TROIKA-1: A double-blind, randomized, parallel group, study aimed to demonstrate the equivalent pharmacokinetic profile of HD201, a potential biosimilar candidate to trastuzumab, versus EU-Herceptin® and US-Herceptin® in healthy male subjects

Martin Demarchi, Pierre Coliat, Kristi Mclendon, Jocelyn Chung Shii Hii, Peggy Feyaerts, Felicia Ang, Litha Jaison, Filip Deforce, Marie Paule Derde, Michael Jinwoo Kim, Lisa Soyeon Park, Alexandre Detappe, Xavier Pivot, Martin Demarchi, Pierre Coliat, Kristi Mclendon, Jocelyn Chung Shii Hii, Peggy Feyaerts, Felicia Ang, Litha Jaison, Filip Deforce, Marie Paule Derde, Michael Jinwoo Kim, Lisa Soyeon Park, Alexandre Detappe, Xavier Pivot

Abstract

Prestige Biopharma Ltd (Singapore) has developed HD201, a proposed biosimilar to reference product trastuzumab. As a part of the stepwise approach to ensure comparability between the biosimilar candidate and the reference medicinal product, a phase I study in healthy subjects was conducted to demonstrate the pharmacokinetic (PK) equivalence (NCT03776240). The primary objective of the study was to demonstrate (PK) equivalence of HD201, EU-Herceptin® , and US-Herceptin® given at 6 mg/kg as a 90-min i.v. infusion to healthy male subjects. A pairwise comparisons based on the primary endpoint AUC0-inf and secondary PK endpoints, AUC0-last and Cmax were undertaken. PK equivalence was to be concluded if the 90% confidence interval (CI) for the ratio of geometric means for each criterion were within the equivalence margin of 80% to 125%. Secondary objectives included assessment of other PK parameters, safety, tolerability, and immunogenicity in the three arms. A total of 105 healthy male subjects (35/treatment) were randomized in this study. The 90% CI for the ratios of AUC0-inf , Cmax and AUC0-last , were within 80%-125% for the comparisons of HD201 to EU-Herceptin® or US-Herceptin® and EU-Herceptin® to US-Herceptin® . The frequency of subjects with TEAEs of special interest was slightly lower in the HD201 group (20.0%) compared to the other treatment groups (EU-Herceptin® : 34.3%; US-Herceptin® : 31.4%). Only 1 subject (EU-Herceptin® group) developed anti-drug antibodies prior to dosing. Overall, HD201 demonstrates PK similarity to both EU-Herceptin® and US-Herceptin® . The three study drugs also demonstrated similar safety profiles.

Keywords: biosimilar; pharmacokinetic; trastuzumab.

Conflict of interest statement

Martin Demarchi, Pierre Coliat, Xavier Pivot, Kristi Mclendon, and Alexandre Detappe do not have any conflicts of interest for this article.

Jocelyn Chung Shii Hii, Peggy Feyaerts, Felicia Ang, and Litha Jaison were employees of Prestige Biopharma Ltd Singapore Michael Jinwoo Kim, Lisa Soyeon Park, were employees of Prestige Biopharma Ltd Singapore and Prestige Biologics Co Ltd, Korea.

Marie Paule Derde and Filip Deforce were employees by DICE Ltd which had a memorandum of understanding with Prestige Biopharma Ltd.

© 2021 The Authors. Pharmacology Research & Perspectives published by British Pharmacological Society and American Society for Pharmacology and Experimental Therapeutics and John Wiley & Sons Ltd.

Figures

FIGURE 1
FIGURE 1
Subject disposition in TROIKA‐1 study. PKC population considered all subjects with PK samples collection. PKP population considered all subjects with full samples collection allowing the determination of PK parameters. N = number of subjects in the group ; n = number of subjects meeting specific criteria
FIGURE 2
FIGURE 2
Trastuzumab serum concentration–time profiles (PKC population). Mean (±SD) trastuzumab concentrations over time are shown for all three groups on a linear scale (upper panel) and a semi‐logarithmic scale (lower panel). Insets show zoom of the first 48 hours after end of infusion. Number of subjects with serum concentrations reported at each time are provided in the source table. Note: Mean trastuzumab concentrations = 0.0 µg/L are not plotted on the semi‐logarithmic graph; some error bars are not shown on the semi‐logarithmic graph as negative values cannot be plotted logarithmically. The curves were based on the PKC concentration with 34, 35 and 32 subjects in the HD201, EU‐herceptin and US‐herceptin groups respectively

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