LOAd703 Oncolytic Virus Therapy for Pancreatic Cancer

Inclusion Criteria:

1. Diagnosis of ductal adenocarcinoma of the pancreas (PDAC).
2. Low tumor burden with at least one lesion that is suitable for image-guided intratumoral injection and needle biopsy.
3. The patient is not eligible for a complete surgical resection of their disease as evaluated by a radiologist and/or surgeon.
4. Patients who may receive the injections endoscopically should be eligible for sedation.
5. The patient must be eligible for standard of care treatment with gemcitabine +nab-paclitaxel.
6. Age ≥ 18 yrs of age
7. Females of childbearing potential must have a negative pregnancy test and agree to use contraception during on-study protocol treatment.
8. Eastern Cooperative Oncology Group (ECOG) performance status 0, 1 or 2.
9. Absolute neutrophil count (ANC) ≥1.0 x 10\^9/l, hemoglobin ≥9 g/dl, platelet count ≥ 100 x 10\^9/l, prothrombin (INR) \<1.5.
10. Adequate hepatic function, with bilirubin \< 1.5 x the ULN, and AST and ALT \< 2.5 x ULN
11. Adequate renal function with serum creatinine \<2 x the ULN or creatinine clearance \>30 mL/min
12. The patient must provide informed consent.

Exclusion Criteria:

1. Any concurrent treatment that would compromise the study including but not limited to continuous high dose corticosteroids (\>10 mg/day of prednisone equivalence), lymphodepleting antibodies or cytotoxic agents.
2. Treatment with high dose immune inhibitors including lymphotoxic monoclonal antibodies such as alemtuzumab (Campath), or rapamycin/rapalogs or cytotoxic agents within 21 days of registration
3. Treatment with biologic therapy within 21 days of registration.
4. Use of any investigational agents within 21 days of registration.
5. The use of systemic immunostimulatory agents (including, but not limited to, interferons and IL-2) are prohibited within 4 weeks or 5 half-lives of the drug (whichever is longer) prior to initiation of study treatment and during study treatment because these agents could potentially increase the risk for autoimmune conditions when given in combination with atezolizumab
6. Pregnant or breastfeeding females.
7. Known active hepatitis B or C infection, HIV infection or tuberculosis.
8. Patients with active autoimmune disease or immune deficiency or previous Guillain-Barre syndrome. Patients with eczema, psoriasis, lichen simplex chronicus or vitiligo with dermatologic manifestations only (e.g. patients with psoriatic arthritis are excluded) are eligible for the study provide all of the following conditions are met:

   * Rash must cover \<10% of body surface area
   * Disease is well controlled at baseline and requires only low-potency topical corticosteroids
   * No occurrence of acute exacerbations of the underlying condition requiring psoralen plus ultraviolet A radiation, methotrexate, retinoids, biologic agents, oral calcineurin inhibitors or high-potency or oral corticosteroids within the previous 12 months
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 cell carcinoma of the skin, prostate cancer or in situ cervix carcinoma).
11. Moderate to large volume ascites.
12. History of leptomeningeal disease.
13. Uncontrolled pleural effusion, pericardial effusion or ascites requiring recurrent drainage procedures (once monthly or more frequently)
14. History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g. bronchiolitis obliterans), drug-induced pneumonitis, or idiopathic pneumonitis or evidence of active pneumonitis on screening chest computed tomography (CT) scan. However, history of radiation pneumonitis in the radiation field (fibrosis) is permitted.
15. Unstable angina, uncontrolled cardiac arrhythmia, recent (within 3 months) history of myocardial infarction or stroke or New York Class III/IV congestive heart failure
16. Major surgical procedure, other than for diagnosis, within 4 weeks prior to initiation of study treatment or anticipation of need for a major surgical procedure during the study.
17. Prior allogeneic stem cell or solid organ transplantation.
18. History of severe allergic anaphylactic reactions to chimeric human or humanized antibodies or fusion proteins.
19. Known hypersensitivity to CHO cell products or any component of the atezolizumab formulation.
20. Live attenuated vaccines (e.g. FluMist) are prohibited within 4 weeks prior to initiation of study treatment, during atezolizumab treatment, and for 5 months after the final dose of atezolizumab.
21. Adenovirus-based vaccines (e.g Vaxzevria, known as COVID-19 vaccine Astra Zeneca, J\&J Covid-19 vaccine) are prohibited 3 months prior to initation of study treatment, during treatment and 6 months after the final dose of LOAd703