The Food and Drug Administration (FDA) has granted an accelerated approval to the PD-L1 inhibitor Imfinzi (durvalumab) for the treatment of patients with locally advanced or metastatic urothelial carcinoma who have disease progression during or following platinum-containing chemotherapy or who have disease progression within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy.
A complementary diagnostic for PD-L1, the VENTANA PD-L1 (SP263) Assay, was simultaneously approved.
The approval was based on a single-arm trial that included 182 patients with locally advanced or metastatic urothelial carcinoma who experienced disease progression following platinum-containing chemotherapy. Patients received Imfinzi at 10 mg/kg IV every 2 weeks.
The objective response rate (ORR) per blinded independent central review was 17 percent. At the data cutoff, the median duration of response was not reached.
Using the VENTANA PD-L1 (SP263) Assay, response was also evaluated by PD-L1 status. Among 95 patients with high PD-L1 expression the ORR was 26.3 percent. In the cohort of 73 patients with low or no PD-L1 expression, the ORR was 4.1 percent.
All grade adverse events (AEs) occurring in 15 percent or more of patients included fatigue, musculoskeletal pain, constipation, decreased appetite, nausea, swelling caused by fluid and urinary tract infection.
Grade 3/4 AEs occurred in 43 percent of patients. Infection and immune-related AEs observed with Imfinzi included pneumonitis, hepatitis, colitis, thyroid disease, adrenal insufficiency and diabetes.
In February 2016, the FDA granted a breakthrough therapy designation to Imfinzi as a treatment for patients with PD-L1–positive inoperable or metastatic urothelial bladder cancer following progression on prior treatment with a platinum-based regimen.
The accelerated approval of Imfinzi in bladder cancer is contingent upon results from a confirmatory trial.
Imfinzi is also being evaluated as a single agent and in combination with tremelimumab in the phase 3 DANUBE trial in the frontline setting for patients with metastatic urothelial carcinoma, regardless of their eligibility for cisplatin-based chemotherapy.
More than 30 other ongoing trials are evaluating various combinations of Imfinzi with other immunotherapies and targeted agents.