The FDA has accepted a biologics license application (BLA) and granted a priority review designation for atezolizumab (Genentech) for the treatment of patients with locally advanced or metastatic non–small-cell lung cancer (NSCLC) whose disease expresses programmed death ligand-1 (PD-L1) proteins, as determined by an FDA-approved test, and who have progressed on or after platinum-containing chemotherapy.
Atezolizumab is an investigational monoclonal antibody designed to directly bind to PD-L1 proteins expressed on tumor cells and tumor-infiltrating immune cells, thereby blocking interactions of these proteins with PD-1 and B7.1 receptors. By inhibiting PD-L1 proteins, atezolizumab may enable the activation of T cells. The treatment may also affect normal cells.
Atezolizumab was granted a breakthrough therapy designation by the FDA in February 2015 for the treatment of patients whose NSCLC expresses PD-L1 and whose disease has progressed during or after standard treatments, such as platinum-based chemotherapy and appropriate targeted therapy for epidermal growth factor receptor (EGFR) mutation-positive or anaplastic lymphoma kinase (ALK)-positive disease.
This is the second BLA acceptance and priority review for atezolizumab. In March, the FDA accepted the BLA and granted priority review for atezolizumab for the treatment of patients with locally advanced or metastatic urothelial carcinoma who experienced disease progression during or after platinum-based chemotherapy in the metastatic setting, or whose disease worsened within 12 months of receiving platinum-based chemotherapy before surgery (neoadjuvant) or after surgery (adjuvant). Atezolizumab is also being studied in several other cancers.
The new BLA submission for atezolizumab was based on results from clinical studies, including the BIRCH trial. BIRCH was a phase 2, open-label, multicenter, single-arm study that evaluated the safety and efficacy of atezolizumab in 667 patients with locally advanced or metastatic NSCLC whose disease expressed PD-L1. PD-L1 expression was assessed for both tumor cells and tumor-infiltrating immune cells with an investigational immunohistochemistry (IHC) test based on the SP142 antibody. The subjects received a 1,200-mg intravenous dose of atezolizumab every three weeks. The primary endpoint was the objective response rate (ORR), as determined by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Secondary endpoints included the duration of response, progression-free survival (PFS), overall survival (OS), and safety.
The study met its primary endpoint and showed that atezolizumab shrank tumors (ORR) in up to 27% (P = 0.0001) of subjects with the highest PD-L1 levels whose disease had progressed on prior medications. When atezolizumab was administered as first-line treatment in this cohort, 48% of the subjects experienced six-month PFS, and the OS rate at six months was 79%.
The FDA will make a decision on whether to approve atezolizumab by October 19, 2016.