Efficacy and Safety Evaluation of EN3348 (Mycobacterial Cell Wall-DNA Complex [MCC]) as Compared With Mitomycin C in the Intravesical Treatment of Subjects With BCG Recurrent/Refractory Non-muscle Invasive Bladder Cancer

Inclusion Criteria:

• Is 18 years of age and older at time of consent signing

• Have either BCG recurrent or refractory NMIBC:

• Refractory disease is defined as evidence of persistent high grade bladder cancer (Ta HG, T1 and/or CIS) at least 6 months from the start of a full inductioncourse of BCG with or without maintenance/re-treatment at 3 months

• Recurrent disease is defined as reappearance of disease after achieving atumor-free status by 6 months following a full induction course of BCG with orwithout maintenance/re-treatment at 3 months. Subjects with recurrent diseasemust have recurred within 18 months following the last dose of BCG

• A full induction course of BCG is defined as at least 5 out of 6 totalexpected instillations of BCG within a period of 2 months, regardless ofdose strength

• Have histologically confirmed NMIBC (according to 2004 WHO classification) within 8weeks prior to randomization

• High grade Ta papillary lesion(s)

• High or low grade T1 papillary lesion(s)(biopsy sample must include evidence ofmuscularis propria)

• CIS, with or without Ta or T1 papillary tumor(s) of any grade

• Have had all visible papillary and resectable CIS lesion(s) removed by TURBT within 8weeks prior to randomization

• Available for the duration of the study including follow-up (approximately 36 months)

• Have an Eastern Cooperative Oncology Group (ECOG) performance status grade of 2 orless

• Have no evidence of urothelial carcinoma involving the upper urinary tract or theurethra (confirmed by extravesical work up, which may include radiological imagingand/or biopsy) within 6 months of randomization:

• If previous work up occurred more than 6 months from randomization, extravesicalwork up must be repeated prior to randomization in order to determine eligibility

• Subjects (male and female) of child-bearing potential (including female subjects whoare post-menopausal for less than 1 year) must be willing to practice effectivecontraception (as defined by the Investigator) during the study and be willing andable to continue contraception for 30 days after their last dose of study treatment

• Is able to understand and give written informed consent

Exclusion Criteria:

• Current or previous history of muscle invasive bladder tumors

• Current or previous history of lymph node positive and/or metastatic bladder cancer

• Current evidence of pure squamous cell carcinoma, pure adenocarcinoma or pureundifferentiated carcinoma of the bladder

• Currently receiving systemic cancer therapy (cytotoxic/cytostatic or immunotherapy)

• Currently receiving treatment with a prohibited therapy

• Current or prior history of systemic lupus erythematosus

• Systemic immunotherapy within 6 months of randomization

• Treatment with an investigational agent within 30 days or 5 half lives fromrandomization, whichever is longer

• Prior treatment with an intravesical chemotherapeutic agent within 3 months ofrandomization except for single perioperative dose of chemotherapy immediatelypost-TURBT

• Prior treatment with EN3348 (MCC) or any other mycobacterial cell wall composition orformulation

• Refractory to mitomycin C (failure to achieve tumor-free status following minimum of a 6 week induction course of mitomycin C)

• Contraindication to mitomycin C

• Untreated urinary tract or bladder infection

• ANC <1000/µL and hemoglobin <10 g/dL

• Known cardiovascular disease such as myocardial infarction within the past 3 months,unstable angina pectoris, congestive heart failure (NYHA Class III or IV) oruncontrolled cardiac arrhythmia

• Female subjects who are pregnant or lactating

• Congenital or acquired immune deficiency

• Have current or history of documented or suspected malignancy of any organ system (diagnosed, treated or untreated) within the past 5 years (with the exception oflocalized transitional cell carcinoma of the ureter treated with ureterectomy ornephroureterectomy, adequately treated basal cell or squamous cell carcinoma of theskin or asymptomatic non-metastatic prostate cancer either previously successfullytreated or currently under active surveillance or receiving hormone therapy only)

• Bladder contracture or history of an inability to retain the instillate for a minimumof 1 hour, even with premedication

• Inability to tolerate intravesical administration or intravesical surgicalmanipulation (cystoscopy or biopsy)

• Clinically significant active infections

• Any medical or psychiatric condition which, in the opinion of the investigator, wouldpreclude the participant from adhering to the protocol or completing the trial perprotocol