The US Food and Drug Administration has accepted the priority application for atezolizumab (MPDL3280A), an investigational targeted agent for patients with locally advanced or metastatic urothelial carcinoma.
The US Food and Drug Administration (FDA) has accepted the priority application for atezolizumab (MPDL3280A), an investigational targeted agent for patients with locally advanced or metastatic urothelial carcinoma (mUC) who had disease progression during or following platinum-based chemotherapy in the metastatic setting, or whose disease worsened after neoadjuvant or after adjuvant therapy.
On March 14, 2016, the FDA accepted the company’s Biologics License Application (BLA) and granted Priority Review for this investigational monoclonal antibody. This paves the way for this agent being approved within the next 6 months for this patient population.
"Atezolizumab was granted Priority Review designation based on results of the IMvigor 210 study, which showed the medicine shrank tumors in a type of advanced bladder cancer, and the majority responding to treatment continued to respond after nearly a year of follow-up," said Sandra Horning, MD, chief medical officer and head of Global Product Development for Genentech, in a press release.
Dr. Horning said that the treatment options available for advanced bladder cancer are very limited and Genentech is committed to working with the FDA to bring the first anti-PDL1 cancer immunotherapy to patients with this disease as quickly as possible. Atezolizumab was granted Breakthrough Therapy Designation by the FDA in May 2014 for the treatment of patients whose metastatic bladder cancer expresses PD-L1.
The IMvigor 210 phase II study evaluated the safety and efficacy of atezolizumab in patients with locally advanced or mUC, regardless of PD-L1 expression. A total of 311 patients whose disease had progressed during or following previous treatment with a platinum-based chemotherapy regimen received a 1,200 mg intravenous dose of atezolizumab on day one of 21-day cycles until loss of clinical benefit. The primary endpoint of the study was objective response rate (ORR).
The findings, which were published in the Lancet, showed durable activity and good tolerability. In addition, increased levels of PD-L1 expression on immune cells were associated with increased response. This study is the first to demonstrate an association of The Cancer Genome Atlas (TCGA) subtypes with response to immune checkpoint inhibition and to show the importance of mutation load as a biomarker of response to this class of agents in bladder cancer.
The investigators found that atezolizumab shrank tumors (ORR) in 15% of patients whose disease progressed after platinum-based chemotherapy in an updated analysis based on 11.7 months of median follow-up. Atezolizumab shrank tumors in 26% of patients whose disease had medium and high levels of PD-L1 expression.
The most common grade 3 to 4 treatment-related adverse events included fatigue (2%), decreased appetite, pyrexia, anemia, ALT and AST increase, arthralgia, dyspnea, pneumonitis, colitis, hypertension, and hypotension (all were 1%). There were no treatment-related grade 5 adverse events.
The FDA is expected to make a decision on approval by September 12, 2016. Atezolizumab also is being studied in a number of other cancers, including lung cancer.