Inclusion Criteria:

1. Aged 18 years or older at the time of consent
2. Able to give informed consent
3. Have, at entry, confirmed by a pathology report: Carcinoma in Situ (CIS) only; Ta/T1 high grade disease with concomitant CIS or Ta/T1 high grade disease without concomitant CIS
4. Are "BCG Unresponsive" which refers to patients with high grade NMIBC who are unlikely to benefit from and who will not receive further intravesical BCG. The term "BCG unresponsive" includes patients who did not respond to BCG treatment and have a persistent high grade recurrence within 12 months after BCG was initiated, and those who despite an initial complete response (CR) to BCG, relapse with high grade NMIBC within 12 months of their last intravesical treatment with BCG. The following criteria define the patients who may be included in the study:
   • Have received at least 2 previous courses of BCG within a 12 month period - defined as at least 5 of 6 induction BCG instillations and at least 2 out of 3 instillations of maintenance BCG, or at least two of six instillations of a second induction course, where maintenance BCG is not given
     • Exception: those who have T1 high grade disease at first evaluation after induction BCG alone (at least 5 of 6 doses) may qualify in the absence of disease progression
   • At the time of tumor recurrence, patients with CIS alone or high grade Ta/T1 with CIS should be within 12 months of last exposure to BCG and patients with Ta/T1 without CIS should be within 6 months of last exposure to BCG
   • No maximum limit to the amount of BCG administered
   • All visible papillary tumors must be resected and those with persistent T1 disease on transurethral resection of bladder tumor (TURBT) should undergo an additional re-TURBT within 14 to 60 days prior to beginning study treatment. Obvious areas of CIS should also be fulgurated.
5. Available for the whole duration of the study
6. Life expectancy >2 years, in the opinion of the investigator
7. Eastern Cooperative Oncology Group (ECOG) status 2 or less
8. Absence of concomitant upper tract urothelial carcinoma or urothelial carcinoma within the prostatic urethra. Freedom from upper tract disease (if clinically indicated) as indicated by no evidence of upper tract tumor by either intravenous pyelogram, retrograde pyelogram, computed tomography (CT) scan with or without urogram, or MRI with or without urogram performed within 6 months of enrollment
9. Patients with prostate cancer on active surveillance at low risk for progression, defined as Prostate-Specific Antigen (PSA) < 10 ng/dL, Gleason score 6 and clinical stage tumor-1 (cT1) are permitted to be in the study at the discretion of the investigator (see exclusion criteria 10).
10. Female patients of childbearing potential must use maximally effective birth control during the period of therapy, must be willing to use contraception for 1 month following the last study drug infusion and must have a negative urine or serum pregnancy test upon entry into this study. Otherwise, female patients must be postmenopausal (no menstrual period for a minimum of 12 months) or surgically sterile. 'Maximally effective birth control' means that the patient, if sexually active, should be using a combination of two methods of birth control that are approved and recognized to be effective by Regulatory Agencies
11. Male patients must be surgically sterile or willing to use a double barrier contraception method upon enrollment, during the course of the study, and for 1 month following the last study drug infusion
12. Adequate lab values

Exclusion Criteria:

1. Current or previous evidence of muscle invasive (muscularis propria) or metastatic disease present at the time of screening. Examples that increase the risk of metastatic disease are (but not limited to):
   • Presence of lymphovascular invasion and/micropapillary disease as shown in the histology of the biopsy sample
   • Patients with T1 disease accompanied by the presence of hydronephrosis
2. Current systemic therapy for bladder cancer
3. Current or prior pelvic external beam radiotherapy within 5 years of entry
4. Prior treatment with adenovirus-based drugs
5. Suspected hypersensitivity to IFN alfa2b
6. Symptomatic urinary tract infection or bacterial cystitis (once satisfactorily treated, patients can enter the study)
7. Clinically significant and unexplained elevated liver or renal function tests
8. Women who are pregnant or lactating or refuse to commit to use contraception anytime during the study
9. Any other significant disease or clinical findings which in the opinion of the investigator would prevent study entry
10. History of malignancy of other organ system within past 5 years, except treated basal cell carcinoma or squamous cell carcinoma of the skin and ≤ pathological tumor-2 (pT2) upper tract urothelial carcinoma at least 24 months after nephroureterectomy. Also patients with genitourinary cancers other than urothelial cancer or prostate cancer that are under active surveillance are excluded (see inclusion criterion 9)
11. Patients who cannot hold instillation for 1 hour
12. Patients who cannot tolerate intravesical dosing or intravesical surgical manipulation
13. Intravesical therapy within 8 weeks prior to beginning study treatment with the exception of:
    • cytotoxic agents (e.g. Mitomycin C, doxorubicin and epirubicin) when administered as a single instillation immediately following a TURBT procedure which is permitted up to 14 to 60 days prior to beginning study treatment
    • previous intravesical BCG therapy, which can be given at least 5 weeks before the diagnostic biopsy required for entry into the study