590P - A double-blind, randomized, parallel group study to demonstrate the equivalent pharmacokinetic properties of a single intravenous dose HD201, a trastuzumab biosimilar candidate, versus EU trastuzumab and US trastuzumab

Background

PharmaPrestige Co., Ltd. (Singapore) has developed HD201, a biosimilar candidate of the reference trastuzumab product. Among the stepwise approach to ensure comparability between the biosimilar candidate and the reference medical product, a phase I in healthy subjects is recommended to demonstrate the pharmacokinetic (PK) equivalence. We report the results of this phase I trial (NCT03776240).

Methods

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-minute i.v. infusion to healthy male subjects. A pairwise comparisons based on 3 co-primary endpoints including AUC_0-inf , C_max and AUC_0-last were undertaken. PK equivalence was to be concluded if the 90% confidence interval for the ratio of geometric means for each criterion were within the conventional equivalence margin of 80% to 125%. Secondary objectives included assessment of other PK parameters, safety, tolerability, and immunogenicity in the 3 arms.

Results

A total of 105 healthy male subjects were randomized in this study. Pairwise comparisons for all PK criteria of judgements in all groups provided confident intervals included between the margins of equivalence. PK profiles including t_{1/2 ,} V_d ,Cl and T_max were similar across treatments. The frequency of subjects with adverse events 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%). The commonest adverse events related to treatment were infusion related reactions and administration site reactions.

Conclusions

Overall, HD201 demonstrates equivalent PK to both EU-Herceptin® and US-Herceptin®. A large randomized study (TROIKA) aimed to demonstrate a similar activity in neoadjuvant setting for early breast cancer is on going (NCT03013504).

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

Prestige Pharma.

Funding

Prestige Pharma.

Disclosure

J. Chung Shii Hii: Full/Part-time employment: employees of PrestigeBioPharma. P. Feyaerts: Full/Part-time employment: PrestigeBioPharma. F. Ang: Full/Part-time employment: employees of PrestigeBioPharma. J. Litha: Full/Part-time employment: employees of PrestigeBioPharma. F. Deforce: Full/Part-time employment: dice. M.P. Derde: Full/Part-time employment: Deice. M. Kim: Full/Part-time employment: employees of PrestigeBioPharma. L. Park: Full/Part-time employment: employees of PrestigeBioPharma. P. Xavier: Honoraria (institution): Prestige Pharma. All other authors have declared no conflicts of interest.