EV-103 dose escalation/cohort A: 5-year follow-up of enfortumab vedotin plus pembrolizumab in previously untreated locally advanced/metastatic urothelial carcinoma

<h3>Background</h3> Dose escalation/cohort A of the phase Ib/II EV-103/KEYNOTE-869 study (NCT03288545) assessed safety and efficacy of enfortumab vedotin (EV) plus pembrolizumab (P) in cisplatin-ineligible patients with previously untreated locally advanced/metastatic urothelial carcinoma (la/mUC). Here we report updated results after 5 years of follow-up. <h3>Methods</h3> Patients received EV 1.25 mg/kg intravenously on days 1 and 8, and pembrolizumab 200 mg on day 1 of every 3-week cycle. The primary endpoint was safety. Select secondary endpoints included objective response rate (ORR), duration of response (DOR), progression-free survival (PFS), and overall survival (OS). <h3>Results</h3> Forty-five patients were enrolled. Baseline characteristics were representative of a cisplatin-ineligible population; 84.4% had visceral disease and 55.6% had reduced renal function (creatine clearance <60 ml/min). The median follow-up time was 62.1 months [95% confidence interval (CI) 59.4-63.1]. There were no new safety signals, and safety was consistent with EV+P in other la/mUC studies. Confirmed ORR was 73.3%, median DOR was 22.1 months [95% CI 8.4-not estimable (NE)], median PFS was 12.7 months (95% CI 6.1-NE), and median OS was 26.1 months (95% CI 15.5-NE). The estimated 5-year survival rate was 41.5% (95% CI 26.5-56.0). <h3>Conclusion</h3> Along with results from EV-302/KEYNOTE-A39 (NCT04223856), the 5-year results further support the sustained benefit from EV+P and establish the combination as the standard of care for previously untreated la/mUC.