Trial Investigating an Immunostimulatory Oncolytic Adenovirus for Cancer

Inclusion Criteria: 1. Have histologic or cytologic evidence of colorectal carcinoma (CRC), pancreatic carcinoma (PC), biliary cancer, or epithelial ovarian carcinoma (EOC which may encompass epithelial ovarian, fallopian tube or primary peritoneal carcinoma). 2. Have advanced disease, defined as cancer that is either metastatic or locally advanced, unresectable, and for which radiotherapy or other locoregional therapies are not considered treatment of choice but systemic chemotherapy or no therapy is planned. 3. Have one of the following treatment situations apply: 1. Colorectal carcinoma (CRC) I. A patient with refractory or recurrent metastatic CRC who has either received all conventional therapy; or is entering a "resting" phase between reasonable conventional treatments. II. A patient who is amenable to treatment with LOAd703 plus gemcitabine as a single agent conditioning regimen. 2. Pancreatic cancer I. A patient with either locally advanced, unresectable or metastatic disease who is eligible to receive any line of conventional treatment consisting of gemcitabine and/or nab-paclitaxel. II. A patient who is amenable to treatment with LOAd703 as an "add-on" to standard-of-care gemcitabine-based or nab-paclitaxel- based regimens or gemcitabine or nab-paclitaxel as single agents. c. Biliary cancer I. A patient with either locally advanced unresectable or metastatic biliary cancer who is either treatment-naïve or has received any number of lines of treatment. II. Patient who is amenable to treatment with LOAd703 as an "add-on" to standard-of-care treatment consisting of gemcitabine combined with other agents (e.g. gemcitabine/low-dose cisplatin, gemcitabine/oxaliplatin, etc) in the first line setting or gemcitabine in a combination regimen or as a single agent in latter lines of treatment. d. Ovarian Cancer I. A patient with either epithelial ovarian, fallopian tube or primary peritoneal carcinoma. II. The patient has either: i) Residual disease following first-line standard-of-care combination chemotherapy. ii) Platinum-sensitive disease (platinum free interval ≥ 6 months) in early relapse following first-line standard-of care combination chemotherapy. iii) Platinum-resistant disease and received at least 3 lines of standard treatment. These treatments should have included bevacizumab and/or PARP inhibitors if they are reasonable candidates for such. III. Amenable to treatment with LOAd703 as an "add-on" to standard-of-care paclitaxel-based regimens (excluding bevacizumab), paclitaxel as a single agent, or gemcitabine as a single agent. 4. Have a disease burden that is considered low (i.e. low tumor burden), which is defined on a patient-by-patient basis as per principal investigator's discretion. A rough guideline for defining low tumor burden is that the sum of the product of the bidimensional measurements for all lesions is \< 70 cm2. 5. Have a measurable disease by standard imaging techniques per RECIST criteria. Measurable lesions must be outside of any prior radiation field(s), unless disease progression has been documented at that disease site subsequent to radiation. 6. At least one non-irradiated (or irradiated but disease progression documented at the site subsequent to radiation) lesion must be suitable for image-guided intratumoral injection and needle biopsy. 7. Be medically suited to sedation if required during intratumoral injections. 8. Be at least 18 years-old. 9. Eastern Cooperative Oncology Group (ECOG) performance status 0, 1 or 2. 10. Have no remaining acute toxic effects from previous anticancer therapy \> grade 1 except for any grade of alopecia. 11. Have adequate baseline organ/hematological function, as demonstrated by the following: 1. Absolute neutrophil count (ANC) ≥1.0 x 109/l 2. Hemoglobin ≥9 g/dl 3. Platelet count ≥ 100 x 109/l 4. Bilirubin \< 1.5 times the institutional upper limit of normal (ULN) 5. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) \<2.5 (3, if liver metastases are present) times the institutional ULN. 6. Serum creatinine \<2 times the institutional ULN or calculated creatinine clearance \>35 mL/min 7. Prothrombin (INR)\<1.5 or prothrombin time (PT) \<1.5 ULN; and either partial thromboplastin time or activated partial thromboplastin time (PTT or aPTT) ≤ 1.5 times the ULN. 12. The patient must understand and be willing to provide written informed consent. Exclusion Criteria: 1. Any concurrent treatment that would compromise the study including but not limited to continuous high dose corticosteroids (\>0.5mg/kg), lymphodepleting antibodies or cytotoxic agents. 2. Treatment with high dose immune inhibitors including lymphotoxic monoclonal antibodies such as alemtuzumab (CampathR), or sirolimus (RapamuneR) and its analogs, biological therapy, cytotoxic agents or any investigational agents within 21 days of registration. 3. Ovarian carcinoma patients should not be eligible to PARP inhibitor treatment. 4. Patients on warfarin (or other anti-coagulants) are not eligible. 5. Women who are pregnant, lactating, or planning to become pregnant during the study period, or women of childbearing potential who are not using acceptable contraceptive methods. A woman is considered of childbearing potential if she is not surgically sterile or is less than 1 year since last menstrual period. Acceptable contraceptive methods are: combined (estrogen and progesterone containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal, transdermal), progesterone-only hormonal contraception associated with inhibition of ovulation (oral, injectable, implantable), intrauterine device, intrauterine hormone-releasing system, bilateral tubal occlusion and vasectomized partner. 6. Men who do not consent to the use of condom during intercourse during study participation. 7. Known active hepatitis B or C infection, or HIV infection. 8. Patients with active, severe, autoimmune disease. 9. Uncontrolled intercurrent illness including but not limited to psychiatric illness/social situations that in the opinion of the Investigator would compromise compliance of study requirements or put the patient at unacceptable risk. 10. Other malignancies within the past 2 years (not including basal and squamous cell carcinoma of the skin, localized prostate cancer or in situ cervix carcinoma). 11. Patients must agree to not to vaccinate with living vaccines during participation in the trial.