2709 - EV-301: An Open-Label, Randomized Phase 3 Study to Evaluate Enfortumab Vedotin Versus Chemotherapy in Patients With Previously Treated Locally Advanced or Metastatic Urothelial Cancer (la/mUC)

Background

Standard first-line treatment for patients (pts) with la/mUC is cisplatin-based chemotherapy or carboplatin-based chemotherapy for pts unfit for cisplatin. Recently, immune checkpoint inhibitors (CPIs) have become standard treatment options for pts who progressed during/after platinum-based chemotherapy or are ineligible for cisplatin. While some pts with la/mUC achieve durable responses with CPIs, only a minority respond. Following failure with CPI, no therapies are approved. Enfortumab vedotin (EV) is a fully humanized monoclonal antibody that delivers the microtubule-disrupting agent monomethyl auristatin E to tumors expressing Nectin-4, which is highly expressed in 97% of mUC patient samples (Petrylak ASCO 2017). In a phase 1 study (EV-101; NCT02091999), single-agent EV at the established recommended phase 2 dose of 1.25 mg/kg was generally well tolerated and demonstrated a confirmed objective response rate of 41% (n = 46/112) across the overall population of pts with mUC; in pts with prior CPI therapy, a confirmed ORR of 40% (n = 36/89) was observed.

Trial design

EV-301 is a global, multicenter, open-label phase 3 trial (NCT03474107) enrolling adult pts with la/mUC and an ECOG score ≤1, who have received one prior platinum-containing chemotherapy, and have experienced disease progression during or following treatment with a CPI. Approximately 550 pts will be randomized 1:1 to receive EV 1.25 mg/kg (Arm A) or chemotherapy (Arm B); randomization will be stratified by ECOG score, regions of the world, and liver metastases at baseline. Patients in Arm A will receive EV on Days 1, 8, and 15 of each 28-day cycle; pts in Arm B will receive either docetaxel, paclitaxel, or vinflunine (determined by investigator) on Day 1 of every 21-day cycle. Patients will continue to receive study treatment until disease progression, intolerance, or other discontinuation criterion is met. The primary endpoint is overall survival; secondary endpoints include progression-free survival, duration of response, and overall response rate, as well as assessment of safety/tolerability, and quality-of-life parameters.

Clinical trial identification

NCT03474107.

Legal entity responsible for the study

Astellas Pharma, Inc.

Funding

Astellas Pharma, Inc.

Editorial Acknowledgement

Medical writing and editorial support was provided by Regina Switzer, PhD (SuccinctChoice Medical Communications, Chicago, IL).

Disclosure

D.P. Petrylak: Grants, personal fees, or other support: Astellas, AstraZeneca, Bayer, Bellicum, Dendreon, Exelixis, Ferring, Johnson & Johnson, Lilly Medivation, Millenium, Pfizer, Roche Laboratories, Sanofi Aventis, Agensys, Clovis, Eli Lilly, Endocyte, Genentech, Innocrin, Lilly, Medimmune, Medivation, Merck, Novartis, Sanofi Aventis, Sotio, Bellicum, Tyme. J. Rosenberg: Grants or personal fees: Astellas, Roche, Seattle Genetics, Merck, BMS, AstraZeneca, Bayer, Lilly, Sanofi, EMD Serono. I. Duran: Personal fees: Seattle Genetics, outside the submitted work. Y. Loriot: Personal fees: Astellas, Seattle Genetics, during the conduct of the study; Grants and personal fees: Janssen, Sanofi, MSD, AstraZeneca, Roche, outside the submitted work. G. Sonpavde: Grants or personal fees: Boehringer-Ingelheim, Bayer, Onyx-Amgen, Celgene, Pfizer, Merck, Genentech, Novartis, Argos, Sanofi, Agensys/Astellas, Clinical Care Options, AstraZeneca, Uptodate, Biotheranostics, Exelixis, Bristol-Myers-Squibb, Janssen, Amgen, Eisai, NCCN, Physicians Education Resource, Onclive, Research to Practice, QUILT/Oncotherapeutics symposium, EMD Serono. C. Wu, A. Melhem-Bertrandt: Employee of Astellas. E. Gartner: Employee of Seattle Genetics. T. Powles: Personal fees or grants: AstraZeneca, Roche, Pfizer, Novartis, Merck, BMS.