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Efficacy and Safety of Denosumab Biosimilar QL1206 Versus Denosumab in Patients with Bone Metastases from Solid Tumors: A Randomized Phase III Trial

BACKGROUND: Denosumab has been approved for the treatment of bone metastases from solid tumors. QL1206 is the first denosumab biosimilar and needs to be compared with denosumab in a phase III trial. OBJECTIVE: This phase III trial aims to compare the efficacy, safety, and pharmacokinetics between QL...

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Autores principales: Li, Huiping, Huang, Yan, Chen, Zhendong, Zeng, Aiping, Zhang, Helong, Yu, Yan, Wei, Shihong, Li, Qingshan, Wang, Xiaojia, Wang, Xiangcai, Wang, Xiuwen, Yang, Runxiang, Dai, Xiumei, Bi, Minghong, Sun, Tao, Zhang, Qingyuan, Han, Cuicui, Li, Yujie, Kang, Xiaoyan, Liu, Yaxin, Zhang, Li
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer International Publishing 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9971153/
https://www.ncbi.nlm.nih.gov/pubmed/36802320
http://dx.doi.org/10.1007/s40259-023-00579-5
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author Li, Huiping
Huang, Yan
Chen, Zhendong
Zeng, Aiping
Zhang, Helong
Yu, Yan
Wei, Shihong
Li, Qingshan
Wang, Xiaojia
Wang, Xiangcai
Wang, Xiuwen
Yang, Runxiang
Dai, Xiumei
Bi, Minghong
Sun, Tao
Zhang, Qingyuan
Han, Cuicui
Li, Yujie
Kang, Xiaoyan
Liu, Yaxin
Zhang, Li
author_facet Li, Huiping
Huang, Yan
Chen, Zhendong
Zeng, Aiping
Zhang, Helong
Yu, Yan
Wei, Shihong
Li, Qingshan
Wang, Xiaojia
Wang, Xiangcai
Wang, Xiuwen
Yang, Runxiang
Dai, Xiumei
Bi, Minghong
Sun, Tao
Zhang, Qingyuan
Han, Cuicui
Li, Yujie
Kang, Xiaoyan
Liu, Yaxin
Zhang, Li
author_sort Li, Huiping
collection PubMed
description BACKGROUND: Denosumab has been approved for the treatment of bone metastases from solid tumors. QL1206 is the first denosumab biosimilar and needs to be compared with denosumab in a phase III trial. OBJECTIVE: This phase III trial aims to compare the efficacy, safety, and pharmacokinetics between QL1206 and denosumab in patients with bone metastases from solid tumors. METHODS: This randomized, double-blind, phase III trial was conducted in 51 centers in China. Patients aged 18–80 years, with solid tumors and bone metastases, and an Eastern Cooperative Oncology Group performance status of 0–2 were eligible. This study was divided into a 13-week double-blind period, a 40-week open-label period, and a 20-week safety follow-up period. In the double-blind period, patients were randomly assigned (1:1) to receive three doses of QL1206 or denosumab (120 mg subcutaneously every 4 weeks, each). Randomization was stratified by tumor types, previous skeletal-related events, and current systemic anti-tumor therapy. In the open-label period, up to ten doses of QL1206 could be given in both groups. The primary endpoint was percentage change in urinary N-telopeptide/creatinine ratio (uNTX/uCr) from baseline to Week 13. Equivalence margins were ± 0.135. Secondary endpoints included percentage change in uNTX/uCr at Week 25 and 53, percentage change in serum bone-specific alkaline phosphatase at Week 13, 25, and 53, and time to on-study skeletal-related events. The safety profile was evaluated based on adverse events and immunogenicity. RESULTS: From September 2019 to January 2021, in the full analysis set, 717 patients were randomly assigned to receive QL1206 (n = 357) or denosumab (n = 360). Median percentage changes in uNTX/uCr at Week 13 in two groups were − 75.2% and − 75.8%, respectively. Least-squares mean difference in the natural log-transformed ratio of uNTX/uCr at Week 13 to baseline between the two groups was 0.012 (90% confidence interval − 0.078 to 0.103), within the equivalence margins. There were no differences in the secondary endpoints between the two groups (all p > 0.05). Adverse events, immunogenicity, and pharmacokinetics were similar in the two groups. CONCLUSIONS: Denosumab biosimilar QL1206 had promising efficacy, tolerable safety, and pharmacokinetics equivalent to denosumab and could benefit patients with bone metastases from solid tumors. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04550949, retrospectively registered on 16 September, 2020 SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s40259-023-00579-5.
