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579 Background: Trastuzumab, an approved prescription drug by EMA and FDA under the name Herceptin has become the key treatment in patients with HER2−positive breast cancer. HD201, developed by Prestige Biopharma Pte Ltd is a biosimilar candidate to Herceptin. The biosimilarity of HD201 was established based on systematic stepwise comparisons between HD201 and reference product, Herceptin. In order to confirm clinical similarity of HD201 to Trastuzumab, two clinical studies were undertaken. Methods: First, in a double-blind, randomised and parallel group study, 101 randomised healthy human subjects were subjected to a single 6 mg/kg IV dose by body weight over 90-min infusion of either HD201, EU- and US-Herceptin group by assessing pharmacokinetic (PK) and safety (TROIKA-I). The second study was a randomised, double-blind, parallel group, equivalence, multicentre clinical phase III trial (TROIKA) designed to compare the efficacy based on total pathological complete response rate (tpCR), safety, and pharmacokinetics of HD201 to EU-Herceptin in patients with HER2 positive early breast cancer. Each group of ~250 subjects were administered with either HD201 or EU-Herceptin in combination with chemotherapy in neoadjuvant followed by the antibody alone in the adjuvant phase. Results: TROIKA-I study demonstrated that HD201 was safe and well tolerated with comparable PK as EU- and US-Herceptin. Based on the neoadjuvant data from TROIKA study, the tpCR rate in the HD201 and Herceptin treatment groups was comparable and the 95% CI was included within the pre-defined margins of equivalence (Table). The incidence and severity of reported TEAEs did not imply any significant safety concerns and were comparable between both groups. In addition, the comparison of steady-state Ctrough between both arms in TROIKA study has established equivalence. Conclusions: The overall comparison exercise demonstrated the equivalence of HD201 to Herceptin. Clinical trial information: 2016-0040019-11 . [Table: see text]

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Purpose This first-in-human study was designed to evaluate the pharmacokinetic (PK) equivalence between HD204 and the European Union (EU)-sourced bevacizumab, between HD204 and the United States of America (US)-sourced bevacizumab, and between EU-sourced and US-sourced bevacizumab (NCT 03390673). Methods In this randomized, double-blind, 3-way parallel group, single-dose comparative PK study, healthy male subjects were randomized to receive a single 1 mg/kg intravenous dose of HD204, EU-sourced bevacizumab or US-sourced bevacizumab. PK parameters were calculated using non-compartmental methods. PK equivalence was determined using the pre-defined equivalence margin of 0.8–1.25 in terms of AUC(0-∞) for the pairwise comparisons. Findings Baseline demographics for the 119 randomized subjects were similar across the three groups. The 90% CIs for the ratio of the geometric means of HD204 to US-sourced bevacizumab, HD204 to EU-sourced bevacizumab, and EU-sourced to US-sourced bevacizumab were all within the interval of 80% to 125% for AUC0-inf, thus demonstrating equivalency in the PK properties for all three treatment groups. Similarly, the ratio of the geometric means for AUC0-last and Cmax were all within the 80% and 125% margins, supporting the robustness of the primary findings. All other PK parameters, including the half-life (t1⁄2) clearance (CL), volume of distribution (Vd) and time of maximum concentration (tmax), were comparable. There was no difference between the 3 treatment arms in terms of vital signs, laboratory tests and adverse events. None of the subjects treated with HD204 had positive ADA results. Implications HD204 demonstrates equivalent pharmacokinetic profiles compared to those of both US-sourced and EU-sourced bevacizumab. (NCT 03390673).

e15014 Background: Prestige Biopharma Pte Ltd is developing HD204, a biosimilar of the EU-approved and US-licensed Bevacizumab (Avastin) that is approved treatment for a variety of tumour types. Bevacizumab is a recombinant humanized monoclonal antibody (IgG1) that binds to soluble vascular endothelial growth factor (VEGF), thus prevent interaction with VEGF receptors. Due to heterogeneity nature of antibody drug, extensive characterization of antibody from physicochemical and biological properties using multiple bioanalytical assays is required. The development of HD204 from analytical biocomparability to clinical trial I are demonstrated. Methods: Analytical biocomparability in physiocochemical and biological properties of HD204 was compared to Avastin sourced from EU and US using multiple bioanalytical assays as below. Clinical phase I (SAMSON), a randomized, double-blind, single dose and 3-way parallel group was initiated recently to compare pharmacokinetic and to evaluate the safety, tolerability and immunogenicity of HD204, EU-Avastin and US-Avastin. Approximately 120 healthy human subjects (assigned to 3 treatment group) was administered with a single intravenous infusion of 1 mg/kg of either HD204, EU- and US-Avastin. Results: HD204 shows equivalent in physicochemical and biological properties compared to EU- and US-Herceptin. For phase I study, patient recruitment was completed with treatment for come patients initiated but still ongoing. Conclusions: HD204 was shown to be equivalent in all parameters in the analytical biocomparability testing. Clinical Phase 1 trial (SAMSON) is ongoing on and key data from SAMSON trial will be reported in ASCO meeting. [Table: see text]