The FDA has accepted a supplemental biologics license application (sBLA) for atezolizumab (Tecentriq, Genentech) and has granted the product priority review for the treatment of patients with locally advanced or metastatic urothelial carcinoma who are ineligible for cisplatin chemotherapy, and who are either previously untreated (first-line) or have disease progression at least 12 months after receiving chemotherapy before surgery (neoadjuvant) or after surgery (adjuvant). The FDA will make a decision on approval by April 30, 2017.

Atezolizumab is a monoclonal antibody designed to bind with the programmed death ligand-1 (PD-L1) protein on tumor cells and tumor-infiltrating immune cells, blocking its interactions with both programmed death-1 (PD-1) and B7.1 receptors. By inhibiting PD-L1, atezolizumab may enable the activation of T cells. The antibody may also affect normal cells.

The sBLA submission for atezolizumab was based on results from the phase 2, open-label, multicenter, single-arm IMvigor210 trial, which evaluated the safety and efficacy of atezolizumab in patients with locally advanced or metastatic urothelial carcinoma, regardless of PD-L1 expression.

The subjects were enrolled into one of two cohorts. Cohort 1, upon which the sBLA submission was based, consisted of patients who were ineligible for first-line cisplatin-based chemotherapy, and who had received no prior chemotherapies for locally advanced or metastatic urothelial carcinoma (i.e., first-line) or had disease progression at least 12 months after neoadjuvant or adjuvant chemotherapy. Cohort 2, which served as the basis for the FDA’s accelerated approval of atezolizumab in May 2016, included patients whose disease had progressed during or after previous treatment with a platinum-based chemotherapy regimen, or who had disease progression within 12 months of treatment with a platinum-based neoadjuvant or adjuvant chemotherapy regimen.

The study’s primary endpoint was objective response rate. Secondary endpoints included the duration of response, overall survival, progression-free survival, and safety.

Atezolizumab is currently approved by the FDA to treat patients with locally advanced or metastatic urothelial carcinoma who have disease progression during or after platinum-based chemotherapy or whose disease has worsened within 12 months of neoadjuvant or adjuvant platinum-based chemotherapy. Atezolizumab is also approved for the treatment of patients with metastatic non–small-cell lung cancer who have disease progression during or after platinum-containing chemotherapy and have progressed on an appropriate FDA-approved targeted therapy if their tumor has EGFR or ALK gene abnormalities.

Urothelial carcinoma accounts for 90% of all bladder cancers and can also be found in the renal pelvis, ureter, and urethra. The American Cancer Society has estimated that more than 79,000 Americans will be diagnosed with bladder cancer in 2017. 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. Approximately 96% of patients will live five or more years when diagnosed with the earliest stage of the disease, compared with 39% when diagnosed in advanced stages (III–IV) of the disease. Men are approximately three to four times more likely to develop bladder cancer during their lifetimes than women.

Source: Genentech; January 8, 2017.

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