223TiP - EV-301: A phase III trial in progress evaluating enfortumab vedotin versus chemotherapy in patients with locally advanced or metastatic urothelial carcinoma

Background

Locally advanced or metastatic urothelial carcinoma (la/mUC) is an aggressive cancer with low survival rates. Anti-PD-(L)1 antibodies are current treatment options for patients who progressed during or after platinum-based chemotherapy. While some of these patients achieve durable responses with anti-PD-(L)1 therapy, response rates are ≤21%; as such, novel therapies are needed for patients after treatment with platinum and anti-PD-(L)1 therapies. Enfortumab vedotin (EV) is an investigational humanized monoclonal antibody that delivers the microtubule-disrupting agent monomethyl auristatin E to tumors expressing Nectin-4, which is highly expressed in la/mUC. In a multicohort phase 2 study of EV (EV-201; NCT03219333), which included sites in Japan and Korea, single-agent EV 1.25 mg/kg was generally well tolerated. In Cohort 1 of EV-201 (closed to enrollment), EV demonstrated a confirmed ORR of 44% and a median DoR of 7.6 months as assessed by independent central review in patients with la/mUC with prior platinum chemotherapy and antiPD(L)1.

Trial design

EV-301 (NCT03474107) is a global, multicenter, open-label, phase 3 trial being conducted in the USA, Europe, and Asia, including sites in Japan, Korea, and Taiwan. Adult patients with la/mUC and 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 are eligible; these patients are consistent with the population in Cohort 1 of EV-201. Approximately 550 patients will be randomized (1:1) to receive EV (1.25 mg/kg) by IV on Days 1, 8, and 15 of each 28-day cycle (Arm A), or investigator’s choice of IV docetaxel, paclitaxel, or vinflunine (where approved) on Day 1 of each 21day cycle (Arm B). Treatment with EV will continue until radiological disease progression, intolerance, or other discontinuation criterion is met. Radiological assessments of tumor response status will be performed at baseline and every 8 weeks. The primary endpoint is overall survival; secondary endpoints include PFS, DoR, ORR, and assessment of safety/tolerability and quality-of-life parameters.

Clinical trial identification

NCT03474107.

Legal entity responsible for the study

Astellas Pharma US, Inc.

Funding

Astellas Pharma US, Inc.

Disclosure

D.P. Petrylak: Research grant / Funding (institution): Astellas ; Advisory / Consultancy, Research grant / Funding (institution): AstraZeneca; Advisory / Consultancy, Research grant / Funding (institution): Bayer; Advisory / Consultancy, Research grant / Funding (institution), Shareholder / Stockholder / Stock options: Bellicum; Advisory / Consultancy, Research grant / Funding (institution): Dendreon; Advisory / Consultancy: Exelixis; Advisory / Consultancy: Ferring; Advisory / Consultancy, Research grant / Funding (institution): Johnson and Johnson; Advisory / Consultancy, Research grant / Funding (institution): Lilly; Advisory / Consultancy, Research grant / Funding (institution): Medivation; Advisory / Consultancy, Research grant / Funding (institution): Millineum; Advisory / Consultancy, Research grant / Funding (institution): Pfizer; Advisory / Consultancy, Research grant / Funding (institution): Roche Laboratories; Advisory / Consultancy, Research grant / Funding (institution): Sanofi Aventis; Research grant / Funding (institution): Agensys; Research grant / Funding (institution): Clovis; Shareholder / Stockholder / Stock options: Tyme; Research grant / Funding (institution): Eli Lilly; Research grant / Funding (institution): Endocyte; Research grant / Funding (institution): Genentech; Research grant / Funding (institution): Innocrin. J.E. Rosenberg: Advisory / Consultancy, Research grant / Funding (institution): Astellas; Advisory / Consultancy, Research grant / Funding (institution): Roche; Advisory / Consultancy, Research grant / Funding (institution): Seattle Genetics; Advisory / Consultancy: Merck; Advisory / Consultancy: BMS; Advisory / Consultancy, Research grant / Funding (institution): AstraZeneca; Travel / Accommodation / Expenses: Bayer; Advisory / Consultancy: Lilly; Advisory / Consultancy: Sanofi; Advisory / Consultancy: EMD Serono. J. Lee: Advisory / Consultancy, Research grant / Funding (institution): Pfizer Korea; Advisory / Consultancy, Research grant / Funding (institution): Ipsen Korea; Advisory / Consultancy: Janssen; Advisory / Consultancy: Sanofi Aventis; Advisory / Consultancy: Novartis Korea; Advisory / Consultancy: Astellas Korea; Advisory / Consultancy: BMS Korea. I. Duran: Advisory / Consultancy: Seattle Genetics. Y. Loriot: Advisory / Consultancy: Astellas; Advisory / Consultancy: Seattle Genetics; Advisory / Consultancy, Research grant / Funding (institution): Janssen; Advisory / Consultancy, Research grant / Funding (institution): Sanofi; Advisory / Consultancy, Research grant / Funding (institution): MSD; Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: Roche. G. Sonpavde: Research grant / Funding (institution): Boehringer Ingelheim; Research grant / Funding (institution): Bayer; Research grant / Funding (institution): Onyx-Amgen; Advisory / Consultancy, Research grant / Funding (institution): Pfizer; Advisory / Consultancy: Genentech; Advisory / Consultancy: Novartis; Advisory / Consultancy: Argos; Advisory / Consultancy, Research grant / Funding (institution): Merck; Advisory / Consultancy: Sanofi; Advisory / Consultancy: Agensys; Advisory / Consultancy: Astellas; Speaker Bureau / Expert testimony: Clinical Care Options; Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: Uptodate; Advisory / Consultancy: Biotheranostics; Advisory / Consultancy: Exelixis; Advisory / Consultancy: Bristol-Myers-Squibb; Advisory / Consultancy: Janssen; Advisory / Consultancy: Amgen; Advisory / Consultancy: Eisai; Advisory / Consultancy: NCCN. C. Wu: Full / Part-time employment: Astellas. E.M. Gartner: Full / Part-time employment: Seattle Genetics, Inc. A. Melhem-Bertrandt: Full / Part-time employment: Astellas. T. Powles: Honoraria (self), Research grant / Funding (institution): AstraZeneca; Honoraria (self), Research grant / Funding (institution): Roche; Honoraria (self): Pfizer; Honoraria (self): Novartis; Honoraria (self): Merck; Honoraria (self): BMS. All other authors have declared no conflicts of interest.