Efficacy, Safety, and Immunogenicity of HLX04 Versus Reference Bevacizumab in Combination with XELOX or mFOLFOX6 as First-Line Treatment for Metastatic Colorectal Cancer: Results of a Randomized, Double-Blind Phase III Study.

Colorectal cancer (CRC) is the third most common cancer worldwide. Approximately 20% of patients with CRC have metastases at their first visit. Bevacizumab is a biologic antibody approved in many countries for the treatment of metastatic CRC. However, high treatment costs significantly limit patient access to bevacizumab. Therefore, HLX04, a potential bevacizumab biosimilar, which is almost identical to bevacizumab but less expensive and more accessible, has been developed. This randomized clinical trial was designed to evaluate the efficacy (ability of a drug to produce the desired treatment effects), safety, and immunogenicity (ability of a drug to induce immune response that would affect its efficacy and safety) of HLX04 compared with the reference bevacizumab in patients with recurrent/metastatic CRC. Efficacy of the tested drug was evaluated by comparing the proportion of patients without disease progression or death at week 36 (PFSR_36w). Safety was monitored using adverse events and other clinical evaluations. Immunogenicity was assessed by the incidence of antidrug antibodies. Of the 677 patients enrolled in the study, 340 received HLX04 and 337 received bevacizumab. Statistical analyses showed that HLX04 was equivalent to bevacizumab in efficacy evaluations (the difference in PFSR_36w between the two treatment groups fell within the prespecified "equivalence margins"). Moreover, the two treatments were similar with respect to safety and immunogenicity evaluations. In summary, patients responded equally well to HLX04 and bevacizumab, supporting the development of HLX04 as a proposed biosimilar to bevacizumab for patients with recurrent/metastatic CRC.