University of Kansas Medical Center

Patients who meet all of the following criteria will be eligible to participate in the study: 1. Aged 18 years or older at the time of consent; 2. Able to give informed consent; 3. Has a confirmed histological diagnosis of MPM with histological type epithelioid or biphasic (if biphasic, histology must be predominantly [50%] epithelioid). Histological diagnosis of MPM will be confirmed centrally using specimens or slides from tumor specimens obtained at the time of initial presentation or a subsequent procedure. Central confirmation of diagnosis with immunohistochemistry will be performed, and independent central confirmation will be required for study entry; 4. Measurable disease, per modified Response Evaluation Criteria in Solid Tumors [RECIST] 1.1 (see Section 7) for pleural mesothelioma; 5. Has received a minimum of 1 treatment regimen and a maximum of 2 treatment regimens, which may have been chemotherapeutic and/or immunotherapeutic treatment regimens for MPM which included at least 1 anti-folate and platinum combination regimen; - Adjuvant or neoadjuvant therapy represent 1 line of therapy each; - Patients who have undergone primary surgical resection and/or radiation therapy to the pulmonary site are eligible to participate. For clarity, surgical resection and/or radiation therapy to the pulmonary site are not exclusionary and are not considered a line of therapy; - Treatment that is split between pre-surgical resection and post-surgical resection and is the same regimen will be counted as 1 regimen. Patients meeting this condition should be discussed with the Medical Monitor prior to including the patient in the study; 6. Has a pleural space accessible for IPC or similar device insertion. Patients with a previously inserted IPC or similar device may be enrolled, and the pre-existing IPC or similar device can be used for vector administration as long as it is functional and has no evidence of local infection; 7. Life expectancy 12 weeks in the judgement of the Investigator; 8. Eastern Cooperative Oncology Group (ECOG) status of 1 or 0; 9. Female and male patients: - Female patients of childbearing potential must have a negative pregnancy test upon entry into this study and agree to use a highly effective method of contraception from Screening until 1 month after the last dose of gemcitabine; - Highly effective methods of contraception that result in a low failure rate (i.e., <1% per year) when used consistently and correctly include combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal, or transdermal), progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable, or implantable), intrauterine device, intrauterine hormone-releasing system, bilateral tubal occlusion, vasectomized partner, or sexual abstinence; - True abstinence, when in line with the preferred and usual lifestyle of the patient, is considered a highly effective method only if defined as refraining from heterosexual intercourse during the entire period of study participation and for 1 month after the last dose of gemcitabine. The reliability of sexual abstinence needs to be evaluated in relation to the duration of the clinical study and the preferred and usual lifestyle of the patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, and post-ovulation method) and withdrawal are not acceptable methods of contraception; and - Female patients of non-childbearing potential must be either postmenopausal (no menstrual period for a minimum of 12 months) or surgically sterile upon entry into the study; - Male patients must be either surgically sterile or agree to use a double-barrier contraception method from Screening until 6 months after the last dose of gemcitabine; o Where available and in accordance with local practice, male patients must be advised to seek further advice regarding cryoconservation of sperm prior to gemcitabine treatment due to the possibility of infertility after therapy with gemcitabine; and 10. Adequate laboratory values at Screening: - Hemoglobin 9 g/dL; - White blood cell count 3500/µL; - Absolute neutrophil count 1500/µL; - • Platelet count 100,000/µL; - International normalized ratio (INR) and activated partial thromboplastin time (aPTT) below the upper limit of normal (ULN). It is expected that patients receiving anticoagulation therapy will not have INR and aPTT results that fall within normal limits. It is not intended to exclude these patients and, therefore, medical discretion is permitted for patients who have clinically acceptable results in regards to their current concomitant anticoagulant therapy; - Aspartate aminotransferase (AST) 3 × ULN; - Alanine aminotransferase (ALT) 3 × ULN; - Total bilirubin 2 × ULN; - Estimated glomerular filtration rate (calculated using the Modification of Diet in Renal Disease study equation [see Appendix B]) 50 mL/min/1.73 m2; and - Serum albumin 2.5 g/dL.

