QUILT-2.022 NANT-008 in Combination w/ 5-fluorouracil, Bevacizumab, Leucovorin & Oxaliplatin in Subjects With Pancreatic Cancer

Exclusion Criteria

• •1. History of previous systemic chemotherapy or investigational therapy.
• •2. History of other active malignancies or brain metastasis except: controlled basal cell carcinoma or squamous cell carcinoma; prior history of in situ cancer (eg, breast, melanoma, squamous cell carcinoma of the skin, cervical) and \> 5 years without evidence of disease; prior history of prostate cancer that is not under active systemic treatment (except hormonal therapy) and with undetectable PSA (\< 0.2 ng/mL).
• •3. Inadequate organ function, evidenced by the following laboratory results:
• •1. White blood cell (WBC) count \< 3,500 cells/mm3
• •2. Absolute neutrophil count \< 1,500 cells/mm3.
• •3. Platelet count \< 100,000 cells/mm3.
• •4. Hemoglobin \< 9 g/dL.
• •5. Total bilirubin greater than the upper limit of normal (ULN) at time of enrollment; unless the subject has known history of Gilbert's syndrome.
• •6. Aspartate aminotransferase (AST \[SGOT\]) or alanine aminotransferase (ALT \[SGPT\]) \> 2.5 × ULN (\> 5 × ULN in subjects with liver metastases).
• •7. Alkaline phosphatase levels \> 2.5 × ULN (\> 5 × ULN in subjects with liver metastases, or \>10 × ULN in subjects with bone metastases).
• •8. Serum creatinine \> 2.0 mg/dL or 177 μmol/L.
• •9. International normalized ratio (INR) or activated partial thromboplastin time (aPTT) or partial thromboplastin time (PTT) \>1.5 × ULN.
• •4. Pre-existing peripheral neuropathy \> grade 1 based on NCI CTCAE V4.03.
• •5. Dihydropyrimidine dehydrogenase gene polymorphism (DPYD\*2A) (must be tested prior to inclusion).
• •6. 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.
• •7. Positive results of screening test for human immunodeficiency virus (HIV), hepatitis B virus (HBV), or hepatitis C virus (HCV).
• •8. Undergone major surgery, other than diagnostic surgery (ie, surgery done to obtain a biopsy for diagnosis without removal of an organ), within 4 weeks prior to day 1 of treatment in this study or surgical wound has not fully healed.
• •9. History of connective tissue disorders (eg, lupus, scleroderma, arteritis nodosa).
• •10. Evidence of gastric ulcers, gastrointestinal fistulas, and gastrointestinal perforations.
• •11. History of interstitial lung disease, history of slowly progressive dyspnea and unproductive cough, sarcoidosis, silicosis, idiopathic pulmonary fibrosis, pulmonary hypersensitivity pneumonitis or multiple allergies that in the opinion of the Investigator may put them at increased risk of interstitial pneumonitis.
• •12. 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.
• •13. Recent history of clinically significant hemoptysis.
• •14. Known hypersensitivity to any component of the study medication(s).
• •15. Pregnant and nursing women.
• •16. Assessed by the investigator to be unable or unwilling to comply with the requirements of the protocol.
• •17. Concurrent or prior use of a strong CYP3A4 inhibitor (including ketoconazole, itraconazole, posaconazole, clarithromycin, indinavir, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin, voriconazole, and grapefruit products) or strong CYP3A4 inducers (including phenytoin, carbamazepine, rifampin, rifabutin, rifapentin, phenobarbital, and St John's Wort) within 14 days before study day 1.
• •18. Concurrent or prior use of a strong CYP2C8 inhibitor (gemfibrozil) or moderate CYP2C8 inducer (rifampin) within 14 days before study day 1.