Updated results from the phase I/II trial showed an objective response rate of 20.4% in all evaluable patients (n = 103, 95% confidence interval [CI] = 13.1%–29.5%) and 31.1% (95% CI = 19.9%–44.3%) in patients whose tumors expressed programmed cell death ligand 1 (PD-L1). At the time of data cutoff, median overall survival was 14.1 months (95% CI = 4.7 to not estimable).
David Berman, Senior Vice President, Head of Oncology Innovative Medicines at MedImmune, said, “The durable responses observed in this larger data set from Study 1108 confirm the promising efficacy we’ve already seen for durvalumab in patients with advanced bladder cancer. We are continuing to test durvalumab in combination with tremelimumab and as monotherapy in the bladder cancer first-line setting in our ongoing phase III DANUBE trial.”
Durvalumab at 10 mg/kg was administered intravenously every 2 weeks for up to 12 months and demonstrated a manageable safety profile among all patients (n = 191). The most common adverse events reported in 5% or more of patients were fatigue (19.4%), decreased appetite (9.4%), diarrhea (8.4%), rash (7.3%), nausea (6.8%), arthralgia (5.8%), pyrexia (5.8%), and pruritus (5.2%). Grade 3 or 4 adverse events occurred in 6.8% of patients, and 3 patients discontinued treatment due to adverse events.
Thomas Powles, MD, MBBS, MRCP, Director of Barts Cancer Institute and first author of the abstract, said, “The clinical efficacy of durvalumab in patients with advanced urothelial carcinoma is particularly encouraging. For the past 3 decades we’ve seen limited progress in therapy for bladder cancer patients, and there remains significant unmet need for new treatment options.”
In December 2016, AstraZeneca received U.S. Food and Drug Administration (FDA) acceptance of review of the Biologics License Application (BLA) for durvalumab in patients with locally advanced or metastatic urothelial carcinoma whose disease has progressed during or after one standard platinum-based regimen. The drug was granted Priority Review.
The urothelial cancer cohort from Study 1108 formed the basis for the BLA submission, which follows the FDA’s Breakthrough Therapy designation for durvalumab in the treatment of patients with PD-L1–positive inoperable or metastatic urothelial bladder cancer whose disease has progressed during or after one standard platinum-based regimen.