EV-201 study: 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

TPS542 Background: The majority of patients with locally advanced or metastatic urothelial cancer (la/mUC) will not respond to immune checkpoint inhibitors (CPIs) given in the post-platinum or cisplatin ineligible setting, and there are currently no approved standard therapies after disease progression. Enfortumab vedotin (EV), an antibody-drug conjugate, delivers the microtubule-disrupting agent monomethyl auristatin E to tumors expressing Nectin-4, which is overexpressed in mUC. Preliminary results from an ongoing phase 1 study of EV monotherapy in pts with mUC (Petrylak ASCO 2017) showed that EV was well tolerated in pts with mUC. Nausea (36%), pruritus (31%), and fatigue (30%) were the most commonly reported treatment-related AEs. The most common grade ≥3 AEs (regardless of attribution) were urinary tract infection (11%) and hypophosphatemia (9%). EV showed an objective response rate (ORR) of 41% (29 out of 71 pts) across all dose levels and 53% (16 out of 30 pts) ORR at the recommended phase 2 dose of 1.25 mg/kg. The ORR was not diminished in pts with prior CPI use (44%), prior taxane use (41%) or in pts with liver metastases (47%). These encouraging results along with a favorable safety and tolerability profile warrant further investigation of EV as a monotherapy. Methods: This single-arm, open label, multicenter phase 2 study (NCT03219333) evaluates the antitumor activity and safety of EV monotherapy in ~120 pts with la/mUC. Pts must have previously received a CPI and either have received prior platinum or be ineligible for cisplatin. Pts must have histologically or cytologically documented transitional cell carcinoma of the urothelium that progressed during or following receipt of most recent therapy. The primary objective is to determine antitumor activity of EV as measured by ORR. Secondary objectives include assessment of duration of response, disease control rate, PFS, OS, and safety/tolerability of EV. Pts must have tumor tissue available for exploratory analyses. Response is assessed per RECIST v1.1. Study enrollment began in Sept 2017. Clinical trial information: NCT03219333.