Patients who meet any of the following criteria will be excluded from participation in the study: 1. Is "treatment-naïve" (i.e., has not received at least 1 anti-folate and platinum combination regimen); 2. Has previously received 3 or more lines of systemic chemotherapeutic or immunotherapeutic treatment. Treatment that is split between pre-surgical resection and post-surgical resection and is the same regimen will be counted as 1 regimen. Patients meeting this condition should be discussed with the Medical Monitor prior to including the patient in the study; 3. Has previously received treatment with gemcitabine; 4. Has stage IV extrathoracic metastatic disease; 5. Inadequate pulmonary function of clinical significance as per Investigator review; 6. Clinically significant pericardial effusion (i.e., as judged by the Investigator and/or requiring drainage) detected by computed tomography (CT) scan at Screening. Standard of care CT scans completed within 2 weeks prior to Screening may be used in place of the Screening CT scan on a case by-case basis as agreed with the Medical Monitor; 7. Prior therapy(ies), if applicable, must be completed according to the criteria below prior to vector administration: - Cytotoxic chemotherapy, at least 21 days from last dose; - Non-cytotoxic chemotherapy (e.g., small molecule inhibitor), at least 14 days from last dose; - Monoclonal antibody, at least 30 days from last dose; - Non-antibody immunotherapy (e.g., tumor vaccine), at least 42 days from last dose; - Radiotherapy, at least 14 days from last local site radiotherapy; - Hematopoietic growth factor, at least 14 days from last dose; or - Study drug, 30 days or 5 half-lives, whichever is longer, from last dose; 8. Patient previously treated with IFNs (e.g., for chronic active hepatitis); 9. Suspected/known hypersensitivity to IFN-α2b or rAd-IFN (including any of its excipients); 10. Known hypersensitivity to celecoxib (including any of its excipients) or sulfonamides; 11. Known hypersensitivity to gemcitabine (including any of its excipients); 12. Impaired cardiac function or clinically significant cardiac disease including the following: - New York Heart Association class III or IV congestive heart failure; - Myocardial infarction within the last 12 months; and - Patients known to have impaired left ventricular ejection fraction per institutional standards and of clinical significance as per Investigator review; 13. Women who are pregnant or breastfeeding; 14. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, depression, or psychiatric illness/social situations within the last 12 months; 15. Patients with active, known, or suspected auto-immune disease or a syndrome that requires systemic or immunosuppressive agents (oral prednisolone or equivalent at a dose of 10 mg per day is permitted); NOTE: patients with vitiligo, residual hypothyroidism due to auto immune disease only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll; 16. History of asthma, acute rhinitis, nasal polyps, angioneurotic edema, urticaria, or other allergic type reactions after taking acetylsalicylic acid or NSAIDs, including COX-2 inhibitors; 17. History of ulcer disease or gastrointestinal bleeding; 18. Uncontrolled or poorly controlled hypertension (i.e., blood pressure >160/100 mmHg) requiring 3 or more anti-hypertensive drugs; 19. Heart rate corrected QT interval using Fridericia's formula >470 ms on resting 12-lead electrocardiogram (ECG); 20. Patients receiving lithium; 21. Any significant disease which, in the opinion of the Investigator, would place the patient at increased risk of harm if he/she participated in the study; 22. History of a prior malignancy for which treatment was completed <2 years prior to Screening or for which the patient has continued evidence of disease, or concurrent malignancy that is clinically unstable and requires tumor-directed treatment; 23. Has a congenital or acquired immunodeficiency, including patients with known history of infection with human immunodeficiency virus; 24. Has both serum albumin 2.5 to 3.5 g/dL and total bilirubin >1.5 ULN; 25. History of clinically significant inflammatory bowel disease requiring systemic (parenteral) immunosuppressive therapy within 5 years prior to Screening; or 26. History of galactose intolerance, Lapp lactase deficiency, or glucose-galactose malabsorption.