A randomized, double-blind, parallel-group, single-dose comparative pharmacokinetic study of DRL_TZ, a candidate biosimilar of trastuzumab, with Herceptin (EU) in healthy adult males.

Background & Objectives: Trastuzumab (TZ) is a recombinant DNA-derived humanized monoclonal antibody approved for human epidermal growth factor receptor 2 positive early breast cancer, metastatic breast and gastric cancers. For the development of TZ biosimilars, establishing pharmacokinetic equivalence is required. The primary objective of this study was to compare the pharmacokinetics (PK) of Dr Reddy's Laboratories TZ (DRL_TZ) with that of EU-approved Reference Medicinal Product (RMP), Herceptin in healthy adult male subjects.

Methods: In this double-blind, parallel-group, phase I study (TZ-01-003), healthy male subjects aged 18-55 yr were randomized 1:1 to receive a single intravenous infusion of 6 mg/kg of TZ as DRL_TZ or RMP. Similarity for primary PK parameters was defined as the 90 per cent confidence intervals (CIs) for the geometric mean ratios (GMRs) falling within 75-133 per cent limits. Primary endpoints included area under the concentration-time curve - from time zero (pre-dose) to the last quantifiable concentration [AUC] and from time zero (pre-dose) extrapolated to infinity [AUC], and maximum observed serum concentration (C). Secondary objectives were to compare the safety and immunogenicity of DRL_TZ with that of the RMP.

Results: Thirty two subjects were dosed (DRL_TZ, 16; RMP, 16). Primary PK parameters were found to be comparable with their 90 per cent CIs for the GMR falling within the usual more stringent limits of 80-125 per cent. The number of subjects reporting at least one TEAE in both the arms was similar. No serious adverse events were reported. Fifteen subjects, eight in DRL_TZ arm and seven in Herceptin arm, tested positive for anti-drug antibodies (ADAs), none of the ADAs were neutralizing in nature.

Interpretation & Conclusions: In this study, DRL_TZ demonstrated PK equivalence with the RMP and had comparable safety and immunogenicity profiles in healthy adult male subjects.