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