Bladder Cancer Clinical Trial
Perioperative Pembrolizumab (MK-3475) Plus Cystectomy or Perioperative Pembrolizumab Plus Enfortumab Vedotin Plus Cystectomy Versus Cystectomy Alone in Participants Who Are Cisplatin-ineligible or Decline Cisplatin With Muscle-invasive Bladder Cancer (MK-3475-905/KEYNOTE-905/EV-303)
Summary
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 pathologic complete response (pCR) rates (based on central pathologic review) and 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.
Eligibility Criteria
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:
Impaired renal function with measured or calculated creatinine clearance (CrCl) 30 to 59 mL/min (calculated by Cockcroft-Gault method, Modification of Diet of Renal Disease [MDRD] equations, or measured by 24-hour urine collection)
Eastern Cooperative Oncology Group (ECOG) Performance Status 2
Common Terminology Criteria for Adverse Events (CTCAE) v.4 Grade ≥2 audiometric hearing loss
New York Heart Association (NYHA) Class III heart failure
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:
Known additional nonurothelial malignancy that is progressing or has required active anticancer treatment ≤3 years of study randomization, with certain exceptions
Has ≥ N2 or metastatic disease (M1) as identified by imaging
Received any prior systemic treatment, chemoradiation, and/or radiation therapy for for muscle-invasive bladder cancer (MIBC) or non-muscle invasive bladder cancer (NMIBC)
Received prior therapy with an anti-programmed cell death protein 1 (PD-1), anti-programmed death-ligand 1 (PD-L1), or anti-programmed cell death 1 ligand 2 (PD-L2), or with an agent directed to another stimulatory or coinhibitory T-cell receptor
Received prior systemic anticancer therapy including investigational agents within 3 years prior to randomization
Received any prior radiotherapy to the bladder
Received a partial cystectomy of the bladder to remove any non-muscle-invasive bladder cancer (NMIBC) or MIBC
Received a live or live-attenuated vaccine within 30 days before the first dose of study intervention
Current participation in or participation in a study of an investigational agent or use of an investigational device within 4 weeks prior to the first dose of study intervention
Ongoing sensory or motor neuropathy Grade 2 or higher
Diagnosis of immunodeficiency or receipt of chronic systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior the first dose of study drug. Physiologic replacement doses of corticosteroids are permitted for participants with adrenal insufficiency.
Hypersensitivity to monoclonal antibodies (including pembrolizumab) and/or any of their excipients
Severe hypersensitivity (≥ Grade 3) to enfortumab vedotin or any excipient contained in the drug formulation of enfortumab vedotin
Active keratitis or corneal ulcerations. Participants with superficial punctate keratitis are allowed if the disorder is being adequately treated in the opinion of the investigator
Active autoimmune disease that has required systemic therapy in past 2 years (i.e., with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic therapy and is allowed
Has uncontrolled diabetes
History of (noninfectious) pneumonitis that required steroids, or current pneumonitis
Active infection requiring systemic therapy
Has had an allogeneic tissue/solid organ transplant
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There are 235 Locations for this study
Mobile Alabama, 36604, United States
Little Rock Arkansas, 72205, United States
Fullerton California, 92835, United States
La Jolla California, 92037, United States
Santa Monica California, 90404, United States
Aurora Colorado, 80045, United States
Washington District of Columbia, 20007, United States More Info
Atlanta Georgia, 30322, United States
Chicago Illinois, 60612, United States More Info
Chicago Illinois, 60637, United States
Indianapolis Indiana, 46202, United States More Info
Wichita Kansas, 67226, United States
New Orleans Louisiana, 70112, United States
Scarborough Maine, 04074, United States
Baltimore Maryland, 21204, United States
Burnsville Minnesota, 55337, United States
Morristown New Jersey, 07960, United States
Albuquerque New Mexico, 87106, United States
Lake Success New York, 11042, United States
New York New York, 10016, United States
New York New York, 10029, United States More Info
Tulsa Oklahoma, 74146, United States
Portland Oregon, 97213, United States
Bala-Cynwyd Pennsylvania, 19004, United States
Philadelphia Pennsylvania, 19104, United States
Philadelphia Pennsylvania, 19107, United States
Philadelphia Pennsylvania, 19111, United States
Pittsburgh Pennsylvania, 15212, United States
Greenville South Carolina, 29607, United States
