Pembrolizumab and Combination Chemotherapy Before Surgery for the Treatment of Muscle-Invasive Bladder Cancer

Inclusion Criteria

• Participants must have histologically confirmed diagnosis of muscle invasive bladder cancer (cT2-T4a, N0-N1, M0 clinical stage per American Joint Commission on Cancer [AJCC]). Clinical node-positive (N1) patients are eligible provided the lymph nodes (LNs) are confined to the true pelvis and are within the planned surgical LN dissection template
• Histology must be either pure or predominant non-urothelial histology (noted on any TURBT)
• Participants must be deemed eligible for cisplatin-based chemotherapy, radical cystectomy (RC) and pelvic lymph node dissection (PLND) by urologist and medical oncologist
• Patients must agree to undergo curative intent surgery
• TURBT that showed muscularis propria invasion should be within 12 weeks prior to beginning study therapy. Patients must have available tumor tissue from either initial or repeat TURBT, prior to starting study therapy. Archival tumor tissue sample of a tumor lesion (TURBT specimen) should be provided and must contain muscle invasive component, at least >= T2 tumor. Formalin-fixed, paraffin embedded (FFPE) tissue blocks are preferred to slides. If submitting unstained cut slides, newly cut slides should be submitted to the testing laboratory, preferably within 14 days from the date slides are cut if possible. Patient must be willing to provide tumor tissue for research. Research samples will not be used for any studies unrelated to this trial
• Must have clinical non-metastatic bladder cancer (M0) determined by cross-sectional computed tomography (CT) chest, abdomen and pelvis (CAP) or magnetic resonance imaging (MRI) imaging
• A male participant must agree to use a contraception during the treatment period and for at least 180 days after the last dose of study treatment and refrain from donating sperm during this period
• A female participant is eligible to participate if she is not pregnant , not breastfeeding, and at least one of the following conditions applies:
• Not a woman of childbearing potential (WOCBP) OR
• A WOCBP who agrees to follow the contraceptive guidance during the treatment period and for at least 180 days after the last dose of study treatment
• The participant (or legally acceptable representative if applicable) provides written informed consent for the trial
• Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1. Evaluation is to be performed within 7 days prior to the date of enrollment
• Absolute neutrophil count (ANC) >= 1500/uL (collected within 10 days prior to the start of study treatment)
• Platelets >= 100 000/uL (collected within 10 days prior to the start of study treatment)
• Hemoglobin >= 9.0 g/dL or >= 5.6 mmol/L (collected within 10 days prior to the start of study treatment)
• Criteria must be met without erythropoietin dependency and without packed red blood cell (pRBC) transfusion within last 2 weeks
• Serum creatinine = = 50 ml/min (collected within 10 days prior to the start of study treatment). Measured or calculated creatinine clearance (GFR can be used in place of creatinine clearance; 24-hour urine collection can be used for more accurate estimate as needed)
• Creatinine clearance (CrCl) should be calculated per institutional standard
• Total bilirubin = 1.5 x ULN (collected within 10 days prior to the start of study treatment)
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) and alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase [SGPT]) = 10 mg daily of prednisone dose equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug
• Has known additional malignancy that is progressing or has required active systemic treatment within the past 2 years. Note: Participants with basal cell carcinoma or squamous cell carcinoma of the skin, or any carcinoma in situ that have undergone potentially curative therapy are not excluded. Low/intermediate risk prostate cancer with prior poten