Efficacy and Safety of Pembrolizumab (MK-3475) in Combination With Chemoradiotherapy (CRT) Versus CRT Alone in Muscle-invasive Bladder Cancer (MIBC) (MK-3475-992/KEYNOTE-992)

Inclusion Criteria:

• Has a histologically confirmed initial diagnosis of muscle-invasive bladder cancer (MIBC) with predominant urothelial histology

• Has clinically nonmetastatic bladder cancer (N0M0)

• Has planned and is eligible to receive chemoradiotherapy (CRT) and one of theprotocol-specified radiosensitizing chemotherapy regimens

• Has Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2

• Demonstrates adequate organ function

• Male participants are eligible to participate if they agree to the following duringthe intervention period and for at least 90 days after the last dose of CRTtreatment:

• Refrain from donating sperm

• Be abstinent from heterosexual intercourse as their preferred and usuallifestyle (abstinent on a long term and persistent basis) and agree to remainabstinent; or must agree to use contraception unless confirmed to beazoospermic

• A female participant is eligible to participate if she is not pregnant orbreastfeeding, and at least one of the following conditions applies:

• Is not a woman of childbearing potential (WOCBP)

• Is a WOCBP and using a contraceptive method that is highly effective (with afailure rate of <1% per year), with low user dependency or be abstinent fromheterosexual intercourse as their preferred and usual lifestyle (abstinent on along term and persistent basis), during the intervention period and for atleast 180 days the time needed to eliminate each study intervention after thelast dose of study intervention; and agrees not to donate eggs (ova, oocytes)to others or freeze/store for her own use for the purpose of reproductionduring this period. The length of time required to continue contraception foreach study intervention is as follows: MK-3475 - 120 days and CRT - 180 days

Exclusion Criteria:

• Has the presence of diffuse carcinoma in situ (CIS) (multiple foci of CIS)throughout the bladder

• Has the presence of urothelial carcinoma (UC) at any site outside of the urinarybladder in the previous 2 years except for Ta stage/T1 stage/CIS of the upper tractif the participant has undergone a complete nephroureterectomy

• Has a known additional malignancy that is progressing or has required active therapywithin the past 3 years, except basal cell carcinoma of the skin, squamous cellcarcinoma of the skin, superficial bladder cancer or other carcinoma in situ thathas undergone potentially curative therapy

• Has the presence of bilateral hydronephrosis

• Has limited bladder function with frequency of small amounts of urine (< 30 mL),urinary incontinence, or requires self-catheterization or a permanent indwellingcatheter

• Has received prior pelvic/local radiation therapy for any reason or anyantineoplastic treatment for muscle-invasive bladder cancer (MIBC). Treatment fornon-muscle invasive bladder cancer (NMIBC) with intravesical instillation therapythat was completed ≥28 days prior to randomization is allowed. Prior systemictreatment of NMIBC is not permitted.

• Received prior therapy with an anti-PD-1 (programmed cell death protein 1),anti-PD-L1 (programmed death-ligand 1), or anti-PD-L2 (programmed cell death 1ligand 2), or with an agent directed to another stimulatory or coinhibitory T-cellreceptor (e.g., CTLA-4 [cytotoxic T-lymphocyte-associated protein 4], OX 40, orCD137 [cluster of differentiation 137])

• Has received a live vaccine within 30 days before the first dose of study medication

• Is currently participating in or has participated in a study of an investigationalagent or has used an investigational device within 4 weeks before the first dose ofstudy medication

• Has known severe hypersensitivity (≥Grade 3) to the selected chemotherapy regimen,and/or any of their excipients and excipients of pembrolizumab

• Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form ofimmunosuppressive therapy within 7 days before the first dose of study medication

• Has an active autoimmune disease that has required systemic treatment in the past 2years (ie, with use of disease modifying agents, corticosteroids orimmunosuppressive drugs). Replacement therapy (eg, thyroxine, insulin, orphysiologic corticosteroid replacement therapy for adrenal or pituitaryinsufficiency) is not considered a form of systemic treatment and is allowed

• Has a history of non-infectious pneumonitis that required steroids or has currentpneumonitis

• Has an active infection requiring systemic 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 a known history of active tuberculosis (TB; Bacillus tuberculosis)

• Has a known psychiatric or substance abuse disorder that would interfere with theparticipant's ability to cooperate with the requirements of the study

• Has had an allogenic tissue/solid organ transplant