei; Yang, Xiaoyan; Han, Cheol; Pei, Qi; He, Qing; Yang, Guoping

doi:10.1007/s00280-019-04014-x

Cited by 12 publications

(17 citation statements)

References 21 publications

(25 reference statements)

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“…Moreover, results confirm that bevacizumab-EU and bevacizumab-US are bioequivalent to each other, consistent with results from other phase I studies of bevacizumab biosimilars [16,17]. The PK results of this study are consistent with those of other phase I PK studies of (proposed) bevacizumab biosimilars which also demonstrated equivalence to the reference product [16][17][18][19][20][21][22][23][24][25][26]. However, direct comparisons of absolute PK parameters values between studies are generally not appropriate due to differences between the doses used (1 mg/kg, 3 mg/kg or 5 mg/kg), sample collection, and assessment methods [16][17][18][19][20][21][22][23][24][25][26].…”

Section: Discussionsupporting

confidence: 89%

A phase I, randomized, single-dose pharmacokinetic study comparing sb8 (bevacizumab biosimilar) with reference bevacizumab in healthy volunteers

Shin

Lee

Choi

et al. 2020

Cancer Chemother Pharmacol

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Purpose To compare pharmacokinetics, safety, tolerability, and immunogenicity between SB8, a bevacizumab biosimilar, and the European Union (EU) and United States (US) reference products (bevacizumab-EU, bevacizumab-US). Methods In this randomized, double-blind, parallel-group, and single-dose study, healthy volunteers were randomized to receive a 3 mg/kg dose of SB8, bevacizumab-EU, or bevacizumab-US via intravenous infusion. Primary endpoints were area under the concentration–time curve from time zero to infinity (AUCinf) and to the last quantifiable concentration (AUClast), and maximum observed serum concentration (Cmax). Bioequivalence was achieved if 90% confidence intervals (CIs) for the ratios of the geometric least squares means (LSMeans) of primary endpoints were within the predefined bioequivalence margins of 80.00–125.00%. Safety and immunogenicity were also investigated. Results The 90% CIs for the geometric LSMean ratios of AUCinf, AUClast and Cmax were all within the prespecified bioequivalence margins. Geometric LSMean ratios for SB8/bevacizumab-EU, SB8/bevacizumab-US and bevacizumab-EU/bevacizumab-US were 88.01%, 88.48% and 100.54% for AUCinf, 88.65%, 89.08% and 100.49% for AUClast and 99.59%, 101.15% and 101.56% for Cmax, respectively. Incidence of treatment-emergent adverse events (TEAEs) across treatment groups was comparable (SB8: 50.0%, bevacizumab-EU: 37.5%, bevacizumab-US: 53.8%). Most TEAEs were mild and considered as not related to the study drug. No deaths or treatment discontinuations due to adverse events occurred. Incidence of anti-drug antibodies was also comparable between all groups and no neutralizing antibodies were detected. Conclusion This study demonstrated pharmacokinetic bioequivalence and similar safety and immunogenicity profiles of SB8 to both reference products, bevacizumab-EU and bevacizumab-US, and of bevacizumab-EU to bevacizumab-US. Clinicaltrials.gov identifier NCT02453672 (submitted date); EudraCT number: 2015-001,026-41.

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Section: Discussionsupporting

confidence: 89%

A phase I, randomized, single-dose pharmacokinetic study comparing sb8 (bevacizumab biosimilar) with reference bevacizumab in healthy volunteers

Shin

Lee

Choi

et al. 2020

Cancer Chemother Pharmacol

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“…The mean t 1/2 of HOT-1010 and Avastin ® was 14.6 d and 14.9 days, which was consistent with the results of other bevacizumab biosimilars (13.1-19.3 days) in Chinese, Indian, Caucasian and Korean healthy male subject studies (Knight et al, 2016;Zhang et al, 2018;Wang et al, 2019;Liu et al, 2020;Shin et al, 2020;Singh et al, 2020). The median T max of HOT-1010 (3.48 h) was similar to that of bevacizumab and other bevacizumab biosimilars (2.5-4.5 h) when intravenous dose ranged from 1 to 3 mg/kg (Zhang et al, 2018;Wang et al, 2019;Liu et al, 2020;Shin et al, 2020;Singh et al, 2020). HOT-1010 was well-tolerated and no safety concerns were identified, and safety profiles were similar between HOT-1010 group and Avastin ® group.…”

Section: Discussionsupporting

confidence: 84%

“…The most common TEAEs (more than 5% incidence) included increased blood triglycerides, increased alanine aminotransferase, increased aspartate aminotransferase, hyperuricemia, decreased blood fibrinogen, increased conjugated bilirubin, increased blood creatine phosphokinase and proteinuria. TEAEs reported in this study were almost expected, based on previous studies in healthy subjects and tumor patients (Genentech Inc, 2015;Liu et al, 2020;Wang et al, 2019). All subjects with TEAEs had recovered.…”

Section: Discussionsupporting

confidence: 73%

“…Although the exact mechanisms are not clear yet, these AEs of HOT-1010 should be paid more attention in the future study. Additionally, 82 subjects were found to be negative for ADA test, other studies also showed the relatively low immunogenicity of bevacizumab (Knight et al, 2016;Zhang et al, 2018;Wang et al, 2019;Liu et al, 2020;Shin et al, 2020;Singh et al, 2020), the comparison of immunogenicity still needs to be further investigated with larger sample size.…”

