Atezolizumab Wins Priority Review Designation for Urothelial Carcinoma

FDA approval decision expected in September

The FDA has accepted the biologics license application (BLA) for atezolizumab (Roche/Genentech) and has granted priority review for the treatment of patients with locally advanced or metastatic urothelial carcinoma who had disease progression during or after 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).

A priority review designation is given to medications that the FDA has determined to have the potential to provide significant improvements in the prevention or diagnosis of a serious disease. The agency is expected to make a decision on approval by September 12, 2016.

Atezolizumab is an investigational monoclonal antibody designed to bind with PD-L1. The antibody is designed to bind directly to PD-L1 expressed on tumor cells and tumor-infiltrating immune cells, thereby blocking interactions with PD-1 and B7.1 receptors. By inhibiting PD-L1, atezolizumab may enable the activation of T cells. Atezolizumab may also affect normal cells.

The BLA submission was based on results from the phase 2, open-label, single-arm IMvigor 210 trial, which evaluated the safety and efficacy of atezolizumab in patients with locally advanced or metastatic urothelial carcinoma regardless of PD-L1 expression. A total of 311 patients whose disease had progressed during or after treatment with a platinum-based chemotherapy regimen received a 1,200-mg intravenous dose of atezolizumab on day 1 of 21-day cycles until the loss of clinical benefit. The study’s primary endpoint was the objective response rate (ORR), as determined by the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. Secondary endpoints included the duration of response (DOR), overall survival, progression-free survival, and safety.

In an updated analysis based on a median follow-up period of 11.7 months, atezolizumab shrank tumors (ORR) in 15% of 310 patients evaluable for efficacy and safety whose disease progressed after platinum-based chemotherapy. Atezolizumab shrank tumors in 26% of 100 patients whose disease had medium or high levels of PD-L1 expression. Median DOR was not reached at the time of analysis; with a median follow-up period of 11.7 months, 84% (38/45) of patients had an ongoing response.

The most common grade-3 to grade-4 treatment-related adverse events included fatigue (2%), decreased appetite, pyrexia, anemia, increased alanine aminotransferase (ALT) and aspartate aminotransferase (AST), arthralgia, dyspnea, pneumonitis, colitis, hypertension, and hypotension (all 1%). There were no treatment-related grade-5 adverse events.

Urothelial carcinoma accounts for 90% of all bladder cancers and can also be found in the renal pelvis, ureter, and urethra. According to the American Cancer Society (ACS), more than 76,000 Americans will be diagnosed with bladder cancer in 2016, and approximately 11% of new diagnoses are made when bladder cancer is in advanced stages. There is a dramatic difference in survival rates between early and advanced bladder cancer. The ACS estimates that approximately 96% of people will live five or more years when diagnosed with the earliest stage of the disease, compared with 39% when diagnosed in advanced stages (stage III–IV). Men are approximately three to four times more likely to get bladder cancer during their lifetimes than women.

In addition to IMvigor 210, Genentech is conducting an ongoing, confirmatory phase 3 study (IMvigor 211) comparing atezolizumab with chemotherapy in patients whose bladder cancer has progressed on at least one prior platinum-containing regimen.

Source: Roche; March 15, 2016.