QUILT-3.039: NANT Pancreatic Cancer Vaccine: Combination Immunotherapy in Subjects With Pancreatic Cancer Who Have Progressed on or After Standard-of-care Therapy

Inclusion Criteria:

• Age ≥ 18 years old.
• Able to understand and provide a signed informed consent that fulfills the relevant IRB or IEC guidelines.
• Histologically-confirmed pancreatic cancer with progression on or after SoC therapy.
• ECOG performance status of 0 to 2.
• Have at least 1 measurable lesion and/or non-measurable disease evaluable according to RECIST Version 1.1.
• Must have a recent tumor biopsy specimen following the conclusion of the most recent anti-cancer treatment. If a historic specimen is not available, the subject must be willing to undergo a biopsy during the screening period.
• Must be willing to provide blood samples for exploratory analyses.
• Ability to attend required study visits and return for adequate follow-up, as required by this protocol.
• Agreement to practice effective contraception for female subjects with child-bearing potential and non-sterile males.

Exclusion Criteria:

• History of persistent grade 2 or higher (CTCAE Version 4.03) hematological toxicity resulting from previous therapy.
• History of other active malignancies or brain metastasis except: controlled basal cell carcinoma; prior history of in situ cancer (eg, breast, melanoma, cervical); prior history of prostate cancer that is not under active systemic treatment (except hormonal therapy) and with undetectable prostate-specific antigen (PSA) (< 0.2 ng/mL); bulky (≥ 1.5 cm) disease with metastasis in the central hilar area of the chest and involving the pulmonary vasculature. Subjects with a history of another malignancy must have > 5 years without evidence of disease.
• Serious uncontrolled concomitant disease that would contraindicate the use of the investigational drug used in this study or that would put the subject at high risk for treatment-related complications.
• Systemic autoimmune disease (eg, lupus erythematosus, rheumatoid arthritis, Addison's disease, autoimmune disease associated with lymphoma).
• History of organ transplant requiring immunosuppression.
• History of or active inflammatory bowel disease (eg, Crohn's disease, ulcerative colitis).
• Requires whole blood transfusion to meet eligibility criteria.

• Inadequate organ function, evidenced by the following laboratory results:

  • White blood cell (WBC) count < 3,500 cells/mm3
  • Absolute neutrophil count < 1,500 cells/mm3.
  • Platelet count < 100,000 cells/mm3.
  • Hemoglobin < 9 g/dL.
  • Total bilirubin greater than the upper limit of normal (ULN; unless the subject has documented Gilbert's syndrome).
  • Aspartate aminotransferase (AST [SGOT]) or alanine aminotransferase (ALT [SGPT]) > 2.5 × ULN (> 5 × ULN in subjects with liver metastases).
  • Alkaline phosphatase levels > 2.5 × ULN (> 5 × ULN in subjects with liver metastases, or >10 × ULN in subjects with bone metastases).
  • Serum creatinine > 2.0 mg/dL or 177 μmol/L.
  • International normalized ratio (INR) or activated partial thromboplastin time (aPTT) or partial thromboplastin time (PTT) >1.5 × ULN (unless on therapeutic anti-coagulation).
• Uncontrolled hypertension (systolic > 150 mm Hg and/or diastolic > 100 mm Hg) or clinically significant (ie, active) cardiovascular disease, cerebrovascular accident/stroke, or myocardial infarction within 6 months prior to first study medication; unstable angina; congestive heart failure of New York Heart Association grade 2 or higher; or serious cardiac arrhythmia requiring medication.
• Dyspnea at rest due to complications of advanced malignancy or other disease requiring continuous oxygen therapy.
• Positive results of screening test for human immunodeficiency virus (HIV), hepatitis B virus (HBV), or hepatitis C virus (HCV).
• Current chronic daily treatment (continuous for > 3 months) with systemic corticosteroids (dose equivalent to or greater than 10 mg/day methylprednisolone), excluding inhaled steroids. Short-term steroid use to prevent IV contrast allergic reaction or anaphylaxis in subjects who have known contrast allergies is allowed.
• Known hypersensitivity to any component of the study medication(s).
• Subjects taking any medication(s) (herbal or prescribed) known to have an adverse drug reaction with any of the study medications. See Excluded Medications list.
• Participation in an investigational drug study or history of receiving any investigational treatment within 14 days prior to screening for this study, except for testosterone-lowering therapy in men with prostate cancer.
• Assessed by the investigator to be unable or unwilling to comply with the requirements of the protocol.
• Concurrent participation in any interventional clinical trial.
• Pregnant and nursing women.