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)

Inclusion Criteria:

• Have locally and blinded independent central review (BICR)-confirmed histologicaldiagnosis of high-risk non-muscle invasive (T1, high grade Ta and/or CIS) UC of thebladder

• Has undergone cystoscopy/ transurethral resection of bladder tumor (TURBT) to removeall 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, maleparticipants are EITHER abstinent from heterosexual intercourse as their preferredand usual lifestyle and agree to remain abstinent, OR, must agree to usecontraception unless confirmed to be azoospermic

• Female participants who are not pregnant, not breastfeeding, and either not a womanof child bearing potential (WOCBP); or are a WOCBP who agrees to use a contraceptionmethod that is highly effective or remains abstinent from heterosexual intercourseduring the treatment period and for ≥7 days after the last dose of BCG or 120 daysafter 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 treatmentof 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-muscleinvasive 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 withan agent directed to another stimulatory or co-inhibitory T-cell receptor

• Has received prior systemic anti-cancer therapy including investigational agentswithin 4 weeks of start of study treatment

• Is currently participating in or has participated in a study of an investigationalagent or has used an investigational device within 4 weeks of start of studytreatment

• Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapyor any other form of immunosuppressive therapy within 7 days of start of studytreatment

• Has a known additional malignancy that is progressing or requires active treatmentwithin the past 3 years

• Has an active autoimmune disease that has required systemic treatment in past 2years

• Has a history of (non-infectious) pneumonitis/interstitial lung disease thatrequired steroids or has current pneumonitis/interstitial lung disease

• Has one or more of the following contraindications to BCG: prior BCG sepsis orsystemic infection, total bladder incontinence, or an adverse experience to aprevious BCG instillation that resulted in treatment discontinuation and precludesretreating 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 screeningimaging 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 yearsprior to study entry