This is a phase 1 open-label study to evaluate the safety and immunogenicity of a neoantigen
DNA vaccine strategy in pancreatic cancer patients following surgical resection and adjuvant
chemotherapy. The neoantigen DNA vaccines will incorporate prioritized neoantigens and
personalized mesothelin epitopes and will be administered with an electroporation device. The
hypothesis of this study is that neoantigen DNA vaccines will be safe and capable of
generating measurable neoantigen-specific CD4 and CD8 T cell responses.
A patient will be eligible for evaluation and sequencing of tissue for vaccine development
only if ALL of the following criteria apply:
- Histologically or cytologically confirmed diagnosis of pancreatic adenocarcinoma;
mixed histology will be included as long as the predominant histology is
- 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.
- Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2
- Normal bone marrow and organ function as defined below:
- white blood cells (WBC) ≥3,000/μL
- absolute neutrophil count ≥1,500/μL
- platelets ≥100,000/μL
- total bilirubin ≤2.5 X institutional upper limit of normal (ULN)
- AST/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
- Able to understand and willing to sign an IRB approved written informed consent
At eligibility recheck prior to vaccination, the above criteria must be met plus:
- Completed adjuvant chemotherapy:
- Initiation of adjuvant chemotherapy within 12 weeks of surgery
- Completion of at least 4 months of adjuvant chemotherapy with
gemcitabine/capecitabine or similar adjuvant chemotherapy at the discretion of
the patient's medical oncologist.
- Additional chemoradiation therapy as recommended by the patient's medical
- Reimaging within 4 weeks of last dose 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
- Neoadjuvant chemotherapy is exclusionary.
- There is a 1 week washout prior to Day 1 of vaccine for patients on daily systemic
steroids at doses exceeding 10 mg prednisone.
- Evidence of neuroendocrine tumor, duodenal adenocarcinoma, or ampullary
- Received neoadjuvant chemotherapy
- 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 or
carcinoma in situ of the cervix.
- Receiving any other investigational agents, or has received an investigational agent
within the last 30 days.
- Known allergy, or history of serious adverse reaction to vaccines 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
- History of syncopal or vasovagal episode as determined by medical record and history
in the 12 month period prior to first vaccination administration.
- Individuals in whom a skinfold measurement of the cutaneous and subcutaneous tissue
for eligible injection sites (left and right medial deltoid region) exceeds 40 mm.
- Individuals in whom the ability to observe possible local reactions at the eligible
injection sites (deltoid region) is, in the opinion of the investigator, unacceptably
obscured due to a physical condition or permanent body art.
- Therapeutic or traumatic metal implant in the skin or muscle of either deltoid region.
- Any chronic or active neurologic disorder, including seizures and epilepsy, excluding
a single febrile seizure as a child.
- Current use of any electronic stimulation device, such as cardiac demand pacemakers,
automatic implantable cardiac defibrillator, nerve stimulators, or deep brain
- 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.