A Randomized Phase I Study Comparing the Pharmacokinetics of HD201, a Trastuzumab Biosimilar, With European Union–sourced Herceptin

Pivot, Xavier; Deslypère, J.P.; Park, Lisa Soyeon; Kim, Michael Jinwoo; Lee, Won–Jae; Lee, Jeonghyeon

doi:10.1016/j.clinthera.2018.01.009

Cited by 18 publications

(16 citation statements)

References 18 publications

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“…The difference was not statistically significant. The low incidence of ADA observed in this study is consistent with previously reported data on trastuzumab [14,21,22]. These data indicate low immunogenicity of SIBP-01 and trastuzumab.…”

Section: Discussionsupporting

confidence: 93%

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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

Zhou

Cao

Zhu

et al. 2020

Expert Opinion on Drug Metabolism & Toxicology

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Objectives: This study aimed to evaluate the bioequivalence, safety, tolerability and immunogenicity of the biosimilar trastuzumab (SIBP-01) compared to Herceptin®. Methods: In this Phase I randomized double-blind parallel-group trial, 100 healthy male volunteers were randomized in a1:1 ratio to receive a single 6 mg•kg-1 intravenous dose of SIBP-01 or Herceptin®. Serum concentrationswere analyzed using a validated ELISA. Results: The two groups had similar baseline characteristics. The geometric mean ratios (90% CI) of C max , AUC 0-t and AUC inf between the trial group and the reference group were 93.55%-104.27%, 91.98%-102.35% and 91.88%-102.34%, respectively; the geometric mean ratios (90% CI) of AUC 0-t and AUC inf in the sensitivity analysis were 92.29%-102.63% and 91.81%-102.16%, respectively. These values were within the prespecified equivalence margins, establishing the bioequivalence of SIBP-1 and Herceptin®. AEs were similar across all subjects in the SIBP-01 and Herceptin® arms, with treatmentrelated AEs reported by 72.00% and 80.00%, respectively. In each group, there was one AE that caused a subject to discontinue the study. Expert opinion: Trastuzumab (Herceptin®) is significantly more effective than chemotherapy in reducing exacerbations and tumor cell growth, and its adverse events are far lower than chemotherapy. Herceptin®is very expensive for most patients in China. The protein molecular primary structure of the biosimilar trastuzumab (SIBP-01) is consistent with Herceptin®, with highly similar high level structure, biologocal activity and purity.But there are few studies comparing the bioequivalence of SIBP-01 and Herceptin® in healthy subjects and cancer patients. Conclusions: This study showed the PK similarity of SIBP-01 to Herceptin®. SIBP-01 was safe and well tolerated in healthy male volunteers, with no significant differences from the reference drug in safety or immunogenicity.

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Section: Discussionsupporting

confidence: 93%

“…In this trial, the safety and immunogenicity of SIBP-01 and Herceptin® in PK were similar, which is in accordance with previous studies on trastuzumab [12][13][14]. These data support the continued development of SIBP-01 as a potential drug similar to trastuzumab.…”

Section: Discussionsupporting

confidence: 89%

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

Zhou

Cao

Zhu

et al. 2020

Expert Opinion on Drug Metabolism & Toxicology

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“…HVs have recently been enrolled in studies evaluating biosimilars to originator biologics such as trastuzumab [ 62 ]. Studies in HVs can be used to assess PK bioequivalence and to compare the immunogenicity of a biosimilar with that of the originator biologic [ 63 ].…”

Section: Characterizing the Clinical Pharmacology Of Anticancer Drugsmentioning

confidence: 99%

Reviewing the role of healthy volunteer studies in drug development

Karakunnel¹,

Bui²,

Palaniappan

et al. 2018

J Transl Med

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BackgroundWith the exception of genotoxic oncology drugs, first-in-human, Phase 1 clinical studies of investigational drugs have traditionally been conducted in healthy volunteers (HVs). The primary goal of these studies is to investigate the pharmacokinetics and pharmacodynamics of a novel drug candidate, determine appropriate dosing, and document safety and tolerability.Main bodyWhen tailored to specific study objectives, HV studies are beneficial to manufacturers and patients alike and can be applied to both non-oncology and oncology drug development. Enrollment of HVs not only increases study accrual rates for dose-escalation studies but also alleviates the ethical concern of enrolling patients with disease in a short-term study at subtherapeutic doses when other studies (e.g. Phase 2 or Phase 3 studies) may be more appropriate for the patient. The use of HVs in non-oncology Phase 1 clinical trials is relatively safe but nonetheless poses ethical challenges because of the potential risks to which HVs are exposed. In general, most adverse events associated with non-oncology drugs are mild in severity, and serious adverse events are rare, but examples of severe toxicity have been reported. The use of HVs in the clinical development of oncology drugs is more limited but is nonetheless useful for evaluating clinical pharmacology and establishing an appropriate starting dose for studies in cancer patients. During the development of oncology drugs, clinical pharmacology studies in HVs have been used to assess pharmacokinetics, drug metabolism, food effects, potential drug–drug interactions, effects of hepatic and renal impairment, and other pharmacologic parameters vital for clinical decision-making in oncology. Studies in HVs are also being used to evaluate biosimilars versus established anticancer biologic agents.ConclusionA thorough assessment of toxicity and pharmacology throughout the drug development process is critical to ensure the safety of HVs. With the appropriate safeguards, HVs will continue to play an important role in future drug development.

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“…Pivot et al 65 also conducted a phase 1 pharmacokinetic study on another trastuzumab biosimilar candidate (HD201) comparing with Herceptin, showing equivalence results in the pharmacokinetics between HD201 and the reference trastuzumab. The study will be followed by a new phase 3 study to assess the efficacy, safety, and immunogenicity of HD201 associated with docetaxel for the treatment of HER2 positive breast cancer.…”

Section: Biosimilar Drugs In Oncologymentioning

confidence: 99%

Can biosimilar products be interchangeable? Pharmaceutical perspective in the implementation of biosimilars in oncology

Soares

Cavalcanti

Vasconcelos

2021

J Oncol Pharm Pract

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Objective To evaluate the safety in the interchangeability of biosimilar products approved for cancer treatment from a pharmaceutical perspective. Methods A literature review was carried out using the descriptors “Biosimilar”, “Oncology Therapy”, “Interchangeable drugs” and “Biological Products”, in the Sciencedirect, MEDLINE, and CAPLUS databases. Results Fifty-one articles were selected, which addressed the importance of establishing standards that prove the efficacy and safety of biosimilars with reference products, as well as the growing interest of the pharmaceutical industry in the development of biosimilars and the impact on costs and changes in the perspective of the treatment of cancer patients. Conclusions As they are large and complex molecules, it is impossible to obtain identical copies of their reference products, which generates conflicts and concerns on the part of the pharmaceutical class regarding the safety in the interchangeability of these products, highlighting the importance of pharmacovigilance in this process.

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A Randomized Phase I Study Comparing the Pharmacokinetics of HD201, a Trastuzumab Biosimilar, With European Union–sourced Herceptin

Cited by 18 publications

References 18 publications

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

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

Reviewing the role of healthy volunteer studies in drug development

Can biosimilar products be interchangeable? Pharmaceutical perspective in the implementation of biosimilars in oncology

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