Pembrolizumab in Treating Patients With Small Bowel Adenocarcinoma That is Metastatic or Locally Advanced and Cannot Be Removed by Surgery

This phase II trial studies how well pembrolizumab works in treating patients with small bowel adenocarcinoma that has spread to other places in the body or that cannot be removed by surgery. Monoclonal antibodies, such as pembrolizumab, may interfere with the ability of tumor cells to grow and spread.

PRIMARY OBJECTIVES: I. To determine whether pembrolizumab administered to small bowel adenocarcinoma (SBA) patients demonstrates antitumor activity as measured by the confirmed response rate. SECONDARY OBJECTIVES: I. To assess survival endpoints (overall survival \[OS\], progression free survival \[PFS\]), including stratified analysis by tumor site. II. To assess whether pembrolizumab is safe in SBA patients by assessing adverse events. TERTIARY OBJECTIVES: I. To determine whether PD-L1 expression, as measured by immunohistochemistry (IHC), or microsatellite instability (MSI) status is associated with the response rate overall. II. To determine if Bim levels in tumor-reactive CD11ahighPD-1+CD8+ peripheral blood T cells can objectively monitor responses to pembrolizumab and to determine if excessive release of soluble B7-H1 (soluble \[s\]PD-L1) by the tumor leads to Bim upregulation and treatment resistance in SBA. III. To determine if other tissue-based factors, such as total mutational burden, correlate with response to pembrolizumab. OUTLINE: Patients receive pembrolizumab intravenously (IV) over 30 minutes on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 3 months until disease progression, and then every 6 months for up to 5 years.