Safety and Efficacy of Durvalumab (MEDI4736) an Anti Programmed Cell Death Ligand 1 Immune Checkpoint Inhibitor, in Patients With Advanced Urothelial Bladder Cancer.
PURPOSE To investigate the safety and efficacy of durvalumab, a human monoclonal antibody that binds programmed cell death ligand 1 (PD L1) and the role of PD L1 expression on clinical response in patients with advanced urothelial bladder cancer (UBC) METHODS A phase 1/2 multicenter, open label study is being conducted in patients with inoperable or metastatic solid tumors. We report here the results from the UBC expansion cohort. Durvalumab (MEDI4736, 10 mg/kg every 2 weeks) was administered intravenously for up to 12 months. The primary end point was safety, and objective response rate (ORR, confirmed) was a key secondary end point. An exploratory analysis of pretreatment tumor biopsies led to defining PD L1 positive as 25% of tumor cells or tumor infiltrating immune cells expressing membrane PD L1. RESULTS A total of 61 patients (40 PD L1 positive, 21 PD L1 negative) 93.4% of whom received one or more prior therapies for advanced disease, were treated (median duration of follow up, 4.3 months) The most common treatment related adverse events (AEs) of any grade were fatigue (13.1% diarrhea (9.8% and decreased appetite (8.2% Grade 3 treatment related AEs occurred in three patients (4.9% there were no treatment related grade 4 or 5 AEs. One treatment related AE (acute kidney injury) resulted in treatment discontinuation. The ORR was 31.0% (95% CI, 17.6 to 47.1) in 42 response evaluable patients, 46.4% (95% CI, 27.5 to 66.1) in the PD L1 positive subgroup, and 0% (95% CI, 0.0 to 23.2) in the PD L1 negative subgroup. Responses are ongoing in 12 of 13 responding patients, with median duration of response not yet reached (range, 4.1+ to 49.3+ weeks) CONCLUSION Durvalumab demonstrated a manageable safety profile and evidence of meaningful clinical activity in PD L1 positive patients with UBC, many of whom were heavily pretreated.
Journal of clinical oncology official journal of the American Society of Clinical Oncology