Pembrolizumab Before Surgery for the Treatment of Mismatch Repair Deficient Locally Advanced Solid Cancers

Inclusion Criteria

• Male/female participants who are at least 18 years of age on the day of signing informed consent with histologically confirmed diagnosis of solid cancer
• Solid cancer that is deficient in mismatch repair (dMMR) or microsatellite instability high (MSI-H) as determined by one of three methods:
• Immunohistochemistry determined dMMR by complete loss of MLH1, PMS2, MSH2 or MSH6
• Polymerase chain reaction (PCR) determined microsatellite instability at > 30% of tested microsatellites
• Next-generation sequencing determined MSI-H based upon instability at multiple microsatellites as determined by the specific next generation sequencing panel
• Locally advanced cancer defined as either an unresectable primary cancer or a resectable primary cancer with a high chance of recurrence (defined as an estimated greater or equal to 20% chance of recurrence by the treating physician). A resectable primary may include locoregional disease, as long as all disease is felt by the treating physician to be in a resectable distribution
• The participant (or legally acceptable representative if applicable) provides written informed consent for the trial
• Have measurable disease based on Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1 (unless discussed and approved by study principal investigator [PI])
• Have available archival tumor tissue. Availability will be met as long as a request to obtain formalin-fixed, paraffin embedded (FFPE) tissue blocks (preferred) or slides has been made (unless discussed and approved by study PI)
• Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1. Evaluation of ECOG is to be performed within 7 days prior to the date of signing study consent
• 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 (120 days [corresponding to time needed to eliminate any study treatment(s) plus 30 days (a menstruation cycle) for risk of genotoxicity]) after the last dose of study treatment
• Absolute neutrophil count (ANC) >= 1500/uL (within 14 days prior to the start of study treatment)
• Platelets >= 100 000/uL (within 14 days prior to the start of study treatment)
• Hemoglobin >= 8.0 g/dL or >= 5.6 mmol/L (within 14 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
• Creatinine = = 30 mL/min for participant with creatinine levels > 1.5 x institutional ULN (within 14 days prior to the start of study treatment)
• Creatinine clearance (CrCl) should be calculated per institutional standard
• Total bilirubin = 1.5 x ULN (within 14 days prior to the start of study treatment)
• Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT]) and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) = = 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 (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment
• Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis
• Has an active infection requiring systemic therapy
• Has a known history of human immunodeficiency virus (HIV)
• Has a known history of hepatitis B (defined as hepatitis B surface antigen [HBsAg] reactive) or known active hepatitis C virus (defined as HCV ribonucleic acid [RNA] [qualitative] is detected) infection. Note: no testing for hepatitis B and