A Randomized Phase 3 Study Evaluating Cystectomy With Perioperative Pembrolizumab and Cystectomy With Perioperative Enfortumab Vedotin and Pembrolizumab Versus Cystectomy Alone in Participants Who Are Cisplatin-Ineligible or Decline Cisplatin With Muscle-Invasive Bladder Cancer (KEYNOTE-905/EV-303)
A Randomized Phase 3 Study Evaluating Cystectomy With Perioperative Pembrolizumab and Cystectomy With Perioperative Enfortumab Vedotin and Pembrolizumab Versus Cystectomy Alone in Participants Who Are Cisplatin-Ineligible or Decline Cisplatin With Muscle-Invasive Bladder Cancer (KEYNOTE-905/EV-303)
This is a study of perioperative pembrolizumab or enfortumab vedotin in combination with pembrolizumab in participants who are cisplatin-ineligible or decline cisplatin with muscle-invasive bladder cancer (MIBC).
The primary hypothesis is that perioperative pembrolizumab plus radical cystectomy (RC) plus pelvic lymph node dissection (PLND) and perioperative enfortumab vedotin in combination with pembrolizumab plus RC+PLND will achieve superior event-free survival (EFS) compared with RC+PLND alone.
With Amendment 5, outcome measures for programmed cell death ligand 1 (PD-L1) combined positive score (CPS) were removed.
With Amendment 8, the primary outcome measure of pathologic complete response (pCR) rates was changed to a secondary outcome measure.
Inclusion Criteria:
Have a histologically confirmed diagnosis of urothelial carcinoma/muscle-invasive bladder cancer [MIBC] (cT2-T4aN0M0 or T1-T4aN1M0) with predominant (≥50%) urothelial histology to be confirmed by Blinded Independent Central Review (BICR) (central pathology and/or imaging).
Clinically nonmetastatic bladder cancer determined by imaging
Eligible for radical cystectomy (RC) + pelvic lymph node dissection (PLND), and agreement to undergo curative intent standard RC + PLND (including prostatectomy if applicable)
Ineligible for treatment with cisplatin, as defined by meeting at least one of the following criteria OR be eligible for treatment with cisplatin but decline treatment with cisplatin-based chemotherapy:
Transurethral resection (TUR) of a bladder tumor that is submitted for central pathology assessment and adequate to determine urothelial histology and PD-L1 expression assessment
ECOG performance status of 0, 1, or 2
Adequate organ function
A male participant is eligible to participate if he agrees to use contraception and refrain from donating sperm during the intervention period and for at least 180 days after the last dose of enfortumab vedotin. If the male participants are receiving pembrolizumab only or undergoing surgery only, there are no contraception requirements
A female participant is eligible to participate if she is not pregnant, not breastfeeding, and at least 1 of the following conditions applies: Not a (woman of childbearing potential) WOCBP or a WOCBP who agrees to use a highly effective contraceptive method or be abstinent from heterosexual intercourse (as their preferred and usual lifestyle) during the intervention period and for at least 120 days after the last dose of pembrolizumab and at least 180 days after the last dose of enfortumab vedotin; whichever comes last. A female participant must agree not to donate eggs during this period as well
A WOCBP must have a negative highly sensitive pregnancy test within 24 hours before the first dose of study intervention
Exclusion Criteria:
Mobile, Alabama 36604, United States
Washington D.C., District of Columbia 20007, United States
Indianapolis, Indiana 46202, United States
Albuquerque, New Mexico 87106, United States
Tulsa, Oklahoma 74146, United States
Philadelphia, Pennsylvania 19104, United States
Buenos Aires, Buenos Aires F.D. C1419AHN, Argentina
St-Lambrechts-Woluwe, Bruxelles-Capitale, Region de 1200, Belgium
Montreal, Quebec H1T 2M4, Canada
Bogotá, Bogota D.C. 111321, Colombia
Cali, Valle del Cauca Department 760032, Colombia
Tübingen, Baden-Wurttemberg 72076, Germany
Roma, Abruzzo 00168, Italy
Orbassano, Piedmont 10043, Italy
Terni, 05100, Italy
Tomitake, Nagano 381-8551, Japan
Ina-machi, Saitama 362-0806, Japan
Bunkyō, Tokyo 113-8519, Japan
Minato-ku, Tokyo 105-8470, Japan
Toyoma, Toyama 930-0194, Japan
Lembah Pantai, Kuala Lumpur 59100, Malaysia
Monterrey, Nuevo León 66269, Mexico
Aguascalientes, 20010, Mexico
Bydgoszcz, Kuyavian-Pomeranian Voivodeship 85-796, Poland
Wroclaw, Lower Silesian Voivodeship 50-556, Poland
Słupsk, Pomeranian Voivodeship 76-200, Poland
Bielsko-Biala, Silesian Voivodeship 43-300, Poland
Ufa, Baskortostan, Respublika 450081, Russia
Krasnoyarsk, Krasnoyarsk Krai 660133, Russia
Moscow, Moscow 115478, Russia
Nizhny Novgorod, Nizhny Novgorod Oblast 603074, Russia
Saint Petersburg, Sankt-Peterburg 197022, Russia
Saint Petersburg, Sankt-Peterburg 197758, Russia
Saratov, Saratov Oblast 410012, Russia
Songpagu, Seoul 05505, South Korea
Deagu, Taegu-Kwangyokshi 41404, South Korea
Pozuelo de Alarcón, Madrid, Comunidad de 28223, Spain
Istanbul, 34722, Turkey (Türkiye)
Istanbul, 34899, Turkey (Türkiye)
Konya, 42080, Turkey (Türkiye)
Trabzon, 61080, Turkey (Türkiye)
Cherkasy, Cherkasy Oblast 18009, Ukraine
Dnipro, Dnipropetrovsk Oblast 49102, Ukraine
Dnipropetrovsk, Dnipropetrovsk Oblast 49005, Ukraine
Kharkiv, Kharkiv Oblast 61037, Ukraine
Kharkiv, Kharkiv Oblast 61166, Ukraine
Kherson, Kherson Oblast 73034, Ukraine
Lviv, Lviv Oblast 79010, Ukraine
London, Hammersmith and Fulham W6 8RF, United Kingdom
London, London, City of EC1A 7BE, United Kingdom