FDA has granted a Priority Review designation for the breakthrough programmed death ligand-1 inhibitor atezolizumab, for the treatment of bladder cancer.
Following a review of the phase 2 results of the IMvigor 210 study, the FDA has granted a Priority Review designation for the breakthrough programmed death ligand-1 (PD-L1) inhibitor atezolizumab. Atezolizumab is designed to directly bind PD-L1 expressed on tumor cells and tumor-infiltrating immune cells, blocking its interactions with PD-1 and B7.1 receptors, thereby activating T-cells.
The phase 2 study of the drug assessed the safety and efficacy of atezolizumab in patients with locally advanced bladder cancer who had progressed on platinum-based chemotherapy, regardless of PD-L1 expression. Three-hundred and eleven patients were treated with 1200 mg of the drug on day 1 of 21-day cycles till they plateaued on clinical benefit, measured as objective response rate (ORR, defined by tumor shrinkage). The secondary endpoint was duration of response (DOR).
At 11.7 months, ORR was documented in 15% of patients, 26% of whom had medium and high levels of PD-L1 expression. At the time of this interim analysis, median DOR was not reached and 84% of participants had an ongoing response.
A point to note, however, is the low number of responders among the PD-L1—expressing patients, and that 84% of patients continued to respond independent of their PD-L1 expression.
According to Matthew Galsky, MD, study author and associate professor of Medicine, Hematology and Medical Oncology and assistant professor of Urology at Mount Sinai Hospital, “It is very difficult to imagine the clinical utility that this will have in the immediate term, given the lack of other good treatment options for bladder cancer.” Galsky, who spoke with OncLive, feels that the lack of other treatments in this space and the fact that the 10% response in non-expressers is as good as any other response observed in bladder cancer patients makes this a treatment to look forward to.
Biomarker-based treatment remains a challenge for immuno-oncology. While patients expressing the PD-1 receptor or those with mismatch repair deficiency seem to respond better to pembrolizumab, the response has been mixed with nivolumab.
According to Galsky, the FDA-label, once atezolizumab is approved, should be a better indicator of whether the drug is restricted for use in certain subsets of bladder cancer patients.
The PDUFA date for the drug is set for September 12, 2016.