Efficacy and Safety of Pembrolizumab (MK-3475) in Combination With Bacillus Calmette-Guerin (BCG) in High-Risk Non-Muscle Invasive Bladder Cancer (HR NMIBC) (MK-3475-676/KEYNOTE-676)
Pembrolizumab: Pembrolizumab IV infusion of 200 mg Q3W for BCG Post-Induction Cohort (Cohort A), or IV infusion of 400 mg Q6W for BCG Naïve Cohort (Cohort B), according to randomization
BCG: BCG (intravesical instillation): powder for instillation fluid for intravesical use, administered during Induction and Maintenance therapy
Study summary
Researchers are looking for new ways to treat high-risk non muscle invasive bladder cancer (HR NMIBC). NMIBC is cancer in the tissue that lines the inside of the bladder but has not spread to the bladder muscle or outside of the bladder. High-risk means NMIBC may have a high chance of getting worse or coming back after treatment.
The goals of this study are to learn: 1. If more people who receive pembrolizumab with Bacillus Calmette-Guerin (BCG) have no signs of cancer in their body and live longer without the cancer growing, spreading, or coming back compared to people who receive BCG alone. 2. About the safety and how well people tolerate BCG alone or in combination with pembrolizumab.
Eligibility
Sex
ALL
Min age
18 Years
Max age
—
Healthy volunteers
No
Inclusion Criteria:
* Have locally and blinded independent central review (BICR)-confirmed histological diagnosis of high-risk non-muscle invasive (T1, high grade Ta and/or CIS) UC of the bladder
* Has undergone cystoscopy/ transurethral resection of bladder tumor (TURBT) to remove all resectable disease
* Has provided tissue for biomarker analysis
* Has Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2
* Has adequate organ function
* During the treatment period and for ≥7 days after the last dose of BCG, male participants are EITHER abstinent from heterosexual intercourse as their preferred and usual lifestyle and agree to remain abstinent, OR, must agree to use contraception unless confirmed to be azoospermic
* Female participants who are not pregnant, not breastfeeding, and either not a woman of child bearing potential (WOCBP); or are a WOCBP who agrees to use a contraception method that is highly effective or remains abstinent from heterosexual intercourse during the treatment period and for ≥7 days after the last dose of BCG or 120 days after the last dose of pembrolizumab, whichever comes last
BCG Post-induction Cohort (Cohort A) Only
* Has been treated with one adequate course of BCG induction therapy for the treatment of HR NMIBC
* Following adequate BCG induction therapy, must have persistent or recurrent HR NMIBC
Exclusion Criteria:
* Has a history of or concurrent locally advanced (i.e., T2, T3, T4) or metastatic UC
* Has concurrent extra-vesical (i.e, urethra, ureter, renal pelvis) non-muscle invasive urothelial carcinoma or a history of extra-vesical non-muscle invasive UC
* Has received prior therapy with anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor
* Has received prior systemic anti-cancer therapy including investigational agents within 4 weeks of start of study treatment
* Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks of start of study treatment
* Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy or any other form of immunosuppressive therapy within 7 days of start of study treatment
* Has a known additional malignancy that is progressing or requires active treatment within the past 3 years
* Has an active autoimmune disease that has required systemic treatment in past 2 years
* Has a history of (non-infectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease
* Has one or more of the following contraindications to BCG: prior BCG sepsis or systemic infection, total bladder incontinence, or an adverse experience to a previous BCG instillation that resulted in treatment discontinuation and precludes retreating with BCG
* Has an active infection or diagnosis requiring systemic antimicrobial therapy
* Has a known history of human immunodeficiency virus (HIV) infection
* Has a known history of Hepatitis B or known active Hepatitis C virus infection
* Has current active tuberculosis
* Has had an allogenic-tissue/solid organ transplant
* Has any contraindication(s) to IV contrast or is otherwise unable to have screening imaging with IV contrast performed
BCG Post-induction Cohort (Cohort A) Only - Has persistent T1 disease following an induction course of BCG
BCG Naïve Cohort (Cohort B) Only
\- Has received any prior treatment with BCG for their NMIBC within the past 2 years prior to study entry
Primary outcome measure(s)
Complete Response Rate (CRR) by Blinded Independent Central Review (BICR) (Cohort A) — Up to ~3.5 years CRR is defined as the percentage of participants with carcinoma in situ (CIS) achieving a complete response (CR).
