Cabozantinib Plus Durvalumab in Patients With Advanced Urothelial Carcinoma After Platinum Chemotherapy: Safety and Preliminary Activity of the Open-Label, Single-Arm, Phase 2 ARCADIA Trial

Background: Durvalumab and cabozantinib have shown single-agent activity in patients with metastatic urothelial carcinoma (UC). ARCADIA is a phase 2 study evaluating their combination in patients with platinum-treated, advanced UC (NCT03824691). Herein, we report the results of the planned interim safety analysis and the preliminary activity. Patients and Methods: Patients with Eastern Cooperative Oncology Group Performance Status (ECOG PS) 0 or 1, UC and non-UC histology, and failure of a maximum of two regimens received cabozantinib 40 mg daily, orally, in combination with durvalumab 1500 mg, intravenously, every 28 days. Response was evaluated by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 every two cycles and by fluorodeoxyglucose positron emission tomography (FDG-PET) scans. Results: As of August 20, 2020, 16 patients were enrolled with a median follow-up of 6.7 months (range, 2-11). Four patients (25%) had ECOG PS 1 and had received two prior regimens. No grades 3 or 4 treatment-related adverse events (TRAEs) occurred within the first two cycles. The most common grades 1 and 2 TRAEs were fatigue (7, 43.8%), diarrhea (5, 31.3%), and dysphonia (5, 31.3%). Objective responses were seen in six patients (37.5%; 95% confidence interval, 15.2-64.6), including two complete responses (12.5%). One additional patient with bone-only disease obtained a decrease in FDG uptake and in circulating tumor DNA consistent with response. Angiogenesis-related gene alterations were found in 57% responders versus 0% nonresponders. Conclusion: The durvalumab and cabozantinib combination was safe and endowed with preliminary clinical activity in patients with advanced UC. Mature results will clarify the role of cabozantinib and that of tumor biomarkers in this tumor type.