Abstract B26: EV-301: A phase 3 study evaluating enfortumab vedotin versus chemotherapy in patients with locally advanced or metastatic urothelial cancer (la/mUC) who have progressed on platinum-containing chemotherapy or anti-PD-(L)1 therapy
Authors: Petrylak Daniel , Rosenberg Jonathan , Duran Ignacio , Loriot Yohann , Sonpavde Guru , Wu Chunzhang , Gartner Elaina , Bertrandt Amal Melhem- , Powles Thomas 
Published: August 2020

Abstract
Background: Currently, there are no FDA-approved therapies for patients (pts) with la/mUC who have failed treatment with chemotherapy and immune checkpoint inhibitors, such as antibodies targeting PD-1 or PD-L1. Survival benefits with anti-PD-(L)1 therapy have not been consistently observed and objective response rates (ORR) in the second-line setting are ≤21%. Moreover, there are limited data on response to chemotherapy in pts who progressed on immune checkpoint inhibitors. Enfortumab vedotin (EV) is a fully humanized monoclonal antibody that delivers the microtubule-disrupting agent, monomethyl auristatin E, to tumors expressing Nectin-4. Nectin-4 has limited expression in normal tissue but is highly expressed in cancer cells, particularly UC. In a phase 1 study (EV-101; NCT02091999), EV 1.25 mg/kg was generally well tolerated and demonstrated a confirmed ORR of 43% with a duration of response (DoR) of 7.4 mo. Median overall survival (OS) was 12.3 mo and OS rate at 1 yr was 51.8%. Similar results were observed in a number of study subpopulations, including pts with prior anti-PD-(L)1 treatment and liver metastases at baseline. A pivotal phase 2 study of EV in pts with la/mUC with prior immune checkpoint inhibitor treatment (EV-201; NCT03219333) is ongoing, with enrollment into a cohort of pts with la/mUC previously treated with platinum and immune checkpoint inhibitor therapies now completed.
Trial Design: EV-301 is a global, multicenter, open-label phase 3 trial (NCT03474107) enrolling ~550 adult pts with la/mUC with an ECOG score ≤1, who have received a prior platinum-containing chemotherapy and have experienced disease progression during or following treatment with anti-PD-(L)1 therapy. Patients will be randomized 1:1 to receive EV (1.25 mg/kg) administered IV on Days 1, 8, and 15 of each 28-day cycle (Arm A), or investigator choice of IV docetaxel, paclitaxel, or vinflunine (EU only) on Day 1 of each 21-day cycle (Arm B). Treatment with the study drug will continue until radiologic disease progression assessment, intolerance, or other discontinuation criterion is met. Radiologic assessments of tumor response status will be performed at baseline and every 8 weeks. The primary endpoint of EV-301 is to compare the OS of pts treated with EV with the OS of pts treated with chemotherapy alone; secondary endpoints include EV safety/tolerability profile, ORR, progression-free survival, DoR, and disease control rate assessment using RECIST v.1.1 criteria. Quality-of-life parameters and patient-reported outcomes will also be assessed using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire and EuroQoL 5-dimension 5-Level Questionnaire.
Citation Format: Daniel Petrylak, Jonathan Rosenberg, Ignacio Duran, Yohann Loriot, Guru Sonpavde, Chunzhang Wu, Elaina Gartner, Amal Melhem- Bertrandt, Thomas Powles. EV-301: A phase 3 study evaluating enfortumab vedotin versus chemotherapy in patients with locally advanced or metastatic urothelial cancer (la/mUC) who have progressed on platinum-containing chemotherapy or anti-PD-(L)1 therapy [abstract]. In: Proceedings of the AACR Special Conference on Bladder Cancer: Transforming the Field; 2019 May 18-21; Denver, CO. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(15_Suppl):Abstract nr B26.