Event-Free Survival (EFS) (Cohort B) — Up to ~5 years EFS is defined as the time from randomization until urothelial carcinoma (UC)-defined event, or death due to any cause.
Trial sites (209)
Facility
City
Region
Status
Alaska Urological Institute dba Alaska Clinical Research Center ( Site 1083)
Anchorage
Alaska
Mayo Clinic in Arizona - Phoenix ( Site 1094)
Phoenix
Arizona
Del Sol Research Management, LLC ( Site 1096)
Tucson
Arizona
UCLA Hematology/Oncology - Westwood (Building 200 Suite 140)-Department of Urology/Institute of Uro ( Site 1052)
Los Angeles
California
University of California Irvine Medical Center ( Site 1061)
Orange
California
Genesis Research LLC ( Site 1065)
Torrance
California
Colorado Clinical Research ( Site 1100)
Lakewood
Colorado
Urological Research Network ( Site 1106)
Hialeah
Florida
Mayo Clinic in Florida-Urology ( Site 1097)
Jacksonville
Florida
University of Miami Hospital and Clinics, Sylvester Cancer Center ( Site 1056)
Miami
Florida
Woodlands Medical Specialists, PA ( Site 8002)
Pensacola
Florida
Emory School of Medicine ( Site 1076)
Atlanta
Georgia
Advanced Urology ( Site 1092)
Roswell
Georgia
Northwestern Memorial Hospital ( Site 1101)
Chicago
Illinois
Wichita Urology Group ( Site 1086)
Wichita
Kansas
Ochsner LSU Health Shreveport - Regional Urology ( Site 1099)
Shreveport
Louisiana
Henry Ford Hospital ( Site 1062)
Detroit
Michigan
Michigan Institute of Urology ( Site 1077)
Troy
Michigan
Coastal Urology Associates ( Site 1055)
Brick
New Jersey
Morristown Medical Center ( Site 1090)
Morristown
New Jersey
Rutgers Cancer Institute of New Jersey ( Site 1059)
New Brunswick
New Jersey
St. Peter's Hospital Cancer Care Center ( Site 1087)
Albany
New York
R.J. Zuckerberg Cancer Center ( Site 1080)
Lake Success
New York
Veterans Affairs New York Harbor Healthcare System-PCF COE ( Site 1112)
New York
New York
Laura and Isaac Perlmutter Cancer Center at NYU Langone Health ( Site 1074)
New York
New York
Associated Medical Professionals of NY ( Site 1078)
Syracuse
New York
TriState Urologic Services PSC Inc. dba The Urology Group ( Site 1091)
Cincinnati
Ohio
University Hospitals Cleveland Medical Center ( Site 1066)
Cleveland
Ohio
Ohio State University Arthur G James Cancer Hospital & Richard J Solove Research Institute ( Site 1067)
Columbus
Ohio
OHSU Knight Cancer Institute ( Site 1075)
Portland
Oregon
Oregon Urology Institute ( Site 1098)
Springfield
Oregon
MidLantic Urology ( Site 1071)
Bala-Cynwyd
Pennsylvania
Lancaster Urology ( Site 1079)
Lancaster
Pennsylvania
University of Pennsylvania ( Site 1088)
Philadelphia
Pennsylvania
Carolina Urologic Research Center ( Site 1085)
Myrtle Beach
South Carolina
Urology Associates [Nashville, TN] ( Site 1072)
Nashville
Tennessee
Urology Clinics of North Texas, PLLC ( Site 1064)
Dallas
Texas
University Of Texas Southwestern Medical Center ( Site 1053)
Dallas
Texas
Texas Oncology-Fort Worth Cancer Center ( Site 8003)
Fort Worth
Texas
Houston Metro Urology ( Site 1111)
Houston
Texas
+ 169 more sites — see the full list on the official registry below.
This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.
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