Pembrolizumab in Muscle-invasive Bladder Cancer

Inclusion Criteria: Subject must meet all of the following applicable inclusion criteria to participate in this study: * Written informed consent and HIPAA authorization for release of personal health information prior to registration. NOTE: HIPAA authorization may be included in the informed consent or obtained separately. * Age ≥ 18 years at the time of consent. * ECOG Performance Status of ≤ 1 within 28 days prior to registration. * Histological evidence of clinically localized muscle-invasive urothelial cancer of the bladder. Clinical stage cT2-3N0M0. N0 will be considered the absence of radiographically enlarged lymph nodes on baseline imaging. Patients with lymph nodes \<1 cm in long axis on imaging may be eligible but must be discussed with the sponsor investigator. * Have undergone a standard of care maximal transurethral resection of bladder tumor ≤ 60 days prior C1D1. Maximal TURBT is defined as a macroscopically complete resection of bladder tumor when safely possibly per the treating urologist. Patients who cannot safely undergo maximal TURBT as per their treating urologist are eligible for enrollment but should be discussed with the sponsor investigator. * All subjects must have adequate transurethral resection of bladder tumor tissue available for submission (i.e., at least 15 unstained slides or paraffin block) identified during screening. This tissue can be from the maximal restaging TURBT, a prior diagnostic TURBT revealing muscle-invasive bladder cancer, or both specimens. Subjects without available archival tissue must be discussed with the sponsor-investigator. * Decline cisplatin-based neoadjuvant chemotherapy or be considered cisplatin-ineligible based on at least one of the following modified criteria (as ECOG 0-1 is required for eligibility): * Creatinine clearance \< 60 mL/min (but ≥ 30 mL/min) * Grade ≥ 2 hearing loss (per CTCAE criteria v5) * Grade ≥ 2 neuropathy (per CTCAE criteria v5) * New York Heart Association Class III heart failure * Demonstrate adequate organ function as defined below. All screening labs to be obtained within 28 days prior to registration. * Hematological * Absolute Neutrophil Count (ANC): ≥ 1.5 x 10\^9/L * Hemoglobin (Hgb): ≥ 9 g/dL * Platelets: ≥ 100 x 10\^9/L * Renal * Creatinine OR: Creatinine ≤ 1.5 × ULN OR * Calculated creatinine clearance: creatinine clearance ≥ 30 mL/min * Hepatic * Bilirubin: ≤ 1.5 ×ULN OR direct bilirubin ≤ ULN for participants with total bilirubin levels \> 1.5 × ULN * Aspartate aminotransferase (AST): ≤ 2.5 × ULN * Alanine aminotransferase (ALT): ≤ 2.5 × ULN * Women of childbearing potential (WOCP) must have a negative serum or urine pregnancy test a maximum of 24-hours before the first dose of study drug. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required. WOCBP must agree to use contraception. * A male participant must agree to use contraception. Exclusion Criteria: Subjects meeting any of the criteria below may not participate in the study: * Prior systemic chemotherapy for muscle-invasive urothelial cancer of the bladder. * Prior malignancy active within the previous 2 years except for locally curable cancers that have been apparently cured. Patients with intermediate or lower risk prostate cancer as defined by the National Comprehensive Cancer Network (NCCN) risk stratification guidelines may be eligible for enrollment. * Prior radiation therapy for bladder cancer. * Active infection requiring systemic therapy. * Has a known history of Hepatitis B or C. NOTE: Patients with a past or resolved HBV infection (defined as the presence of hepatitis B core antibody \[anti-HBc\] and absence of HBsAg) are eligible. Patients positive for hepatitis C (HCV) antibody are eligible only if polymerase chain reaction is negative for HCV RNA. NOTE: no testing for Hepatitis B and Hepatitis C is required unless mandated by local health authority. * Has a known history of Human Immunodeficiency Virus (HIV) infection. NOTE: no testing for HIV is required unless mandated by local health authority. * Has a known history of active TB (Bacillus Tuberculosis). * Pregnant or breastfeeding (NOTE: breast milk cannot be stored for future use while the mother is being treated on study). * Has received prior therapy with an 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 (eg, CTLA-4, OX 40, CD137). * Has received a live or live-attenuated vaccine within 30 days prior to the first dose of study drug. Administration of killed vaccines is allowed. * 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 of immunosuppressive therapy within 7 days prior to the first dose of study drug. * Has severe hypersensitivity (≥ Grade 3) to pembrolizumab and/or any of its excipients. * Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment and is allowed. * Has a history of (non-infectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease. * Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the subject's participation for the full duration of the study, or is not in the best interest of the subject to participate, in the opinion of the treating investigator. * Has had an allogenic tissue/solid organ transplant. * Is currently receiving an investigational agent or has received an investigational agent or used an investigational device within 28 days of study registration.