An interim analysis of 61 sufferers with UC in this study indicated that durvalumab was well tolerated and associated with antitumor activity, particularly in patients with PD-L1-high disease (25% of tumor cells [TCs] or tumor-infiltrating immune cells expressing PD-L1), resulting in its breakthrough therapy designation by the US Food and Drug Administration (FDA)

An interim analysis of 61 sufferers with UC in this study indicated that durvalumab was well tolerated and associated with antitumor activity, particularly in patients with PD-L1-high disease (25% of tumor cells [TCs] or tumor-infiltrating immune cells expressing PD-L1), resulting in its breakthrough therapy designation by the US Food and Drug Administration (FDA). We report a planned analysis of the safety and efficacy of durvalumab in patients with locally advanced/metastatic UC from this phase 1/2 study. the UC Cohort by PD-L1 expression status (as-treated population) eFigure 3. Time to onset of first any-grade treatment-related AEs and AESIs in the UC cohort and overall 10 mg/kg Q2W population jamaoncol-3-4454-s002.pdf (645K) GUID:?766B2F63-48ED-4452-8251-8C32A1B23522 Key Points Question Does durvalumab provide clinical benefit to patients with locally advanced or metastatic urothelial carcinoma (UC)? Findings In a phase 1/2 open-label study of 191 patients with locally advanced/metastatic UC, confirmed objective response rate with durvalumab, 10 mg/kg every 2 weeks, was 17.8%, including 7 complete responses, and median progression-free survival and overall survival were 1.5 and 18.2 months, respectively. Grade 3/4 treatment-related and immune-mediated adverse events occurred in 13 patients (6.8%) and 4 patients (2.1%), respectively. Meaning Durvalumab shows favorable efficacy and an excellent safety profile in patients with locally advanced/metastatic UC. Abstract Importance The data reported herein were accepted for assessment by the US Food and Drug Administration for Biologics License Application under priority review to establish the clinical benefit of durvalumab as second-line therapy for locally advanced or metastatic urothelial carcinoma (UC), resulting in its recent US approval. Objective To report a planned update of the safety and efficacy of durvalumab in patients with locally advanced/metastatic UC. Design, Setting, and Participants This is an ongoing phase 1/2 open-label study of 191 adult patients with histologically or cytologically confirmed locally advanced/metastatic UC whose disease had progressed on, were ineligible for, or refused prior chemotherapy from 60 sites in 9 countries as reported herein. Intervention Patients were administered durvalumab intravenous infusion, 10 mg/kg every 2 weeks, for up to 12 months or until progression, starting another anticancer therapy, or unacceptable toxic effects. Main Outcomes and Measures Primary end points were safety and confirmed objective response rate (ORR) per blinded independent central review (Response Evaluation Criteria In Solid Tumors [RECIST], version 1.1). Results A total of 191 patients with UC had received treatment. As of October 24, 2016 (90-day update), the median follow-up was 5.78 months (range, 0.4-25.9 months). The median age of patients was 67.0 years and most were male (136 [71.2%]) and white (123 [71.1%]). All patients had stage 4 disease, and 190 (99.5%) had prior anticancer therapy (182 [95.3%] postplatinum). The ORR was 17.8% (34 AM 0902 of 191; 95% CI, 12.7%-24.0%), including 7 complete responses. Responses were early (median time to response, 1.41 months), AM 0902 durable (median duration of response not reached), and observed regardless of programmed cell death ligand-1 (PD-L1) expression (ORR, 27.6% [n?=?27; 95% CI, 19.0%-37.5%] and 5.1% [n?=?4; 95% CI, 1.4%-12.5%] in patients with high and low or negative expression of PD-L1, respectively). Median progression-free survival and overall survival were 1.5 months (95% CI, 1.4-1.9 months) and 18.2 months (95% CI, 8.1 months to not estimable), respectively; AM 0902 the 1-year overall survival rate was 55% (95% CI, 44%-65%), as estimated by Kaplan-Meier method. Grade 3/4 treatment-related adverse events (AEs) occurred in 13 patients (6.8%); grade 3/4 immune-mediated AEs occurred in 4 patients (2.1%); and treatment-related AEs led to discontinuation of 3 patients (1.6%), 2 of whom had immune-mediated Slc7a7 AEs that led to death (autoimmune hepatitis and pneumonitis). Conclusions and Relevance Durvalumab, 10 mg/kg every 2 weeks, demonstrates favorable clinical activity and an encouraging and manageable safety profile in patients with locally advanced/metastatic UC. Trial Registration clinicaltrials.gov Identifier: “type”:”clinical-trial”,”attrs”:”text”:”NCT01693562″,”term_id”:”NCT01693562″NCT01693562 Introduction Outcome for patients who relapse after chemotherapy for stage 4 urothelial carcinoma (UC) is poor. Optimal second-line chemotherapy remains undefined. As such, there is a significant unmet need for therapies that are well tolerated AM 0902 and confer clinical benefit in this population. Recent encouraging data with immune checkpoint inhibitors have resulted in positive randomized phase 3 studies and regulatory approvals. The presence of tumor-infiltrating mononuclear cells is associated with longer.