Study

Overview

Official Title: A Phase 3, Randomized, Comparator-controlled Clinical Trial to Study the Efficacy and Safety of Pembrolizumab (MK-3475) in Combination with Bacillus Calmette-Guerin (BCG) in Participants with High-risk Non-muscle Invasive Bladder Cancer (HR NMIBC) that is either Persistent or Recurrent Following BCG Induction or that is Naïve to BCG Treatment (KEYNOTE-676)

This study is designed to assess the antitumor efficacy and safety of pembrolizumab in combination with BCG, compared to BCG monotherapy, in participants with HR NMIBC that is either persistent or recurrent following adequate BCG induction (Cohort A), or that is naïve to BCG treatment (Cohort B). The primary hypothesis for Cohort A is that the combination of pembrolizumab plus BCG has a superior complete response rate (CRR) as assessed by central pathology review compared to BCG in participants with carcinoma in situ (CIS). The primary hypothesis for Cohort B is that the combination of pembrolizumab plus BCG (either reduced maintenance or full maintenance) has a superior Event Free Survival (EFS) compared to BCG.

Study Type:

Interventional

Study Phase:

Phase 3

Estimated Enrollment:

1405

Study Start Date:

December 2018

Estimated Study Completion Date:

October 2028

Estimated Primary Completion Date:

December 2025

Eligibility

Ages Eligible for Study:

18 years and older

Genders Eligible for Study:

All

Accepts Healthy Volunteers:

No

CRITERIA

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

Locations

United States Toll Free Number 1-800-770-4674

Phoenix, Arizona, 85054
Tucson, Arizona, 85704
Orange, California, 92868
Torrance, California, 90505
Lakewood, Colorado, 80228
Hialeah, Florida, 33016
Jacksonville, Florida, 32224
Miami, Florida, 33136
Atlanta, Georgia, 30322
Roswell, Georgia, 30076
Chicago, Illinois, 60611
Shreveport, Louisiana, 71106
Detroit, Michigan, 48202
Troy, Michigan, 48084
Morristown, New Jersey, 07960
Lake Success, New York, 11042
New York, New York, 10010
New York, New York, 10016
Cincinnati, Ohio, 45212
Columbus, Ohio, 43210
Springfield, Oregon, 97477
Bala Cynwyd, Pennsylvania, 19004
Lancaster, Pennsylvania, 17604
Philadelphia, Pennsylvania, 19104
Myrtle Beach, South Carolina, 29572
Nashville, Tennessee, 37209
Dallas, Texas, 75231
Dallas, Texas, 75390
Houston, Texas, 77027
San Antonio, Texas, 78229
Burlington, Vermont, 05401
Virginia Beach, Virginia, 23462

Canada Study Coordinator 4185411000

Results

No Study Results Posted

Plain Language Summaries

Protocols

Protocol Plain Language Summary - MK-3475-676

Study Detail

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)