Talimogene Laherparepvec in Patients With Unresectable Pancreatic Cancer

Inclusion Criteria: * cytological or histological proof of adenocarcinoma of the pancreas * unresectable, locally advanced disease (isolated liver metastases are permitted) * tumors of at least 1 cm diameter at screening * measurable disease using Response Evaluation Criteria In Solid Tumors (RECIST) criteria * failure of either standard therapy, OR any one of the following: * no alternative therapeutic of higher curative potential is available; * investigator determination that patient could not tolerate alternative therapeutic due to unacceptable toxicity; or, * patient refusal to be treated with available alternative therapeutic * age \> 18 years * life expectancy \> 3 months * adequate bone marrow function as indicated by: * White blood cells (WBC) ≥ 3.0 x 10\^9/L * platelets ≥ 100 x 10\^9/L * hemoglobin ≥ 8.5 gm/dL * adequate liver function as indicated by: * bilirubin \< 1.5 x upper limit of normal (ULN) * alanine aminotransferase (ALT) or aspartate aminotransferase (AST) \< 5 x ULN in case of presence of liver metastasis * ALT or AST \< 2.5 x ULN in case of absence of liver metastasis * adequate renal function as indicated by a serum creatinine level \< 1.5 x ULN. * adequate hemostasis indicated by international normalized ratio (INR) ≤ 1.5 * mentally, physically and geographically able to undergo treatment and follow-up * provided written informed consent * first patient in each cohort only: seropositive for herpes simplex virus type 1 (HSV1) Exclusion Criteria: * history of other malignancy within two years prior to screening, except for prostate cancer (T1c, T2ab with definitive treatment, prostate-specific antigen (PSA) \< 1 ng/ml, and without ongoing hormone suppression) or adequately treated in situ carcinoma of the cervix, basal cell carcinoma, or squamous cell carcinoma of the skin * cystic form of pancreatic cancer; microcystic disease may be eligible upon discussion with Medical Monitor * Common Terminology Criteria for Adverse Events (CTCAE) version 3 grade 2 or greater clinical pancreatitis within 8 weeks prior to dosing with OncoVEX\^GM-CSF * other than metastases limited to the liver, imaging evidence of metastatic disease to any other organ or tissue * any serious concomitant systemic disorder that would compromise the safety of the patient, at the discretion of the investigator * evidence of compromised immune function including but not limited to: * clinically significant absolute lymphocyte count \< Lower Limit of Normal (LLN) * known human immunodeficiency virus (HIV), acute or chronic active hepatitis B, or hepatitis C infection; * concurrently taking HIV antiviral medications (e.g. protease inhibitors, azidothymidine, etc.) * received intravenous (IV), intramuscular (IM) or subcutaneous (SC) human gamma globulin within 6 months prior to dosing with OncoVEX\^GM-CSF * patients taking immunosuppressive agents (e.g. cyclosporine, tacrolimus, or oral or systemic corticosteroids at a dose of \> 10 mg/day of prednisone or equivalent). * pregnancy, lactation or lack of effective contraception in women of child-bearing potential (e.g., not post menopausal for \> 2 years, or had tubal ligation); lack of effective contraception in men if the partner is of child-bearing potential; women must have been practicing an effective contraceptive method for at least three months prior to entry in to the trial (hormonal contraception or intrauterine device in conjunction with a barrier method); men must use a condom or be surgically sterilized * patients with active bacterial or viral infections that require treatment with systemic antibiotics or antiviral agents within 2 weeks prior to the first dose of OncoVEX\^GM-CSF); (note: patients with active cold sores or other HSV1 infections must wait until those lesions have crusted over before receiving OncoVEX\^GM-CSF) * surgery requiring general or spinal anesthesia within four weeks prior to dosing with OncoVEX\^GM-CSF * Treatment with an investigational agent within 4 weeks prior to the first dose of OncoVEX\^GM-CSF * serum carbohydrate antigen (CA)19.9 levels \> 3000 U/mL at screening * evidence of ascites on screening abdominal computed tomography (CT) scan