Clinical studies of Atezolizumab contributing to FDA approvals

Abstract

PD-1/PD-L1 pathway mediates human self-tolerance, but tumours can achieve immune resistance by usurping PD-1/PD-L1 pathway and inhibiting antitumor response in vivo. PD-L1 antibody is proved to enhance immune function in tumour tissue by blockade of PD-1/PD-L1 interaction. Genentech inc. developed MPDL3280A (atezolizumab), a humanized monoclonal PD-L1 antibody with reduced Fc effector function via a single amino acid substitution. PD-L1 antibody drugs generally have good curative effects and less adverse events comparing to PD-1 antibody drug, but there’re prerequisites such as PD-L1 expression and T cell infiltration in tumor tissues. PD-L1 won’t induce ideal antitumour activity in most of the cases lacking proper pathological conditions. This review aims at providing an overview for crucial clinical stages of atezolizumab before its approvals, as a reference for future development of atezolizumab or other PD-L1 antibodies development. Patient populations, methods, results and safety information of one basic phase I clinical trial and three specialized phase III clinical trials that has led to the three approvals of atezolizumab by FDA were summarized and stated briefly.