Neoantigen Peptide Vaccine for the Treatment of Pancreatic Cancer

Inclusion Criteria

• Histologically or cytologically confirmed diagnosis of pancreatic adenocarcinoma; mixed histology will be included as long as the predominant histology is adenocarcinoma
• Completed an R0 or R1 surgical resection as determined by pathology
• Pathology review demonstrates tumor cellularity no less than 30% in quantities sufficient to obtain 6-8 1mm biopsies from the original formalin fixed paraffin embedded (FFPE) blocks
• At least 18 years of age
• Life expectancy of > 12 months
• Eastern Cooperative Oncology Group (ECOG) performance status =< 2
• White blood cell (WBC) >= 3,000/uL
• Absolute neutrophil count >= 1,500/uL
• Platelets >= 100,000/uL
• Total bilirubin =< 1.5 X institutional upper limit of normal * (Subjects with Gilbert’s syndrome may be enrolled despite a total bilirubin level >1.5 mg/dL if their conjugated bilirubin is <1.5 x upper limit of normal [ULN])
• Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 2.5 X institutional upper limit of normal
• Creatinine =<1.5 X institutional upper limit of normal
• International normalized ratio (INR) and activated partial thromboplastin time (PTT) < 1.5 x ULN provided the patient is not on anticoagulation therapy
• Patients who have had a stent placed for biliary obstruction can be included in the study provided serum bilirubin at time of enrollment is within protocol limits
• Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control, abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she must inform her treating physician immediately
• Able to understand and willing to sign an Institutional Review Board (IRB) approved written informed consent document.
• STEP 1
• Completed adjuvant chemotherapy: *. Initiation of adjuvant chemotherapy within 16 weeks of surgery * Completion of at least 4 months of adjuvant chemotherapy with gemcitabine/fluorouracil/irinotecan/leucovorin/oxaliplatin (FOLFIRINOX), or similar adjuvant chemotherapy at the discretion of the patient’s medical oncologist * Additional chemoradiation therapy as recommended by the patient’s medical oncologist * Reimaging post-completion of chemotherapy demonstrates no evidence of recurrent disease and CA 19-9 is less than 92.5 u/mL * Dose modifications and/or delays in adjuvant chemotherapy is at the discretion of the treating physician
• There is a 1 week washout prior to day 1 of vaccine for patients on daily systemic steroids at doses exceeding 10 mg prednisone

Exclusion Criteria

• Evidence of neuroendocrine tumor, duodenal adenocarcinoma, or ampullary adenocarcinoma
• Received neoadjuvant chemotherapy for their pancreatic adenocarcinoma
• Evidence of disease recurrence or metastasis following surgical resection at any time prior to the first vaccination administration. Most patients will undergo restaging midway through adjuvant chemotherapy and at the completion of therapy; however, timing of imaging is at the discretion of the patient’s medical oncologist
• History of other malignancy =< 3 years previous with the exception of basal cell or squamous cell carcinoma of the skin which were treated with local resection only, carcinoma in situ of the cervix, or lobular breast carcinoma in situ (LCIS)/ductal breast carcinoma in situ (DCIS) of the breast
• Known allergy, or history of serious adverse reaction to vaccines or TLR agonists such as anaphylaxis, hives, or respiratory difficulty
• Acute or chronic, clinically significant hematologic, pulmonary, cardiovascular, hepatic renal, and/or other functional abnormality that would jeopardize the health and safety of the participant as determined by the investigator based on medical history, physical examination, laboratory values, and/or diagnostic studies
• A psychiatric illness/social situations that would limit compliance with study requirements as determined by the investigator from the medical history, physical exam, and/or medical record
• Prior or currently active autoimmune disease requiring management with immunosuppression. This includes inflammatory bowel disease, ulcerative colitis, Crohn’s disease, systemic vasculitis, scleroderma, psoriasis, multiple sclerosis, hemolytic anemia, immune-mediated thrombocytopenia, rheumatoid arthritis, systemic lupus erythematosus, Sjogren’s syndrome, sarcoidosis, or other rheumatologic disease or any other medical condition or use of medication (e.g., corticosteroids) which might make it difficult for the patient to complete the full course of treatments or to generate an immune response to vaccines. In the case of asthma or chronic obstructive pulmonary disease taking inhaled corticosteroids that does not require daily systemic corticosteroids is acceptable. Additionally, local acting steroids (topical, inhaled, or intraarticular) will be allowed. Patients on intermittent or short course steroids will be allow if the dose does not exceed 4 mg of dexamethasone (or equivalent) per day for > 7 consecutive days. Any patients receiving steroids should be discussed with the principal investigator (PI) to determine if eligible
• Pregnant and/or breastfeeding
• Known human immunodeficiency virus (HIV)-positive status. These patients are ineligible because of the potential inability to generate an immune response to vaccines.
• STEP 1: Receiving any other investigational agents, or has received an investigational agent within the last 30 days