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spelling pubmed-99711532023-03-01 Efficacy and Safety of Denosumab Biosimilar QL1206 Versus Denosumab in Patients with Bone Metastases from Solid Tumors: A Randomized Phase III Trial Li, Huiping Huang, Yan Chen, Zhendong Zeng, Aiping Zhang, Helong Yu, Yan Wei, Shihong Li, Qingshan Wang, Xiaojia Wang, Xiangcai Wang, Xiuwen Yang, Runxiang Dai, Xiumei Bi, Minghong Sun, Tao Zhang, Qingyuan Han, Cuicui Li, Yujie Kang, Xiaoyan Liu, Yaxin Zhang, Li BioDrugs Original Research Article BACKGROUND: Denosumab has been approved for the treatment of bone metastases from solid tumors. QL1206 is the first denosumab biosimilar and needs to be compared with denosumab in a phase III trial. OBJECTIVE: This phase III trial aims to compare the efficacy, safety, and pharmacokinetics between QL1206 and denosumab in patients with bone metastases from solid tumors. METHODS: This randomized, double-blind, phase III trial was conducted in 51 centers in China. Patients aged 18–80 years, with solid tumors and bone metastases, and an Eastern Cooperative Oncology Group performance status of 0–2 were eligible. This study was divided into a 13-week double-blind period, a 40-week open-label period, and a 20-week safety follow-up period. In the double-blind period, patients were randomly assigned (1:1) to receive three doses of QL1206 or denosumab (120 mg subcutaneously every 4 weeks, each). Randomization was stratified by tumor types, previous skeletal-related events, and current systemic anti-tumor therapy. In the open-label period, up to ten doses of QL1206 could be given in both groups. The primary endpoint was percentage change in urinary N-telopeptide/creatinine ratio (uNTX/uCr) from baseline to Week 13. Equivalence margins were ± 0.135. Secondary endpoints included percentage change in uNTX/uCr at Week 25 and 53, percentage change in serum bone-specific alkaline phosphatase at Week 13, 25, and 53, and time to on-study skeletal-related events. The safety profile was evaluated based on adverse events and immunogenicity. RESULTS: From September 2019 to January 2021, in the full analysis set, 717 patients were randomly assigned to receive QL1206 (n = 357) or denosumab (n = 360). Median percentage changes in uNTX/uCr at Week 13 in two groups were − 75.2% and − 75.8%, respectively. Least-squares mean difference in the natural log-transformed ratio of uNTX/uCr at Week 13 to baseline between the two groups was 0.012 (90% confidence interval − 0.078 to 0.103), within the equivalence margins. There were no differences in the secondary endpoints between the two groups (all p > 0.05). Adverse events, immunogenicity, and pharmacokinetics were similar in the two groups. CONCLUSIONS: Denosumab biosimilar QL1206 had promising efficacy, tolerable safety, and pharmacokinetics equivalent to denosumab and could benefit patients with bone metastases from solid tumors. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04550949, retrospectively registered on 16 September, 2020 SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s40259-023-00579-5. Springer International Publishing 2023-02-21 2023 /pmc/articles/PMC9971153/ /pubmed/36802320 http://dx.doi.org/10.1007/s40259-023-00579-5 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by-nc/4.0/Open AccessThis article is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License, which permits any non-commercial use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc/4.0/ (https://creativecommons.org/licenses/by-nc/4.0/) .
spellingShingle Original Research Article
Li, Huiping
Huang, Yan
Chen, Zhendong
Zeng, Aiping
Zhang, Helong
Yu, Yan
Wei, Shihong
Li, Qingshan
Wang, Xiaojia
Wang, Xiangcai
Wang, Xiuwen
Yang, Runxiang
Dai, Xiumei
Bi, Minghong
Sun, Tao
Zhang, Qingyuan
Han, Cuicui
Li, Yujie
Kang, Xiaoyan
Liu, Yaxin
Zhang, Li
Efficacy and Safety of Denosumab Biosimilar QL1206 Versus Denosumab in Patients with Bone Metastases from Solid Tumors: A Randomized Phase III Trial
title Efficacy and Safety of Denosumab Biosimilar QL1206 Versus Denosumab in Patients with Bone Metastases from Solid Tumors: A Randomized Phase III Trial
title_full Efficacy and Safety of Denosumab Biosimilar QL1206 Versus Denosumab in Patients with Bone Metastases from Solid Tumors: A Randomized Phase III Trial
title_fullStr Efficacy and Safety of Denosumab Biosimilar QL1206 Versus Denosumab in Patients with Bone Metastases from Solid Tumors: A Randomized Phase III Trial
title_full_unstemmed Efficacy and Safety of Denosumab Biosimilar QL1206 Versus Denosumab in Patients with Bone Metastases from Solid Tumors: A Randomized Phase III Trial
title_short Efficacy and Safety of Denosumab Biosimilar QL1206 Versus Denosumab in Patients with Bone Metastases from Solid Tumors: A Randomized Phase III Trial
title_sort efficacy and safety of denosumab biosimilar ql1206 versus denosumab in patients with bone metastases from solid tumors: a randomized phase iii trial
topic Original Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9971153/
https://www.ncbi.nlm.nih.gov/pubmed/36802320
http://dx.doi.org/10.1007/s40259-023-00579-5
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