Pembrolizumab and Palliative Radiation Therapy in Treating Patients With Metastatic Esophagus, Stomach, or Gastroesophageal Junction Cancer

Inclusion Criteria

• Documented informed consent of the participant
• Willing to provide tumor tissue amenable to ultrasound or computed tomography (CT)-guided biopsy for biomarker analyses
• Patients with malignant ascites are permitted to participate and provide ascites samples for biomarker analyses
• Patents receiving radiation to a single metastatic site in which only the primary tumor is accessible for biopsy by endoscopy will also be eligible
• Eastern Cooperative Oncology Group (ECOG) performance status of = = 3 months
• Diagnosis of metastatic squamous cell carcinoma and/or adenocarcinoma of the esophagus, gastroesophageal junction, or stomach in need of palliative radiotherapy to the primary tumor or a single metastatic site for symptoms such as pain, dysphagia, and/or gastrointestinal bleeding
• Patients with adenocarcinoma histology and known human epidermal growth factor receptor 2 (HER2) overexpressing disease are permitted to participate if the progressed or are intolerant of prior trastuzumab-containing therapy
• Measurable metastatic sites of disease outside of the target lesion undergoing palliative radiation based on RECIST 1.1 as assessed by the investigator
• Have no limits on prior lines of therapy or may be treatment-naive if in need of palliative RT provided the patient has not received prior anti-programmed cell death protein 1(PD-1), anti-programmed cell death 1 ligand 1 (PD-L1), or anti-programmed cell death 1 ligand 2 (PD-L2) therapy
• Absolute neutrophil count (ANC) >= 1,500/mm^3
• Platelets >= 100,000/mm^3
• Hemoglobin >= 9 g/dL
• May receive transfusion to meet this goal
• Total serum bilirubin = 1.5 x ULN
• Albumin >= 2.5 mg/dL
• Aspartate aminotransaminase (AST) and alanine aminotransferase (ALT) = = 60 mL/min if creatinine levels > 1.5 x ULN
• Glomerular filtration rate (GFR) can also be used in place of creatinine or creatinine clearance (CrCl)
• If not receiving anticoagulants: international normalized ratio (INR) OR prothrombin (PT) = 1 year
• Male: use an adequate method of contraception starting with the first dose of study therapy through 120 days after the last dose of study therapy

Exclusion Criteria

• Anti-PD-1, anti-PD-L1, or anti-PD-L2 agents
• Prior radiation therapy within the field of the target lesion that in the opinion of the treating radiation oncologist would preclude further palliative radiation to a dose of 30 gray (Gy)
• Anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study day 1 or who has not recovered (i.e., =< grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier
• Chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study day 1 or who has not recovered (i.e., =< grade 1 or at baseline) from adverse events due to a previously administered agent
• Note: Subjects with =< grade 2 neuropathy are an exception to this criterion and may qualify for the study
• Note: If subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy
• Live vaccine within 30 days of planned start of study therapy
• Note: Seasonal influenza vaccines for injection are generally inactivated flu vaccines and are allowed; however intranasal influenza vaccines (e.g., Flu-Mist) are live attenuated vaccines, and are not allowed
• Immunosuppressive therapy within 7 days prior to the first dose of trial treatment
• Investigational device within 4 weeks of the first dose of treatment
• Currently receiving an investigational agent
• About to undergo palliative radiation for a symptomatic central nervous system (CNS) metastasis
• Systemic steroid therapy
• Hypersensitivity to pembrolizumab or any of its excipients
• Diagnosis of immunodeficiency
• Active autoimmune disease that has required systemic treatment in the past 2 years (i.e., with use of disease modifying agents, corticosteroids or immunosuppressive dr