EV-201: A single-arm, open-label, multicenter study of enfortumab vedotin for treatment of patients with locally advanced or metastatic urothelial cancer who previously received immune checkpoint inhibitor therapy

Abstract

Background: Most patients (pts) with locally advanced or metastatic urothelial cancer (la/mUC) will not respond to immune checkpoint inhibitors (CPIs) in the post-platinum or first-line cisplatin ineligible setting. Enfortumab vedotin (EV), an antibodydrug conjugate, delivers the microtubule-disrupting agent monomethyl auristatin E to tumors expressing Nectin-4, which is highly expressed in 97% of mUC pt samples (Petrylak ASCO 2017). In a phase 1 study (NCT02091999), EV monotherapy was generally well tolerated at the recommended dose of 1.25 mg/kg. In this study, 29% of mUC pts had liver metastasis, and most had prior treatment with a CPI (79%), platinum (94%), and/or taxanes (29%). Interim results in mUC pts treated at 1.25 mg/kg showed a confirmed objective response rate (ORR) of 41% (46 of 112) and an ORR of 40% in pts previously treated with a CPI (36 of 89). The most common treatmentrelated adverse events (AEs) among pts with mUC were fatigue (54%), alopecia (45%), and decreased appetite (40%). There were no treatment-related Grade >=3AE in>=5% of mUC pts. Four possibly treatmentrelated fatal AEs were reported: respiratory failure, urinary tract obstruction, diabetic ketoacidosis, and multiorgan failure. These encouraging results along with a favorable safety and tolerability profile warrant further investigation of EV as a monotherapy. Trial design: This single-arm, open-label, multicenter phase 2 study (NCT03219333) evaluates the antitumor activity and safety of EV monotherapy in la/mUC pts with prior CPI treatment. The study will enroll~100 platinum-treated pts (Cohort 1) and ~100 platinum-naive and cisplatin-ineligible pts (Cohort 2). The primary objective is to determine antitumor activity of EV as measured by ORR assessed per RECIST v1.1. Secondary objectives include assessment of duration of response, disease control rate, PFS, OS, safety, and tolerability. Pts must have tumor tissue available for exploratory analyses. Study enrollment began in Sep 2017.