Myrtle Beach South Carolina, 29572, United States More Info
Nashville Tennessee, 37232, United States
Dallas Texas, 75246, United States
Charleston West Virginia, 25304, United States
Buenos Aires , C1419, Argentina More Info
Blacktown New South Wales, 2148, Australia
Macquarie Park New South Wales, 2109, Australia
Cairns Queensland, 4870, Australia
South Brisbane Queensland, 4101, Australia
Box Hill Victoria, 3128, Australia
Clayton Victoria, 3168, Australia
Bruxelles Bruxelles-Capitale, Region De, 1200, Belgium More Info
Yvoir Namur, 5530, Belgium
Leuven Vlaams-Brabant, 3000, Belgium
Vancouver British Columbia, V5Z 4, Canada More Info
Victoria British Columbia, V8T 2, Canada
Moncton New Brunswick, E1C 6, Canada More Info
Toronto Ontario, M5G 2, Canada
Montreal Quebec, H1T 2, Canada
Medellin Antioquia, 05003, Colombia More Info
Dijon Cote-d Or, 21000, France
Besancon Doubs, 25000, France
Bordeaux Gironde, 33075, France
Toulouse Haute-Garonne, 31059, France
Rennes Ille-et-Vilaine, 35033, France
Montpellier Languedoc-Roussillon, 34295, France More Info
Pierre Benite Rhone, 69310, France
Villejuif Val-de-Marne, 94805, France
Paris , 75014, France
Paris , 75015, France
Tuebingen Baden-Wurttemberg, 72076, Germany More Info
Muenchen Bayern, 81377, Germany More Info
Magdeburg Sachsen-Anhalt, 39120, Germany More Info
Dresden Sachsen, 01307, Germany
Gera Thuringen, 07548, Germany More Info
Hamburg , 20246, Germany More Info
Gyor , 9023, Hungary
Kaposvar , 7400, Hungary
Afula , 18341, Israel
Orbassano Piemonte, 10043, Italy More Info
Vicenza Veneto, 36100, Italy
Catania , 95123, Italy More Info
Pavia , 27100, Italy
Terni , 05100, Italy More Info
Koshigaya Saitama, 343-8, Japan More Info
Seongnam-si Kyonggi-do, 13620, Korea, Republic of More Info
Songpagu Seoul, 05505, Korea, Republic of
Deagu Taegu-Kwangyokshi, 41404, Korea, Republic of More Info
Monterrey Nuevo Leon, 66269, Mexico
Aguascalientes , 20010, Mexico
Chihuahua , 31000, Mexico
Ciudad de Mexico , 14080, Mexico
Metepec , 52140, Mexico
Mexico City , 06700, Mexico
Quezon City National Capital Region, 1112, Philippines More Info
Wroclaw Dolnoslaskie, 50-55, Poland More Info
Bydgoszcz Kujawsko-pomorskie, 85-79, Poland More Info
Otwock Mazowieckie, 05-40, Poland
Bialystok Podlaskie, 15-02, Poland
Slupsk Pomorskie, 76-20, Poland More Info
Bielsko-Biala Slaskie, 43-30, Poland
Ufa Baskortostan, Respublika, 45008, Russian Federation
Ivanovo Ivanovskaya Oblast, 15304, Russian Federation
Krasnoyarsk Krasnoyarskiy Kray, 66013, Russian Federation
Kursk Kurskaya Oblast, 30552, Russian Federation
Moscow Moskva, 11547, Russian Federation
Moscow Moskva, 11999, Russian Federation
Moscow Moskva, 12135, Russian Federation
Murmansk Murmanskaya Oblast, 18305, Russian Federation
Nizhny Novgorod Nizhegorodskaya Oblast, 60307, Russian Federation
Omsk Omskaya Oblast, 64401, Russian Federation
Saint Petersburg Sankt-Peterburg, 18866, Russian Federation
Saint-Petersburg Sankt-Peterburg, 19702, Russian Federation
Saint-Petersburg Sankt-Peterburg, 19775, Russian Federation
St. Petersburg Sankt-Peterburg, 19404, Russian Federation
Saratov Saratovskaya Oblast, 41001, Russian Federation
Ekaterinburg Sverdlovskaya Oblast, 62003, Russian Federation
Tyumen Tyumenskaya Oblast, 62500, Russian Federation
Singapore Central Singapore, 11907, Singapore
Pretoria Gauteng, 0001, South Africa More Info
Badalona Barcelona, 08916, Spain More Info
Pozuelo de Alarcon Madrid, Comunidad De, 28223, Spain
Valencia Valenciana, Comunitat, 46009, Spain More Info
Stockholm Stockholms Lan, 171 7, Sweden More Info
Umea Vasterbottens Lan, 901 8, Sweden
Bangkok Krung Thep Maha Nakhon, 10700, Thailand More Info
Istanbul , 34722, Turkey More Info
Istanbul , 34899, Turkey More Info
Konya , 42080, Turkey More Info
Trabzon , 61080, Turkey More Info
Cherkasy Cherkaska Oblast, 18009, Ukraine
Dnipropetrovsk Dnipropetrovska Oblast, 49005, Ukraine
Dnipro Dnipropetrovska Oblast, 49102, Ukraine
Kharkiv Kharkivska Oblast, 61000, Ukraine More Info
Kharkiv Kharkivska Oblast, 61037, Ukraine
Kharkiv Kharkivska Oblast, 61166, Ukraine
Antonivka Village Khersonska Oblast, 73000, Ukraine
Kyiv Kyivska Oblast, 03022, Ukraine
Lviv Lvivska Oblast, 79010, Ukraine
Lviv Lvivska Oblast, 79031, Ukraine
Zhytomyr Zhytomyrska Oblast, 10002, Ukraine
Kyiv , 03115, Ukraine
Canterbury England, CT1 3, United Kingdom
Middlesbrough England, TS4 3, United Kingdom More Info
Stevenage Hertfordshire, SG1 4, United Kingdom
London London, City Of, EC1A , United Kingdom More Info
London London, City Of, SW3 6, United Kingdom More Info
London London, City Of, W6 8R, United Kingdom More Info
West Midlands Walsall, WS2 9, United Kingdom
Truro , TR1 3, United Kingdom
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