Inclusion Criteria:

1. Aged 18 years or older at the time of consent
2. Able to give informed consent

3. Subjects with high grade BCG-refractory or relapsed NMIBC including

   • High grade non-invasive papillary carcinomas (Ta) and subjects with high grade tumors that invade sub-epithelial connective tissue (T1) or
   • Carcinoma in situ (CIS) only or
   • CIS and Ta or T1 tumors Refractory is defined as failure to achieve a disease-free state at six months after adequate induction of BCG therapy with either maintenance or re-induction at 3 months. Adequate induction is defined as a minimum of 5 out of 6 induction doses and adequate maintenance is defined as a minimum of 2 out of 3 doses of treatment.

   Relapse is defined as recurrence within 1 year after a complete response to BCG treatment

4. Complete resection of visible papillary lesions or CIS by TURBT or endoscopic resection between 14 and 60 days prior to beginning study treatment
5. Available for the whole duration of the study
6. Life expectancy >2 years, in the opinion of the investigator
7. ECOG status 2 or less
8. Absence of upper tract urothelial carcinoma
9. Female subjects 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 subjects must be postmenopausal (no menstrual period for a minimum of 12 months) or surgically sterile.
10. Male subjects 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.

11. Adequate laboratory values.

    • Hemoglobin ≥10 g/dL.
    • WBC ≥4000/μL.
    • ANC ≥2000/μL.
    • Platelet count ≥100,000/μL.
    • INR within institutional normal limits.
    • aPTT within institutional normal limits.
    • AST ≤1.5 x ULN.
    • ALT ≤1.5 x ULN.
    • Total bilirubin within institutional normal limits.
    • Creatinine ≤1.5 x ULN.

Exclusion Criteria:

1. Current or previous evidence of muscle invasive or metastatic disease
2. Current systemic therapy for bladder cancer
3. Current or prior pelvic external beam radiotherapy
4. Prior treatment with adenovirus-based drugs
5. Suspected hypersensitivity to interferon alpha
6. Existing urinary tract infection or bacterial cystitis
7. Clinically significant and unexplained elevated liver or renal function tests
8. Women who are pregnant or lactating
9. Severe cardiovascular disease
10. History of malignancy of other organ system within past 5 years (except treated basal cell carcinoma or squamous cell carcinoma of the skin)
11. Subjects who cannot hold instillation for 1 hour
12. Subjects who cannot tolerate intravesical dosing or intravesical surgical manipulation
13. Intravesical therapy within 6 weeks of enrollment