U.S. Food and Drug Administration Approval Summary: Atezolizumab for Metastatic Non–Small Cell Lung Cancer

Abstract

On October 18, 2016, the FDA approved atezolizumab (TECENTRIQ; Genentech, Inc.) for treatment of patients with metastatic non-small cell lung cancer (mNSCLC) whose disease progressed during or following platinum-containing chemotherapy. Approval was based on demonstration of clinically meaningful improvements in overall survival (OS) and an acceptable safety profile in two randomized clinical trials (OAK and POPLAR). Median OS in OAK, a phase III trial, was 13.8 months [95% confidence interval (CI), 11.8-15.7] in the atezolizumab arm compared with 9.6 months (95% CI, 8.6-11.2) in the docetaxel arm [hazard ratio (HR) = 0.74; 95% CI, 0.63-0.87; = 0.0004]. Median OS in POPLAR, a phase II trial, was 12.6 months (95% CI, 9.7-16.0) and 9.7 months (95% CI, 8.6-12.0; HR = 0.69; 95% CI, 0.52-0.92) for the atezolizumab and docetaxel arms, respectively. In patients treated with atezolizumab, the most common (≥20%) adverse reactions were fatigue, decreased appetite, dyspnea, cough, nausea, musculoskeletal pain, and constipation; the most common (≥2%) grade 3 to 4 adverse events were dyspnea, pneumonia, hypoxia, hyponatremia, fatigue, anemia, musculoskeletal pain, aspartate aminotransferase increase, alanine aminotransferase increase, dysphagia, and arthralgia. Clinically significant immune-related adverse events for patients receiving atezolizumab included 1.4% incidence each of grade 3 to 4 pneumonitis, hepatitis, colitis, and thyroid disease..

Elimination of tumor by CD47/PD-L1 dual-targeting fusion protein that engages innate and adaptive immune responses

“…Atezolizumab (TECENTRIQ Ò ), a phage-derived human IgG 1 antibody targeting PD-L1, has been shown to have anti-tumor activity in non-clinical assays and in clinical studies, and was first approved by the US Food and Drug Administration in May 2016. 6,22 Relative to wild-type SIRPa, CV1 is an engineered highaffinity SIRPa variant, with affinity to CD47 » 50,000-fold increased, which exhibited remarkable synergy with all tumorspecific mAbs tested by increasing phagocytosis in vitro and enhancing antitumor responses in vivo. 15 In this study, we constructed an innate and adaptive immunity-dependent bispecific fusion protein(denoted as IAB) based on the variable region of atezolizumab and CV1 monomer in a IgG 1 backbone using "Knobs-into-holes" technology (as shown in Fig.…”

Cytologic‐histologic correlation of programmed death‐ligand 1 immunohistochemistry in lung carcinomas

“…For the majority of patients who have advanced NSCLC without a targetable driver mutation, the mainstay of therapy for the past 3 decades has been combination platinum‐based cytotoxic chemotherapy . Immunotherapy is being used increasingly, and since 2015, the US Food and Drug Administration has approved 3 new checkpoint inhibitors that target the programmed cell death protein 1 (PD‐1) receptor for the treatment of patients with advanced NSCLC: nivolumab, pembrolizumab, and atezolizumab …”

“…4,5 Immunotherapy is being used increasingly, and since 2015, the US Food and Drug Administration has approved 3 new checkpoint inhibitors that target the programmed cell death protein 1 (PD-1) receptor for the treatment of patients with advanced NSCLC: nivolumab, pembrolizumab, and atezolizumab. 6 The PD-1 receptor is a type I transmembrane cell receptor expressed primarily on activated mature T cells, B cells, monocytes, and other components of the immune system. 7 Binding of PD-1 to its ligands, programmed death-ligand 1 (PD-L1) or PD-L2, results in the inhibition of T-cell receptor-mediated lymphocyte proliferation through a variety of mechanisms, acting as a limiting factor in inflammatory responses and a mediator of peripheral tolerance.…”

Hyperprogression and Immune Checkpoint Inhibitors: Hype or Progress?

“…The Oncologist 2020;25: [94][95][96][97][98] Immunotherapy in the form of checkpoint blockade has resulted in impressive responses for several previously refractory tumor types. Indeed, the U.S. Food and Drug Administration (FDA) has now approved seven checkpoint inhibitors: pembrolizumab, nivolumab, durvalumab, avelumab, atezolizumab, cemiplimab, and ipilimumab [1][2][3][4][5][6][7]. Immune checkpoint inhibitors mediate responses by reactivating the immune system.…”