Genentech recently announced the results of a Phase II study entitled BIRCH for the investigational cancer immunotherapy atezolizumab (MPDL3280A; anti-PDL1). Primary endpoints for BIRCH study investigating the therapeutic benefit of atezolizumab in patients with a specific type of lung cancer – locally advanced or metastatic non-small cell lung cancer (NSCLC) – were successfully completed with atezolizumab administration, resulting in tumor shrinkage. Additionally, the study showed that patients’ tumor cells’ PD-L1 expression correlated with disease severity and response to atezolizumab treatment.
Atezolizumab is an under-investigation monoclonal antibody designed to specifically target the protein programmed death-ligand 1 (PD-L1), also known as cluster of differentiation 274 (CD274) or B7 homolog 1 (B7-H1). The protein is expressed in tumor cells as a strategy to inhibit activation of immune system effector cells. Specifically, when PD-L1 binds to its receptors – PD-1 and B7.1 – located at the surface of immune system T cells, it leads to T cells’ inactivation, creating an immunosuppressive environment where tumors can survive and grow. Atezolizumab binding to PD-L1 in tumor cells and tumor-infiltrating immune cells prevents PD-L1 binding to its receptors, thereby enabling the activation of T cells, as well as recruiting other immune cells to attack the tumor.
The BIRCH study enrolled 667 patients with locally advanced or metastatic NSCLC whose tumor cells and tumor-infiltrating immune cells expressed PD-L1. Patients were treated with 1200 milligram doses of atezolizumab, administered intravenously every three weeks. The study’s secondary endpoints included duration of response (DoR), overall survival (OS), progression-free survival (PFS) and safety.
Sandra Horning, M.D., chief medical officer and head of Global Product Development, commented on the study findings: “We are encouraged by the number of people who responded to atezolizumab and maintained their response during the study, which is particularly meaningful for people who had received several prior treatments. We plan to present results at an upcoming medical meeting and will discuss these data as well as results from our other lung cancer studies with health authorities to bring this medicine to patients as quickly as possible.”
Atezolizumab is currently being evaluated in eleven 11 Phase III studies (ongoing or initiating in a near future) in several types of cancer, including lung, kidney, breast and bladder cancer.