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

Abstract 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. Methods : Patients with an ECOG performance status 0-1, UC and non-UC histology, failure of a maximum of 2 regimens received cabozantinib 40 mg daily, orally, in combination with durvalumab 1500 mg, intravenously, every 28 days. Response was evaluated by RECIST criteria v.1.1 every 2 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 (25%) had an ECOG PS 1 and the same had received 2 prior regimens. No Grade 3-4 treatment-related adverse events (TRAEs) occurred within the first 2 cycles. The most common Grade 1-2 TRAEs were fatigue (7, 43.8%), diarrhea (5, 31.3%), dysphonia (5, 31.3%). Objective responses were seen in 6 patients (37.5%, 95% confidence interval 15.2-64.6), including 2 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 vs 0% nonresponders. Conclusions : 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. Microabstract : We have reported the preliminary safety and activity results of the combination of an immunotherapeutic agent, durvalumab, with a drug endowed with antiangiogenic activity, cabozantinib. The combination therapy was safe and demonstrated preliminary activity in the first patients enrolled, while the study is still recruiting patients, pending confirmation with a larger sample size and longer follow-up duration.