FDA grants priority review to Roche’s atezolizumab in urothelial carcinoma

The US Food and Drug Administration (FDA) has accepted Roche’s Biologics License Application (BLA) and granted priority review for atezolizumab (anti-PDL1; MPDL3280A) for the treatment of people with locally advanced or metastatic urothelial carcinoma (mUC).

Specifically, the BLA is for the treatment of patients 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 (neoadjuvant) or after surgery (adjuvant).

The BLA submission and priority review is based on results of the IMvigor 210 Phase II study. IMvigor 210 evaluated the safety and efficacy of atezolizumab in people with locally advanced or mUC, regardless of PD-L1 expression. People in the study whose disease had progressed during or following previous treatment with a platinum-based chemotherapy regimen received a 1200-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) as assessed by an independent review facility (IRF) using Response Evaluation Criteria in Solid Tumours (RECIST) v1.1. Secondary endpoints included duration of response (DOR), overall survival, progression-free survival and safety.

In an updated analysis based on 11.7 months of median follow up, atezolizumab shrank tumours (ORR) in 15 percent of people evaluable for efficacy and safety (n=310) whose disease progressed after platinum-based chemotherapy. Atezolizumab shrank tumours in 26 percent of people whose disease had medium and high levels of PD-L1 expression. Median DOR was not reached at the time of analysis; with a median duration of follow up of 11.7 months, 84 percent of people had an ongoing response. The most common Grade 3 to 4 treatment-related adverse events included: fatigue, decreased appetite, pyrexia, anaemia, enzymes in the blood (ALT and AST increase), arthralgia, dyspnea, pneumonitis, colitis, hypertension and hypotension. There were no treatment-related Grade 5 adverse events.

FDA expected to make a decision on atezolizumab by 12 September 2016

“Atezolizumab was granted Priority Review designation based on results of the IMvigor 210 study, which showed the medicine shrank tumours 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, M.D., Chief Medical Officer and Head of Global Product Development at Roche. “The treatment options available for advanced bladder cancer are very limited, and we are committed to working with the FDA to bring the first anti-PDL1 cancer immunotherapy to people with this disease as quickly as possible.”

A Priority Review designation is granted to medicines that the FDA has determined to have the potential to provide significant improvements in the safety and effectiveness of the treatment, prevention or diagnosis of a serious disease. The FDA will make a decision on approval by mid-September 2016.