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The U.S. Food and Drug Administration has granted priority review designation to atezolizumab (MPDL3280A) for the treatment of 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 within 12 months of receiving platinum-based chemotherapy before surgery or after surgery.

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The FDA's priority review designation shortens the time to complete a drug's review and aims to deliver a decision on marketing approval designation for drugs that may offer major advances in treatment or provide a treatment where no adequate therapy exists within six months under the Prescription Drug User Fee Act (PDUFA). The FDA action date for atezolizumab for this indication is September 12.


Previous FDA Actions for atezolizumab

Atezolizumab has previously received breakthrough therapy designation for the treatment of patients with metastatic bladder cancer that expresses the protein PD-L1 (OT 6/25/14 issue). The drug has also previously received breakthrough therapy designation for the treatment of patients with PD-L1 positive non-small cell lung cancer whose disease has progressed during or after platinum-based chemotherapy (OT 2/25/15 issue).


Phase II and III Trials to Determine Safety, Efficacy

This designation for atezolizumab is based on data from the open-label, multicenter, single-arm Phase II IMvigor 210 study that evaluated the safety and efficacy of atezolizumab in patients with locally advanced or metastatic urothelial cancer, regardless of PD-L1 expression.


In an updated analysis based on 11.7 months of median follow up, treatment with atezolizumab shrank tumors in 15 percent of the patients show disease progressed after platinum-based chemotherapy. Atezolizumab shrank tumors in 26 percent of patients whose disease had medium and high levels of PD-L1 expression. And median duration of response was not reached at the time of analysis.


The most common grade 3 to 4 treatment-related adverse events included: fatigue, decreased appetite, pyrexia, anemia, enzymes in the blood, arthralgia, dyspnea, pneumonitis, colitis, hypertension, and hypotension. There were no treatment-related grade 5 adverse events.


A confirmatory Phase III study (IMvigor 211) is also ongoing in patients with bladder cancer that has progressed on at least one prior platinum-containing regimen.


The trial is comparing treatment with atezolizumab with treatment with chemotherapy.


The drug is being developed by Genentech.