Results of a phase I clinical trial of cetuximab biosimilar (RPH-002).

Abstract

e18036 Background: Hyperexpression of the human epidermal growth factor receptor (EGFR) is observed in a number of cancers, including head and neck cancer and colorectal cancer. Erbitux is a recombinant, chimeric monoclonal antibody that binds to the extracellular domain of EGFR and blocks signal transduction through this receptor. RPH-002 is a biosimilar to Erbitux. This study investigated the pilot efficacy of RPH-002 in comparison with Erbitux in patients with advanced head and neck squamous cell carcinoma (HNSCC). Methods: CL01002062 was a multicenter, open-label, randomized phase I study. The objective of the study was to establish the equivalence of the pharmacokinetic (PK) properties, safety and immunogenicity of RPH-002 and Erbitux, as well as to evaluate the pilot efficacy in patients with advanced HNSCC in combination with docetaxel and cisplatin as 1 st line therapy. Cetuximab was administered intravenously at a dose of 250 mg/m 2 (loading dose 400 mg/m 2 ) Q1W in combination with cisplatin 75 mg/m 2 and docetaxel 75 mg/m 2 Q3W until progression or intolerable toxicity. Primary PK endpoint was AUC (0-168) , AUC tau ss was also assessed. As part of the pilot efficacy assessment objective response rate (ORR) and disease control rate (DCR) were analyzed according to RECIT 1.1 criteria determined by Independent Radiology Review Committee in ITT population. As part of the final analysis, immunogenicity was assessed over 4.5 months of therapy. Results: 118 patients were randomized in 2 groups (n=55 in RPH-002 group and n=63 in Erbitux group). The number of patients with unresectable locoregional recurrence of HNSCC after primary combination treatment and patients with newly diagnosed advanced HNSCC was comparable between therapy groups (p=0.824). The median age was 61 years (range 32–86). The majority of patients had Karnofsky index 80-90% – 93.22%. Most of the subjects (78.81%) had progressed after previous therapy. The 94.12% CI for the ratio of the geometric mean values of AUC (0-168) of RPH-002 to AUC (0-168) of Erbitux was 89.17% - 107.87%. The 90% CI for the ratio of the geometric mean values of AUC tau ss of RPH-002 to AUC tau ss of Erbitux was 97.76% - 114.23%. No ADA to cetuximab were detected during the entire observation period. ORR in ITT population was 27.27% [95% CI: 17.28; 40.23] in RPH-002 group and 28.57% [95% CI: 18.9; 40.7] in Erbitux group (p = 1.000). DCR in ITT population was 67.27% [95% CI: 54.10; 78.19] in RPH-002 group and 77.78% [95% CI: 66.09; 86.27] in Erbitux group (p = 0.283). ORR in PP population was 36.84% [95% CI: 23.38; 52.72] in RPH-002 group and 33.33% [95% CI: 22.24; 46.64] in Erbitux group (p = 0,900). DCR in PP population was 86.84% [95% CI: 72.67; 94.25] in RPH-002 group and 90.74% [95% CI: 80.09; 95.98] in Erbitux group (p = 0,801). Conclusions: RPH-002 has similar PK, safety and efficacy profiles in comparison with Erbitux. Clinical trial information: CT No557 (06.11.2018) .