Section: Discussionmentioning

confidence: 99%

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A Randomized, Double-Blind, Single-Dose Study Comparing the Biosimilarity of HOT-1010 With Bevacizumab (Avastin®) in Chinese Healthy Male Subjects

et al. 2021

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Objective: This study was conducted to compare the pharmacokinetics, safety and immunogenicity of HOT-1010 with bevacizumab (Avastin®) in Chinese healthy male subjects.Methods: A single-center, randomized, double-blind, single-dose, parallel trial was performed in 84 Chinese healthy male subjects who randomly (1:1) received a single intravenous infusion of 1 mg/kg HOT-1010 or Avastin® for 90 min and followed up for 85 days. Serum concentrations of bevacizumab were analyzed by enzyme-linked immunosorbent assay. Primary pharmacokinetic parameters, Cmax, AUC0-t and AUC0-∞, were calculated and evaluated the bioequivalence between HOT-1010 and Avastin®, the safety and immunogenicity of investigational drugs were also assessed.Results: A total of 82 subjects completed the study. The 90% Confidence Intervals for geometric mean ratios of Cmax, AUC0-t and AUC0-∞ were 91.81–103.64%, 85.19–95.39% and 85.04–95.36%, which were all within the bioequivalence margin. Treatment-emergent adverse events were reported in 27 (65.9%) subjects in HOT-1010 group and 23 (56.1%) subjects in Avastin® group. Most TEAEs were mild or moderate. No TEAEs, Serious Adverse Events or deaths leading to discontinuation was reported. Subjects were all tested negative for Anti-drug Antibody.Conclusion: HOT-1010 exhibited the similar pharmacokinetics, safety and immunogenicity profiles of bevacizumab (Avastin®) in Chinese healthy male subjects.Clinical Trial Registration:http://www.chinadrugtrials.org.cn/index.html, CTR20181610.

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“…Since NMPA launched “Guidelines for the research, development and technique assessment of biosimilar drugs (Trial)” in 2015 [15] , 49 trials involving bevacizumab biosimilars have emerged. QL1101 (ChiCTR1900022767) [40] and IBI305 (NCT02954172) [41] were approved by NMPA on Dec 18th, 2019 and June 19th, 2020, respectively.…”

Section: Discussionmentioning

confidence: 99%

The changing landscape of anti-lung cancer drug clinical trials in mainland China from 2005 to 2020

Zhong

Tao

Chen

et al. 2021

The Lancet Regional Health - Western Pacific

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Background In recent years, new drug development on lung cancer is in full swing in China. The aim of this study was to overview the changing landscape of anti-lung cancer drug clinical trials in mainland China from 2005 to 2020. Methods We analysed anti-lung cancer drug clinical trials registered on three websites including the China National Medical Products Administration Centre for Drug Evaluation platform, the Chinese Clinical Trial Registry and ClinicalTrials.gov. Findings A total of 1595 anti-lung cancer drug clinical trials from Jan 1st, 2005 to Dec 31st, 2020 were extracted, which included 630 (39•5%) investigator-initiated trials (IITs), 698 (43•8%) domestic industry-sponsored trials (ISTs), and 267 (16•7%) international ISTs. During the past 16 years, the number of anti-lung cancer clinical trials including IITs and domestic ISTs had a remarkable growth, however, the number of international ISTs increased slowly. The number of principal clinical trial units also increased significantly over time. Of the 1595 trials, the largest growth was observed in phase I trials during 2013–2020, with an average annual growth rate of 38•6%. 278 trials were led by principal investigators (PI) from Guangdong, followed by Beijing ( n =273) and Shanghai ( n =257). Among the 965 ISTs, clinical trials involving targeted drugs (588, 60•9%) accounted for the largest proportion, followed by immunotherapeutic drugs (284, 29•4%), cytotoxic drugs (75, 7•8%), and traditional Chinese medicine (18, 1•9%). In terms of targeted drugs, EGFR-TKIs remained the most studied drugs (225/588, 38•27%). As for immunotherapy, 125 out of 284 (44•01%) trials involved PD-1 inhibitors, 60 (21•13%) trials involved PD-L1 inhibitors, and seven (2•46%) trials involved CTLA-4 inhibitors. Interpretation In the past 16 years, the development of anti-lung cancer drug clinical trials has achieved much progress in mainland China. The most progress lied in targeted therapy and immunotherapy. Funding This work was financially supported in part by China National Major Project for New Drug Innovation (2017ZX09304015) and Chinese Academy of Medical Sciences (CAMS) Innovation Fund for Medical Sciences (CIFMS) (2016-I2M-1-001).

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A randomized, double-blind, single-dose study to evaluate the biosimilarity of QL1101 with bevacizumab in healthy male subjects

Cited by 12 publications

References 21 publications

A phase I, randomized, single-dose pharmacokinetic study comparing sb8 (bevacizumab biosimilar) with reference bevacizumab in healthy volunteers

A phase I, randomized, single-dose pharmacokinetic study comparing sb8 (bevacizumab biosimilar) with reference bevacizumab in healthy volunteers

A Randomized, Double-Blind, Single-Dose Study Comparing the Biosimilarity of HOT-1010 With Bevacizumab (Avastin®) in Chinese Healthy Male Subjects

The changing landscape of anti-lung cancer drug clinical trials in mainland China from 2005 to 2020

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