CD8+ T Cell Therapy and Pembrolizumab in Treating Patients with Metastatic Gastrointestinal Tumors

Inclusion Criteria

• Histopathologic documentation of pancreatic adenocarcinoma, colorectal adenocarcinoma, cholangiocarcinoma, esophageal cancer and gastric cancer with radiographic evidence of metastatic disease
• Eastern Cooperative Oncology Group (ECOG)/Zubrod performance status of 0 or 1
• Women of childbearing potential (WOCBP) must be using an adequate method of contraception to avoid pregnancy throughout the study in such a manner that the risk of pregnancy is minimized; suggested precautions should be used to minimize the risk or pregnancy for at least 1 month before start of therapy, and while women are on study for at least 8 weeks after pembrolizumab is stopped; WOCBP include any female who has experienced menarche and who has not undergone successful surgical sterilization (hysterectomy, bilateral tubal ligation or bilateral oophorectomy) or is not postmenopausal; acceptable forms of birth control include condom, diaphragm, hormonal, intrauterine device (IUD), or sponge plus spermicide; abstinence is also an acceptable form of birth control
• Men must be willing and able to use an acceptable method of birth control, during and for at least 3 months after completion of the study, if their sexual partners are WOCBP
• Willing and able to give informed consent
• Adequate vein access: consider peripherally inserted central catheter (PICC) or other central line
• Patients must have adequate tissue (fresh or frozen) available or planned removal of adequate tissue for analysis; at least 250 mg of tumor are needed for peptide elution; there is no specific time limit on how long the tissue can remain frozen prior to use
• Patients can have any lines (including zero) of prior therapy to sign consent prior to tissue harvest
• Toxicity related to prior therapy must either have returned to =< grade 1, baseline, or been deemed irreversible
• ELIGIBILITY FOR TREATMENT: ECOG/Zubrod performance status of 0 to 2
• Bi-dimensionally measurable disease by radiographic imaging (computed tomography [CT] scan) that represents at least one measurable lesion per Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1
• At least 4 weeks must have elapsed since the last chemotherapy, radiotherapy or major surgery
• Toxicity related to prior therapy must either have returned to less than or equal to grade 1, baseline, or been deemed irreversible
• Subjects must have received at least one line of chemotherapy prior to receiving adoptive T cell therapy and should have exhausted standard of care systemic therapy options; the decision to implement the T cell therapy will be at the discretion of the treating physician; the timing and total exposure to chemotherapy will depend on the tumor type in question (more systemic options for breast cancer; fewer for gastric cancer, for example); due to the heterogeneity of tumors being treated in this protocol, the discretion of the treating physician in terms of timing of immunotherapy will be critical

Exclusion Criteria

• EXCLUSION FOR ENROLLMENT: Any other malignancy from which the patient has been disease-free for less than 5 years, with the exception of adequately treated and cured basal or squamous cell skin cancer, superficial bladder cancer, and carcinoma in situ of the cervix
• Pregnant women, nursing mothers, men or women of reproductive ability who are unwilling to use effective contraception; women of childbearing potential with a positive pregnancy test within 3 days prior to entry
• Significant cardiovascular abnormalities as defined by any one of the following: * Congestive heart failure New York Heart Association (NYHA) classes II-IV; patients with asymptomatic class I congestive heart failure (CHF) may participate in conjunction with a cardiology consultation * Clinically significant hypotension * Symptoms of coronary artery disease * Presence of arrhythmias in electrocardiography (EKG) requiring drug therapy
• Active and untreated central nervous system (CNS) metastases (including metastasis identified during screening MRI or contrast CT); patients with asymptomatic, treated metastases may be eligible if their lesion(s) have demonstrated stability over 2 months
• Autoimmune disease: patients with a history of inflammatory bowel disease are excluded from this study, as are patients with a history of autoimmune disease (e.g. systemic lupus erythematosus, vasculitis, infiltrating lung disease) whose possible progression during treatment would be considered by the investigator to be unacceptable
• Any underlying medical or psychiatric condition, which in the opinion of the investigator, will make the administration of study drug hazardous or obscure the interpretation of adverse events, such as a condition associated with frequent diarrhea
• White blood cell (WBC) less than or equal to 2000/uL
• Hematocrit (Hct) less than or equal to 24% or hemoglobin (Hgb) less than or equal to 8 g/dL
• Absolute neutrophil count (ANC) less than or equal to 1000
• Platelets less than or equal to 75,000
• Creatinine greater than or equal to 1.5 x upper limit of normal (ULN) OR creatinine clearance > 50 ml/min/1.73 m^2 for patients with creatinine levels above institutional normal limits
• Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) greater than or equal to 2.5 x ULN
• Bilirubin greater than or equal to 2.0 x ULN
• Positive screening tests for human immunodeficiency virus (HIV), hepatitis (Hep) B, and Hep C; if positive results are not indicative of true active or chronic infection, the patient can be treated
• EXCLUSION CRITERIA FOR TREATMENT: WBC less than or equal to 2000/uL
• EXCLUSION CRITERIA FOR TREATMENT: Hct less than or equal to 24%
• EXCLUSION CRITERIA FOR TREATMENT: Hgb less than or equal to 8 g/dL
• EXCLUSION CRITERIA FOR TREATMENT: ANC less than or equal to 1000
• EXCLUSION CRITERIA FOR TREATMENT: Platelets less than or equal to 75,000
• EXCLUSION CRITERIA FOR TREATMENT: Creatinine greater than or equal to 1.5 x ULN OR creatinine clearance > 50 ml/min/1.73m^2 for patients with creatinine levels above institutional normal limits
• EXCLUSION CRITERIA FOR TREATMENT: AST/ALT greater than or equal to 2.5 x ULN
• EXCLUSION CRITERIA FOR TREATMENT: Bilirubin greater than or equal to 2.0 x ULN
• Steroids are not permitted 3 days prior to T cell infusion and concurrently during therapy
• Uncontrolled concurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
• Any non-oncology vaccine therapy used for the prevention of infectious disease within 1 month before or after any anti-programmed cell death protein 1 (PD1) monoclonal antibody (anti-PD-1) dose
• After the T cell infusion, patients may not be on any other treatments for their cancer aside from those included in the treatment section of the protocol
• Coagulation 1.5 x ULN unless participant is receiving anticoagulant therapy as long as prothrombin time (PT) or a partial thromboplastin time (PTT) is within therapeutic range of intended use of anticoagulants