The Food and Drug Administration (FDA) has approved Imfinzi (durvalumab; AstraZeneca) 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. The indication is approved under accelerated approval based on tumor response rate and duration of response; continued approval is contingent upon verification and description of clinical benefit in confirmatory trials.
The approval of Imfinzi was based on one single-arm trial which included 182 patients with locally advanced or metastatic urothelial cancer whose disease progressed after prior platinum-containing chemotherapy. All patients received Imfinzi 10mg/kg via intravenous infusion every 2 weeks for up to 12 months or until unacceptable toxicity or disease progression. Tumor assessments were performed at Weeks 6, 12 and 16, then every 8 weeks for the first year and every 12 weeks thereafter. The major efficacy outcome measures were confirmed Objective Response Rate (ORR) according to RECIST v1.1 as assessed by Blinded Independent Central Review (BICR), and duration of response (DoR). Tumor specimens were evaluated prospectively for PD-L1 expression on tumor cells and immune cells at a central laboratory using the FDA-approved Ventana PD-L1 (SP263) Assay (Ventana Medical Systems, Inc.).
Among the 182 patients, the confirmed ORR was 17% (95% CI: 11.9, 23.3). At the data cutoff for the ORR analysis, median response DoR was not reached (range: 0.9+ to 19.9+ months). The confirmed ORR was 26.3% (95% CI: 17.8, 36.4) in patients with a high PD-L1 score (n=95) and 4.1% (95% CI: 0.9, 11.5) in patients with a low or negative PD-L1 score (n=73); samples for 14 patients were not evaluable. The most common adverse effects reported included fatigue, musculoskeletal pain, constipation, decreased appetite, nausea, peripheral edema, and urinary tract infection.
Durvalumab is a human immunoglobulin G1 kappa (IgG1κ) monoclonal antibody that blocks the interaction of PD-L1 with PD-1 and CD80 (B7.1). Blockade of PD-L1/PD-1 and PD-L1/CD80 interactions releases the inhibition of immune responses, without inducing antibody dependent cell-mediated cytotoxicity (ADCC). PD-L1 blockade with durvalumab led to increased T-cell activation in vitro and decreased tumor size in co-engrafted human tumor and immune cell xenograft mouse models.
Imfinzi will be available in single-dose vials in 500mg/10mL or 120mg/2.4mL strengths.
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