Neoantigen Peptide Vaccine Strategy in Pancreatic Cancer Patients Following Surgical Resection and Adjuvant Chemotherapy
Condition: Pancreas Cancer; Pancreatic Cancer; Cancer of the Pancreas
MeSH terms: Pancreatic Neoplasms
Intervention: Neoantigen Peptide Vaccine; Poly ICLC; Blood for immune monitoring
Intervention description: • Each pool of vaccine study drug + poly IC:LC will be administered to one of the four limbs (A - Right Arm, B - Left Arm, C - Right Leg, D - Left Leg) by subcutaneous (SC) injection.; • Each pool of vaccine study drug + poly IC:LC will be administered to one of the four limbs (A - Right Arm, B - Left Arm, C - Right Leg, D - Left Leg) by subcutaneous (SC) injection.; -Baseline, day 1, day 22, day 50, day 78, week 25, and week 73
Intervention MeSH terms: Poly I-C; Carboxymethylcellulose Sodium; Poly ICLC
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 12.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This is a phase 1 open-label study to evaluate the safety and immunogenicity of a neoantigen
      peptide vaccine strategy in pancreatic cancer patients following surgical resection and
      adjuvant chemotherapy. The neoantigen peptide vaccines will incorporate prioritized
      neoantigens and personalized mesothelin epitopes and will be co-administered with poly-ICLC.
      The hypothesis of this study is that neoantigen peptide vaccines will be safe and capable of
      generating measurable neoantigen-specific CD4 and CD8 T cell responses.
    

Eligibility criteria:

        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 FFPE blocks.

          -  At least 18 years of age.

          -  Life expectancy of > 12 months.

          -  ECOG performance status ≤ 2

          -  Normal bone marrow and organ function as defined below:

               -  WBC>=3,000/μL

               -  absolute neutrophil count>=1,500/μL

               -  platelets>=100,000/μL

               -  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 ULN)

               -  AST≤ 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.

             9-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 IRB approved written informed consent
             document.

        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 LCIS/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, Sjögren'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 PI to determine if eligible.

          -  Pregnant and/or breastfeeding.

          -  Known HIV-positive status. These patients are ineligible because of the potential
             inability to generate an immune response to vaccines.